Manufacturing of small film strips
47 claims: 27 independent, 20 dependent
- 1複数の個々のフィルム生成物を形成する方法であって、(a)フィルム形成マトリックスを入れる容器を提供するステップと、(b)前記容器に 接続されている 複数の個々の容積測定ポンプを提供するステップと、(c)複数のオリフィス を含むマニホールド を提供するステップであり、 マニホールドは、第1の側及び第2の側を有し、各オリフィスは、マニホールドの第1の側からマニホールドの第2の側まで延びており、 各オリフィスが それ自身の 個々の容積測定ポンプ である前記容積測定ポンプの1つとマニホールドの第1の側上で流体接続している ステップと、(d)前記容器から前記個々の容積測定ポンプまで前記フィルム形成マトリックスを供給するステップと、 その後、 (e)前記 個々の 容積測定ポンプのそれぞれから、該ポンプ と流体接続している オリフィスを通して マニホールドの第1の側からマニホールドの第2の側まで 所定の量の前記フィルム形成マトリックスを分配するステップと、 その後、 (f) 前記オリフィスのそれぞれから 複数の個々の湿潤フィルム生成物を基材上に 直接堆積 す る ステップとを含む方法。
- 2前記基材がバッキングフィルムである、請求項1に記載の方法。
- 3前記基材が、前記複数のオリフィスから乾燥器まで第1の方向に動く、請求項1に記載の方法。
- 4前記基材が、前記複数のオリフィスから乾燥器まで第1の方向に連続して動かされる、請求項1に記載の方法。
- 5ステップ(d)から(f)が繰り返される、請求項1に記載の方法。
- 6前記個々の湿潤フィルム生成物が前記基材の領域上に押し出され、前記領域には、すでに押し出された個々の湿潤フィルム生成物はない、請求項5に記載の方法。
- 7前記個々の容積測定ポンプのそれぞれが、1回の行程あたり4マイクロリットルから250マイクロリットルを分配する、請求項1に記載の方法。
- 8前記フィルム形成マトリックスが少なくとも25%固形である、請求項1に記載の方法。
- 9(g)前記複数の個々の湿潤フィルム生成物を乾燥して、複数の乾燥した個々のフィルム生成物を形成するステップをさらに含む、請求項1に記載の方法。
- 10前記複数の乾燥した個々のフィルム生成物がダイカットされる、請求項 9 に記載の方法。
- 11前記個々の容積測定ポンプがピストンポンプである、請求項1に記載の方法。
- 12前記個々の容積測定ポンプが、可変速度のピストンポンプである、請求項1に記載の方法。
- 13前記個々の容積測定ポンプが、可変行程のピストンポンプである、請求項1に記載の方法。
- 14前記個々の容積測定ポンプが複式ピストンポンプである、請求項1に記載の方法。
- 15前記オリフィスのそれぞれがスロットダイである、請求項1に記載の方法。
- 16前記個々の湿潤フィルム生成物のそれぞれが、各個々の湿潤フィルム生成物に関して均一の含有量を有する、請求項1に記載の方法。
- 17複数の個々のフィルム細片を形成する方法であって、(a)フィルム形成マトリックスを入れる容器を提供するステップと、(b)前記容器に 接続されている 複数の個々の計量ポンプを提供するステップと、(c)複数のオリフィス を含むマニホールド を提供するステップであり、 マニホールドは、第1の側及び第2の側を有し、各オリフィスは、マニホールドの第1の側からマニホールドの第2の側まで延びており、 各オリフィスが それ自身の 個々の計量ポンプ である前記容積測定ポンプの1つとマニホールドの第1の側上で流体接続している ステップと、(d)前記容器から前記複数の個々の計量ポンプまで前記フィルム形成マトリックスを供給するステップと、 その後、 (e)前記 個々の 計量ポンプのそれぞれから、該ポンプ と流体接続している オリフィスを通して所定の量の前記フィルム形成マトリックスを分配するステップと、 その後、 (f) 前記オリフィスのそれぞれから 複数の個々の湿潤フィルム細片を基材上に 直接堆積 す る ステップとを含む方法。
- 18前記基材がバッキングフィルムである、請求項 17 に記載の方法。
- 19前記基材が、前記複数のオリフィスから乾燥器まで第1の方向に連続して動かされる、請求項 17 に記載の方法。
- 20前記個々の湿潤フィルム細片が前記基材の領域上に押し出され、前記領域には、すでに押し出された湿潤フィルム細片はない、請求項 17 に記載の方法。
- 21前記フィルム形成マトリックスが少なくとも25%固形である、請求項 17 に記載の方法。
- 22(g)複数の乾燥した個々のフィルム細片を形成するために、前記個々の湿潤フィルム細片を乾燥させるステップをさらに含む、請求項 17 に記載の方法。
- 23少なくとも1つの乾燥した個々のフィルム細片が、将来的な使用のために巻かれる及び保管される、請求項 22 に記載の方法。
- 24少なくとも1つの乾燥した個々のフィルム細片を、個々のフィルム生成物に切断することができる、請求項 22 に記載の方法。
- 25前記オリフィスのそれぞれがスロットダイである、請求項 17 に記載の方法。
- 26前記個々の湿潤フィルム細片のそれぞれが、前記基材上で細い一片に押し出される、請求項 17 に記載の方法。
- 27前記個々の湿潤フィルム細片のそれぞれが、各個々の湿潤フィルム細片に関して均一の含有量を有する、請求項 17 に記載の方法。
- 28複数の個々のフィルム生成物を形成するための装置であって、(a)フィルム形成マトリックスを入れるための容器と、(b)前記容器に 接続されている 複数の個々の容積測定ポンプと、(c)複数のオリフィス を含むマニホールド であり、 マニホールドは、第1の側及び第2の側を有し、各オリフィスは、マニホールドの第1の側からマニホールドの第2の側まで延びており、 各オリフィスが それ自身の個々の 容積測定ポンプ である前記容積測定ポンプの1つとマニホールドの第1の側上で流体接続している オリフィスと、(d)基材と、(e)前記装置に通して前記基材を動かすための手段とを含む装置。
- 29前記容器が加圧される、請求項 28 に記載の装置。
- 30前記個々の容積測定ポンプが、回転ピストンポンプである、請求項 28 に記載の装置。
- 31各個々の容積測定ポンプが、1つの行程あたり4マイクロリットルから250マイクロリットル放出する、請求項 28 に記載の装置。
- 32各個々の容積測定ポンプが、可変行程能力を有する、請求項 28 に記載の装置。
- 33各個々の容積測定ポンプが、可変速度能力を有する、請求項 28 に記載の装置。
- 34前記個々のフィルム生成物が小さいフィルム生成物である、請求項 28 に記載の装置。
- 35乾燥器をさらに含む、請求項 28 に記載の装置。
- 36前記オリフィスの前記それぞれがスロットダイである、請求項 28 に記載の装置。
- 37複数の個々のフィルムパッチを形成する方法であって、(a)溶解可能な高分子材料 を含む シートを含む基材を提供するステップであり、前記シートは上面を有し、前記基材は第1の方向に連続して動くステップと、(b)湿潤フィルム形成マトリックスを入れる容器を提供するステップであり、前記湿潤フィルム形成マトリックスが第2の高分子材料及び有効成分を含むステップと、(c)前記容器 接続されている 複数の個々の容積測定ポンプを提供するステップと、(d)複数のオリフィス を含むマニホールド を提供するステップであり、 マニホールドは、第1の側及び第2の側を有し、各オリフィスは、マニホールドの第1の側からマニホールドの第2の側まで延びており、 各オリフィスが それ自身の 個々の容積測定ポンプ である前記容積測定ポンプの1つとマニホールドの第1の側上で流体接続しており 、各オリフィスが隙間によって互いから離されるステップと、(e)前記容器から前記個々の容積測定ポンプまで前記湿潤フィルム形成マトリックスを供給するステップと、 その後、 (f)前記 個々の 容積測定ポンプのそれぞれから、該ポンプ と流体接続している オリフィスを通して マニホールドの第1の側からマニホールドの第2の側まで 所定の量の前記フィルム形成マトリックスを分配するステップと、 その後、 (g)複数の湿潤フィルム生成物を形成するために、 前記オリフィスのそれぞれから 前記所定の量の前記湿潤フィルム形成マトリックスを前記シートの前記上面に 直接堆積 す る ステップと、(h)前記シートを含む第1の層及び乾燥したフィルム生成物を含む第2の層を含む複数の複層のフィルムパッチを形成するために、前記湿潤フィルム生成物を乾燥させるステップとを含む方法。
- 38ステップ(e)から(g)が繰り返される、請求項 37 に記載の方法。
- 39前記第1の層が前記第2の層よりも遅い溶解速度を有する、請求項 37 に記載の方法。
- 40(i)前記第1の層を切断して個々のフィルムパッチを提供するステップであって、前記個々のフィルムパッチが1つの乾燥したフィルム生成物を含むステップをさらに含む、請求項 37 に記載の方法。
- 41前記個々のフィルムパッチの前記第1の層の前記上面が、前記第2の層よりも大きい幅又は大きい長さを有し、前記第1の層の前記上面の少なくとも一部が前記第2の層と接触していない、請求項 40 に記載の方法。
- 42個々の乾燥したフィルム生成物のそれぞれが、1000mg以下の重量である請求項9記載の方法。
- 43個々の湿潤フィルム生成物のそれぞれが、2000mg以下の重量である請求項1記載の方法。
- 44個々の乾燥したフィルム生成物のそれぞれが、1000mg以下の重量である請求項22記載の方法。
- 45個々の湿潤フィルム生成物のそれぞれが、2000mg以下の重量である請求項17記載の方法。
- 46個々の乾燥したフィルム生成物のそれぞれが、1000mg以下の重量である請求項37記載の方法。
- 47個々の湿潤フィルム生成物のそれぞれが、2000mg以下の重量である請求項37記載の方法。
Independent claims47
71 paragraphs, as filed
The present invention relates to a film forming method. In particular, the present invention relates to the formation of films, especially small film strips, on a substrate by the use of individual pumps.
The use of films in the administration of active ingredients such as medicines, cosmetics and other materials is becoming more and more popular. Such films must have a fairly uniform size and a substantially uniform dispersion of components. Substantially uniform dispersion of the ingredients is crucial to ensure the correct dose if the film contains pharmaceutical ingredients. The film can be formed into the desired shape, and in some cases it may be useful to form the film on the surface of the substrate. Forming a film using a substrate not only facilitates processing, but can also be useful for packaging film products. Generally, the wet film forming matrix is deposited on the surface of the substrate and then dried to form the resulting film, which is then sized and cut into individual film strip products. Unfortunately, however, such a general process results in a large amount of waste film due to the dimensioning and cutting process. In addition, conventional machining methods utilize a single pump mechanism with multiple slot dies or other orifices. Such a method tends to feed the wet film forming matrix non-uniformly through the orifice, resulting in an irregular and non-uniform formulation. Moreover, in the case of film matrices with high solid or particle content, the orifices may tend to block. The use of one pump mechanism for multiple orifices results in a large amount of film forming matrix being supplied to a particular orifice without providing sufficient pressure to open the closed orifice. Therefore, the end result of such conventional processing is a non-uniform administration and a product lacking in compositional uniformity.
<p num="0003"> The present invention solves the problems caused by conventional film processing by providing, for example, a method for continuously producing a film product without having to measure the dimensions of the film product and simultaneously supplying a uniform film preparation. It is a thing.</p>
<p num="0004"> In one embodiment of the invention, a method of forming a plurality of individual film products is provided, the method relating to (a) a step of providing a container containing a film forming matrix and (b) a container. A step of providing multiple individual volumetric pumps, (c) a step of providing multiple orifices, each of which is associated with an individual volumetric pump, and (d) film formation from a container. The steps of supplying the matrix to the individual volumetric pumps, (e) distributing a predetermined amount of film-forming matrix from each of the volumetric pumps through the associated orifice, and (f) individually on the substrate. Including the step of extruding the wet film product of. Another aspect of the invention provides a method of forming a plurality of individual film strips, the method being associated with (a) a step of providing a vessel containing a film forming matrix and (b) a vessel. A step of providing multiple individual weighing pumps, (c) a step of providing multiple orifices, each orifice associated with an individual weighing pump, and (d) a plurality of film forming matrices from a container. The steps of feeding the individual volumetric pumps, (e) distributing a predetermined amount of film-forming matrix from each of the metering pumps through its associated orifices, and (f) individual wetting on the substrate through the orifices. It may include the step of extruding a piece of film.</p><p num="0005"> In another aspect of the invention, an apparatus is provided for forming a plurality of individual film products, the apparatus comprising a container for containing a film forming matrix and a plurality of individual volumetric measurements associated with the container. It includes a pump, a plurality of orifices, each of which is associated with a volumetric pump, a substrate, and a means of moving the substrate through the device. In yet another aspect of the invention, a plurality of individual film patches. A method of forming a patch) is provided, which is (a) a step of providing a substrate containing a first polymer material, in which the substrate moves continuously in the first direction. The step of having the upper surface of the base material and (b) the step of providing a container for containing the film forming matrix, in which the film forming matrix contains the second polymer material and the active ingredient, are associated with (c) the container. A step of providing a plurality of individual volumetric measuring pumps and (d) a step of providing a plurality of orifices, each orifice being associated with an individual volumetric measuring pump, and each orifice being separated by a gap. Steps, (e) supplying the film forming matrix from the vessel to the individual volumetric pumps, and (f) distributing a predetermined amount of film forming matrix from each of the volumetric pumps through its associated orifice. And (g) as the substrate moves in the first direction, a predetermined amount of film-forming matrix is extruded onto the top surface of the substrate to form multiple individual wet film products, and (h) individual It comprises the step of drying the wet film product to form a plurality of patches containing a layer of a first substrate and a layer of a second dried film product.</p>
<figref num="1">Represents one aspect of the invention in which individual film products can be formed.</figref><figref num="2">Represents a second aspect of the invention in which individual film strips can be formed.</figref><figref num="3">Figures 3A and 3B represent film patches formed by other aspects of the invention.</figref><figref num="4">Represents a further aspect of the invention in which a substrate and a plurality of individual film products can be formed on the surface of the substrate.</figref>
(Detailed description of the invention) The present invention relates to methods and devices designed for the formation of film products, and also to film products containing at least one active composition. In particular, the present invention relates to a method of forming a film product on a substrate while maintaining the uniformity and structural integrity of the components of the individual film products. In addition, the present invention provides methods and devices for forming film products that minimize the amount of waste normally unavoidable in film processing. The film system embodies a technical field that has major advantages in the field of administration of drugs, drugs and various other active ingredients, as well as drug delivery systems to individuals in need thereof. The processing and production of film strips and the technology of thin films are technically difficult and cumbersome in order to provide the desired final product exhibiting advantageous features such as component uniformity and desired properties. As used herein, the terms "pharmaceutical", "drug", "drug" and "active ingredient" may be used interchangeably to mean a substance or composition useful for the prevention or treatment of a disease. .. These terms may include pharmaceuticals, dietary supplements, cosmetic agents, biological agents, bioactive substances, and the like. The term "film" is understood to include delivery systems of any thickness, such as films and film strips, sheets, discs, wafers, in any shape, such as rectangles, squares, or other desired shapes. The film may be in the form of a continuous roll of film or may be formed to a desired length and width. The films described herein may be of any desired thickness and size suitable for the intended use. For example, the film of the present invention may be formed so that it can be placed in the oral cavity of the user. Other films may be formed for application to the user's skin, i.e. topical use. For example, some films may have a relatively thin thickness of about 0.1 to about 10 mils, while others may have a somewhat thicker thickness of about 10 to about 30 mils. For some films, especially those intended for topical use, the thickness may be thicker, i.e. thicker than about 30 mils. In addition, the term "film" includes single-layer and multi-layer compositions, such as laminated films, coatings on films, and the like. The composition in its dry film form maintains a uniform dispersion of components by processing the film. The film may include a pouch or region of drug between the two films.
As used herein, the term "patch" is intended to include a multi-layer film product, where the first layer (or "backing layer") is the second layer (or "active ingredient"). A film product having a slower dissolution rate than the "layer"). The patches described herein generally include first and second layers that are bonded or laminated to each other so that at least a portion of the surface of the first layer is visible outside the second layer. The second layer has a shorter length and / or width than the first layer (including, but not limited to, the structure shown in FIG. 3B and the structure described in more detail herein). The films formed in the present invention may be suitable for administration to at least one area of the user's body, such as a mucosal area, or an area within the user's body, such as a visceral surface. In some embodiments of the invention, the film is intended for oral administration. In other embodiments, the film is intended for topical administration. As used herein, the term "topical agent" is meant to include an active ingredient applied to a particular surface area. For example, in some embodiments, the topical agent is applied to an area of the skin. In other embodiments, the topical agent may also be applied to mucosal areas of the body such as the oral cavity (eg, oral cavity, sublingual, tongue), vagina, eye and anus within the body. In yet other embodiments, the topical agent is applied to the user's internal organs or other body surface, eg, during surgery, after the surgery is complete, the active ingredient is removed or left in the body. May be good. In other embodiments, the topical agent is applied to a hard surface, such as a particular surface in need of treatment. In another aspect, the film of the invention is ingestible in the body, placed in the user's mouth, and intended to be swallowed when the film decomposes.
The agent may be dispersed throughout the film or may be deposited on one or more surfaces of the film. In either case, it is desirable that the amount of drug per unit area is substantially uniform over the entire film. "Unit area" is intended to include the appropriate unit area, eg, the area of one standard dose unit. It is desirable that the film of the present invention contains components uniformly distributed over the entire volume of a predetermined film. Such uniformity is substantially uniform per unit volume of film, whether the agent is in the matrix of the film or coated, laminated, or stabilized on one or more surfaces thereof. Includes quantity. When such a film is cut into individual units, the amount of drug in that unit can be known with considerable accuracy. It will be appreciated by those skilled in the art that in the films formed herein, the resulting film need not be exactly 100% uniform. It is understood that all that is required is that the film is "substantially uniform", i.e., a small amount of non-uniformity is acceptable. Substantially uniform means, for example, a film in which one region and another region of the film are about 90% uniform in content, or one region and another region of the film are about 95% uniform in content. A film, and most preferably a film in which one region and another region of the film are about 99% uniform in content.
It is desirable that any individual film product formed by the present invention (ie, a product having substantially similar mass and volume) has a content that is substantially uniform to each other. That is, the individual film products formed by the present invention (including individual pharmaceuticals of approximately the same size) should have approximately the same content as each other's film products. Of course, it is understood that slight deviations occur during the manufacturing process, but desirablely, the content of the individual film products should be at least 90% uniform with each other. In other words, "substantially uniform" can mean that the individual film products should vary by about 10% or less from each other. In some embodiments, "substantially uniform" can mean that the individual film products should vary by about 5% or less from each other. Drug uniformity across the film is important in administering to the user an accurate and effective drug dose. Different methods for forming uniform films, as well as different polymers, additives, and filters can be used, eg, US Pat. Nos. 7,425,292, 7,357,891, and which are incorporated herein by reference. , 7,666,337, including the methods and materials described. Any number of active ingredients or pharmaceuticals may be included in the films discussed herein. The active ingredient may be placed in any layer of the film product formed herein, or placed on one or more surfaces of the film product. it can.
Examples of useful drugs are ace inhibitors, anti-angina drugs, anti-arrhythmic drugs, anti-asthma drugs, anti-cholesterol drugs, analgesics, anesthetics, anti-convulsants, antidepressants, anti-diabetic drugs, anti-diarrheal drugs, Antitussives, antihistamines, antihypertensives, anti-inflammatory drugs, antihypertensive blood drugs, anti-manic drugs, anti-vomiting drugs, anti-stroke drugs, anti-thyroid drugs, anti-cancer drugs, anti-virus drugs, acne drugs, alkaloids, Amino acid preparations, antitussives, antihypertensive drugs, antiviral drugs, anabolic agents, systemic and non-systemic anti-infective drugs, anti-neoplastic drugs, anti-Parkinson's disease drugs, anti-rheumatic drugs, appetite enhancers, biological responses Modifiers, blood regulators, bone metabolism regulators, cardiovascular drugs, central nervous system stimulants, cholinesterase inhibitors, contraceptives, expectorants, nutritional supplements, dopamine receptor agonists, endometriosis drugs, enzymes , Erectile disorder drug, pregnancy drug, gastrointestinal drug, homeopathy therapy drug, hormone, antihypertensive and low calcium blood control drug, immunomodulator, immunosuppressant, sickness drug, vehicle sickness drug, muscle relaxant, obesity Therapeutic agents, osteoporosis preparations, uterine contractile agents, parasympathetic blockers, parasympathetic agents, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, expectorants, sympathetic blockers, tremors, urinary tract agents , Vasodilators, laxatives, antioxidants, ion exchange resins, antihypertensives, appetite suppressants, expectorants, anti-anxiety drugs, anti-ulcer drugs, anti-inflammatory drugs, coronary artery dilators, cerebral dilators, peripheral vasodilators , Antipsychotics, stimulants, antihypertensives, vasodilators, migraine treatments, antibiotics, tranquilizers, antipsychotics, antitumor agents, anticoagulants, antithrombotic agents, sleeping pills, antivomiting agents, Antitussives, antispasmodics, neuromuscular drugs, antihypertensive and hypoglycemic drugs, thyroid and antithyroid preparations, diuretics, antispasmodics, uterine relaxants, antitussives, erythropoiesis, antiasthma, antitussives, mucolytics Drugs, DNA and gene regulators, and combinations thereof.
Examples of the active ingredient for dosing considered for use in the present invention include antacids, H<sub>2</sub>-Antagonists and analgesics are included. For example, antacids can be prepared using raw materials in combination with calcium carbonate alone or magnesium hydroxide and / or aluminum hydroxide. In addition, the antacid is H<sub>2</sub>-Can be used in combination with antagonists.
Painkillers include achens and derivatives, such as oxycodon (commercially available as Oxycontin®), ibuprofen (Motrin®, Advil®, Motrin Children's®, Motrin IB®). , Advil Children's®, Motrin Infants'®, Motrin Junior®, Ibu-2®, Proprinal®, Ibu-200®, Midor Cramp Formula® Trademarks), Bufen®, Motrin Migraine Pain®, Addaprin® and Haltran® commercially available), Aspirin (Empirin®, Ecotrin®, Genuine Bayer® Trademarks), and commercially available as Halfprin®), acetaminophen (Silapap Infant's®, Silapap Children's®, Tylenol®, Tylenol Children's®, Tylenol Extra Strength®, Tylenol Infants' Original®, Tylenol Infants'®, Tylenol Arthritis®, T-Painol®, Q-Pap®, Cetafen®, Dorono®, Tycolene®, APAP® and Aminofen® ), And combinations thereof, which may contain caffeine. Other analgesics may be used in the present invention, such as meperidine hydrochloride (commercially available as Demerol®), capsaicin (commercially available as Qutenza®), morphine sulfate and naltrexone hydrochloride (Embeda®). ), Hydromorphone hydrochloride (commercially available as Dilaudid®), propoxyphennaphthylate and acetaminophen (commercially available as Darvocet-N®), fentanyl (Duragesic®, Onsolis®) ), And fentora® (commercially available as Fentora®), sodium hyaluronate (commercially available as Euflexxa®), adalimumab (commercially available as Humira®), sumatriptan succinate (commercially available as Imitrex®), Fentanyl ion introduction (commercially available as Ionsys®), orphenadrincitrate (commercially available as Norgesic®), magnesium salicylate tetrahydrate (commercially available as Novasal®), oxymorphone hydrochloride (Opana ER) (Commercially available as (registered trademark)), Metcarbamole (commercially available as Robaxin®), Carisoprodol (commercially available as Soma®), Tramadol hydrochloride (Ultracet® and Ultram® Commercially available as), Morphine Sulfate (MS)
The invention may further include agents such as NSAIDs, etodrac (commercially available as Lodine®), ketrolactromethamine (commercially available as Acular® or Acuvail®), naproxen sodium (Anaprox). (Registered trademark), Naprosyn® (commercially available as), Flurbiprofen (commercially available as Ansaid®), diclofenac sodium / misoprostor (commercially available as Arthrotec®), Celebrex (registered trademark) ), Slindak (commercially available as Clinoril®), Oxaprosin (commercially available as Daypro®), Pyroxycam (commercially available as Feldene®), Indomethacin (commercially available as Indocin®), Meloxycam (Commercially available as Mobic®), mephenamic acid (commercially available as Pontel®), sodium tolectin (commercially available as Tolectin®), magnesium choline trisalicylate (commercially available as Trilisate®), diclofenac Examples include sodium (commercially available as Voltaren®), diclofenac potassium (commercially available as Cambia® or Zipsor®), and misoprostor (commercially available as Cytotec®). Opiate agonists and antagonists such as buprenorphine and naloxone are examples of additional drugs used in the present invention.
Other preferred drugs for other preferred active ingredients used in the present invention include antidiarrheal agents, such as loperamide (Imodium AD®, Imotil®, Kaodene®, Imperim). (Registered Trademark), Diamode®, QC Anti-Diarrheal®, Health Care America Anti-Diarrheal®, Leader AD®, and Imogen®, nitazoxanide (Alinia®) and diphenoxylate hydrochloride / atropine sulfate (commercially available as Lomotil®), antihistamines, antitussives, Examples include decongestants, vitamins, and halitosis refreshers. Used alone or for colds, pain, fever, cough, congestion, nasal discharge, and allergies (eg acetaminophen, ibuprofen, chlorpheniramine maleate, dextromethorphan, dextromethorphan hydrochloride, phenilefurin hydrochloride, Pseudoephedrine hydrochloride, diphenhydramine and combinations thereof can be combined with conventional drugs (eg, dextromethorphan hydrobromide and phenilefurin hydrochloride (available as Triaminic®)) in the film compositions of the present invention. It may be contained in.
Other active ingredients useful in the present invention include, but are not limited to, alcohol dependence treatments such as azelastine calcium (commercially available as Campral®); allergy therapeutic agents such as promethazine hydrochloride (Phenergan®). Commercially available), bepotastine besilate (commercially available as Bepreve®), hydrocodonpolistylex / chlorpheniramine polystylex (commercially available as Tussionex®), cetirizine hydrochloride (commercially available as Zyrtec®) , Cetirizine Hydrochloride / Psoid Ephedrine Hydrochloride (commercially available as Zyrtec-D®), Promethazine Hydrochloride / Codein Phosphate (commercially available as Phenergan® and Codein), Pemirolast (commercially available as Alamast®), Fe Xofenazine hydrochloride (commercially available as Allegra®), cetirizine hydrochloride (commercially available as Antivert®), azelastine hydrochloride (commercially available as Astelin®), nizatidine (commercially available as Axid®) , Desloratadine (commercially available as Clarinex®), Sodium cromoglycate (commercially available as Crolom®), Epinastine hydrochloride (commercially available as Elestat®), Azelastine hydrochloride (commercially available as Optivar®) ), Sodium prednisolone phosphate (commercially available as Orapred ODT®), olopatadine hydrochloride (commercially available as Patanol®), ketotiphenfumarate (commercially available as Zaditor®), and sodium montelcasto (Singulair®). Commercially available as a trademark);And antihistamines such as diphenhydramine hydrochloride (commercially available as Benadryl®), loratadine (commercially available as Claritin®), astemizole (commercially available as Hismanal®), nabumetone (commercially available as Relafen®), Examples include diphenhydramine hydrochloride (commercially available as TheraFlu®) and clemastine (commercially available as Tavist®).
The films of the present invention are further treated with Alzheimer's agents such as tacrine hydrochloride (commercially available as Cognex®), galantamine (commercially available as Razadyne®), donepezil hydrochloride (commercially available as Aricept®), rivastigmine. Nitroglycerin (commercially available as Exelon®), caprylidene (commercially available as Axona®), and Memantin (commercially available as Namenda®); anemia treatments such as cyanocobalamine (Nascobal®). (Commercially available as) and Fermoxidol (commercially available as Ferrahem®); anesthetics such as antipyrine and benzokine (commercially available as Auralgan®, Aurodex® and Auroto®); treatment of angina Agents such as amlogipine vesylate (commercially available as Norvasc®), nitroglycerin (Nitro-Bid®, Nitro-Dur®, Nitrolingual®, Nitrostat®, Transderm-Nitro (Marketed as Trademark), Isosorbide mononitrate (marketed as Imdur®), and Isosorbidodinitrate (commercially available as Isordil®); antitussives such as guaifenecin; anti-Alzheimer agents such as nisergorin; and Ca<sup>H</sup>-An antagonists such as nifedipine (commercially available as Procardia® and Adalat®) may be included.
As useful active ingredients in the present invention, anti-asthma drugs such as albuterol sulfate (commercially available as Proventil®), ipratropium bromide (commercially available as Atrovent®), salmeterol xinafoate (Serevent®). ), Zafillucast (commercially available as Accorate®), Flunisolide (commercially available as AeroBid®), Metaproterenol salbutamol (commercially available as Alupent®), Albuterol inhalant (Ventolin®) Commercially available as), terbutalin salbutamol (commercially available as Brethine®), formoterol (commercially available as Foradil®), sodium chromoglycate (commercially available as Intal®), levalvterol hydrochloride (Xopenex®). Commercially available as Trademark), Zyflo (commercially available as Zyflo®), fluticazone propionate / salmeterol (commercially available as Advair®), albuterol sulfate / triamsinolone acetonide (commercially available as Azmacort®), dimethylxanthin (Commercially available as Theophylline®) and Beclomethasone (commercially available as Beclovent®, Beconase®, Qvar®, Vancenase®, Vanceril®); , For example, C1 esterase inhibitor (human) (commercially available as Berinert®), and salbutamol (commercially available as Kalbitor®);And antibacterial agents such as trimetoprim / sulfafurazole (commercially available as Bactrim®), mupirocin (commercially available as Bactroban®), metronidazole (commercially available as Flagyl®), acetylsulfisoxazole. (Commercially available as Gantrisin®), bismas subsalicylate and metronidazole / tetracycline hydrochloride (commercially available as Helidac Therapy®), nitrofurantoin (commercially available as Macrodantin®), norofloxacin (registered) Examples include commercially available), erythromycin ethylsuccinate / acetylsulfisoxazole (commercially available as Pediazole®), and levofloxacin (commercially available as Levofloxacin®).
The present invention further relates to amoxicillin (commercially available as Amoxicillin®), ampicillin (commercially available as Omnipen®, Polycillin® and Principen®), amoxicillin / potassium clavrate (Augmentin®). ), Moxifloxacin hydrochloride (commercially available as Avelox®), Besifloxacin (commercially available as Besivance®), Clarislomycin (commercially available as Biaxin®), Cedax (registered) Commercially available as (trademark), cefproximaxetyl (commercially available as Ceftin®), cefprozil (commercially available as Cefzil®), ciprofloxacin hydrochloride (commercially available as Ciloxan® and Cipro®) Commercially available), Cleocin T (commercially available as a registered trademark), doxycycline hydrochloride (commercially available as Doryx®), dythromycin (commercially available as Dynabac®), erythromycin (EES®, E-Mycin®) , Eryc®, Ery-Tab®, Erythrocin®, and PCE® commercially available), Topical Erythromycin (A / T / S®, Erycette®) , T-Stat® (commercially available as T-Stat®), Gemifloxacin (commercially available as Factive®), Ofloxacin (commercially available as Ocuflox®, Floxin®), Erythromycin (commercially available as Ketek®) Commercially available), ofloxacin hydrochloride (commercially available as Maxaquin®), minocycline hydrochloride (commercially available as Minocin®), phosphomycintromethamine (commercially available as Monurol®), penicillin and potassium (commercially available) VK®, Veetids®, trimethoprim (commercially available as Primsol®), ciprofloxacin hydrochloride (commercially available as Proquin XR®), rifampin, isoniazid and pyrazineamide (commercially available as Proquin XR®) Rifater® (commercially available as), Cefditoren (commercially available as Spectracef®), Cefixime (commercially available as Suprax®), Tetracycline (Achromycin) V (registered trademark) and Sumycin (registered trademark), tobramycin (commercially available as Tobrex (registered trademark)), rifaximin (commercially available as Xifaxan (registered trademark)), azithromycin (commercially available as Zithromax (registered trademark)), azithromycin suspension Turbid liquid (commercially available as Zmax®), linezolide (commercially available as Zyvox®), benzoyl peroxide and clindamycin (commercially available as BensaClin®), erythromycin and benzoyl peroxide (registered trademark) ), Dexametazone (commercially available as Ozurdex®), cyprofloxacin and dexamethasone (commercially available as Ciprodex®), polymyxin B sulfate / neomycin sulfate / hydrocortisone (commercially available as Cortisporin®), Cortisporin-TC 1 such as Otic®, cephalexin hydrochloride (commercially available as Keflex®), cefdinir (commercially available as Omnicef®), and gatifloxacin (commercially available as Zymar®). The above antibiotics may be included.
Other useful active ingredients include cyclophosphamide (commercially available as Cytoxan®), methotrexate (commercially available as Rheumatrex® and Trexal®), and tamoxyfencitrate (commercially available as Nolvadex®). ), Bebasizumab (commercially available as Avastin®), Eberolimus (commercially available as Afinitor®), Pazopanib (commercially available as Votrient®), and Anastrosol (commercially available as Arimidex®); Leukemia Therapeutic agents such as ofatumumab (commercially available as Arzerra®); antithrombotic agents such as antithrombin recombinant lyophilized powder (commercially available as Atryn®), prasugrel (commercially available as Efient®); anticoagulants , For example, aspirin and sustained-release dipyridamole (commercially available as Aggrenox®), sodium warfarin (commercially available as Coumadin®), dipyridamole (commercially available as Persantine®), dartepalin (commercially available as Fragmin®). , Danaparoid (commercially available as Orgaran®), Enoxapalin (commercially available as Lovenox®), Heparin (commercially available as Hep-Lock, Hep-Pak, Hep-Pak CVC, Heparin Lock Flush), Chinzaparin (Innohep (registered)) Commercially available as (trademark), and clopidogrel bisulfate (commercially available as Plavix®); antiemetics such as granisetron hydrochloride (commercially available as Kytril®) and Naviron (commercially available as Cesamet®), Trimet Benzamide hydrochloride (commercially available as Tigan®) and Ondancetron hydrochloride (commercially available as Zofran®);Antifungal agents such as ketoconazole (commercially available as Nizoral®), posaconazole (commercially available as Noxafil®), cyclopyroxis (commercially available as Penlac®), glyceofrubin (commercially available as Gris-PEG®). ), Oxistat (commercially available as Oxistat®), Fluconazole (commercially available as Diflucan®), Sertaconazolenitrate (commercially available as Ertaczo®), Terbinafine hydrochloride (Lamisil®) Commercially available as (trademark), Cyclopyrox (commercially available as Loprox®), Nystatin / triamsinolone acetonide (commercially available as Mycolog-II®), Econazolenitrate (commercially available as Spectazole®), Itraconazole (commercially available as Spectazole®) Examples include cancer therapeutic agents such as Sporanox® (commercially available as a registered trademark) and terconazole (commercially available as Terazol®).
In addition, as active ingredients, anti-inflammatory agents such as hydroxychloroquine sulfate (commercially available as Plaquenil®), fluticasone propionate (commercially available as Cutivate®), canakinumab (commercially available as Llaris®), amcinonide (Cyclocort). (Commercially available as Registered Trademark), Methylprednisolone (Commercially available as Medrol®), Budesonide (Entocort) EC® (commercially available as EC®), anakinra (commercially available as Kineret®), diflorason diacetate (commercially available as Psorcon®), and etanercept (commercially available as Enbrel®); Anticonvulsants such as phenobarbital / hyostiamine sulfate / atropine sulfate / scopolamine hydrobromide (commercially available as Donnatal®); antiviral treatments such as oseltamivir phosphate (commercially available as Tamiflu®); Parasite drugs, tinidazole (commercially available as Tindamax®), etc .; appetite remedies such as Megace roll acetate (Megace) ES® (trademark), Fentermin hydrochloride (commercially available as Adipex-P®), and diethylpropion hydrochloride (commercially available as Tenuate®); arthritis drug, leflunomide (commercially available as Arava®) Sertrizumab pegol (commercially available as Cimzia®), diclofenac sodium (commercially available as Pennsaid®), golimumab (commercially available as Simponi®), and tosirizumab (commercially available as Actemra®), etc. Bladder control agents such as trospium chloride (commercially available as Sanctura®), desmopressin acetate (commercially available as DDAVP®), tortellodin tartrate (commercially available as Detrol®), oxybutynin chloride (commercially available as) Ditropan® or Gelnique® (commercially available), Darifenacin (commercially available as Enablex®), and Solifenasin Succinate (commercially available as VESIcare®); Commercially available as Methergine®; Plasma urine control agents, such as Lasbricase (commercially available as Elitek®); Iron deficient anemia agents, such as Feramexil (commercially available as Ferrahem®); Lymphoma therapeutic agents, For example, Pralatrexate (commercially available as Folotyn®), Lomidepsin (commercially available as Isodax®); Malaria treatments such as Artemeter / Lumephantrin (commercially available as Coartem®); Treatment of hyponatremia Agents such as tolbaptan (commercially available as Samsca®); von Willebrand's disease treatment (commercially available as Wilate®); antihypertensive agents such as treprostinil (commercially available as Tyvaso®), Tadalafil (Adcirca (registered trademark)) Commercially available as a registered trademark);Cholesterol-lowering drugs such as paricalsitol (commercially available as Altocor®), pitavastatin (commercially available as Livalo®), lovastatin, niacin (commercially available as Advicor®), cholestid® ), Losvastatin calcium (commercially available as Crestor®), Fluvastatin sodium (commercially available as Lescol®), Atorvastatin calcium (commercially available as Lipitor®), Lovastatin (commercially available as Mevacor®) Commercially available), niacin (commercially available as Niaspan®), pravastatin sodium (commercially available as Pravachol®), pavastatin sodium and buffer aspirin (commercially available as Pravigard PAC®), cholestyramine (Questran) (Commercially available as (registered trademark)), simvastatin and niacin (commercially available as Simcor®), atenolol, chlortalidone (commercially available as Tenoretic®), atenolol (commercially available as Tenormin®), fenofibrate (Tricor (commercially available)) Commercially available as registered trademark), fenofibrate (commercially available as Triglide®), ezetimib / limovastatin (commercially available as Vytorin®), cholestyramine (commercially available as WelChol®), bisoprolofumarat (registered as Zebeta) Examples include commercial), ezetimib (commercially available as Zetia®), bisoprolofumarate / hydrochlorothiazide (commercially available as Ziac®), and simvasstatin (commercially available as Zocor®).PAC (commercially available as registered trademark), cholestyramine (commercially available as Questran®), simvastatin and niacin (commercially available as Simcor®), atenolol, chlortalidone (commercially available as Tenoretic®), atenolol (tenormin) Commercially available as (registered trademark), fenofibrate (commercially available as Tricor®), fenofibrate (commercially available as Triglide®), ezetimibe / simvastatin (commercially available as Vytorin®), cholestyramine (commercially available as WelChol®) Commercially available as (trademark), bisoprolofumarate (commercially available as Zebeta®), ezetimibe (commercially available as Zetia®), bisoprolol fumarate / hydrochlorothiazide (commercially available as Ziac®), and simvastatin (Zocor (commercially available)). Commercially available) as a registered trademark).
As active ingredients contained herein, and chronic kidney disease agents such as paricalcitol (commercially available as Zemplar®); contraceptives such as etnogestrel (commercially available as Implanon®), noruetin. Delon acetate, ethinyl estradiol (commercially available as Loestrin 24 FE®), ethinyl estradiol, norelgestromin (commercially available as Ortho Evra®), levonorgestrel (Plan) B®, levonorgestrel and ethynyl estradiol (commercially available as Preven®), levonorgestrel, ethynyl estradiol (commercially available as Seasonique®), and medroxyprogesterone acetate (Depo-Provera) Commercially available as a registered trademark); COPD treatments such as alformoterol tartrate (commercially available as Brovana®) and ipratropium bromide, albuterol sulfate (commercially available as Combivent®); as benzonatate (Tessalon®). Antitussives, including (commercially available), guayphenesin, codeine phosphate (commercially available as Tussi-Organidin NR®), and acetaminophen, codeine phosphate (commercially available as Tylenol with Codeine®); Pioglycazone hydrochloride, metformin hydrochloride (ACTOplus) Met® (commercially available as registered trademark), bromocryptine mesylate (commercially available as Cycloset®), liraglutide (commercially available as Victoza®), saxagliptin (commercially available as Onglyza®), pioglycazone hydrochloride (Actos (commercially available)) Commercially available as (registered trademark)), Glymepyride (commercially available as Amaryl®), rosiglitazone maleate, metformin hydrochloride (commercially available as Avandamet®), rosiglitazone maleate (commercially available as Avandaryl®), Losiglitazone Maleart (commercially available as Avandia®), Exenatide (commercially available as Byetta®), Chlorpropamide (commercially available as Diabinese®), Pioglycazone hydrochloride, Glymepyride (as Duetact®) Commercially available), Metformin hydrochloride (commercially available as Glucophage®), Glypidide (commercially available as Glucotrol®), Glybrid, Metformin (commercially available as Glucovance®), Metformin hydrochloride (commercially available as Glumetza®) Commercially available), sitagliptin (commercially available as Januvia®), detemil (commercially available as Levemir®), gripidide, metformin hydrochloride (commercially available as Metaglip®), glybrid (commercially available as Micronase®) , Repaglinide (commercially available as Prandin®), Acarbose (commercially available as Precose®), Nateglunide (commercially available as Starlix®), Plum Lynchdo Setate (commercially available as Symlin®), and Examples include trazamide (commercially available as Tolinase®).
Other useful agents of the invention include digestive agents such as sucralfate (commercially available as Azulfidine®), rabeprazole sodium (commercially available as AcipHex®), rubiprostone (commercially available as Amitiza®), dicyclomine hydrochloride. Salt (commercially available as Bentyl®), sucralfate (commercially available as Carafate®), lacturose (commercially available as Chronulac®), docusate (commercially available as Colace®), balsalazid disodium (Colazal (commercially available)) Commercially available as (registered trademark)), Rosaltan potassium (commercially available as Cozaar®), Orsalazine sodium (commercially available as Dipentum®), chlordiazepoxide hydrochloride, cridinium bromide (commercially available as Librax®), Eso Meprazole magnesium (commercially available as Nexium®), famotidine (commercially available as Pepcid®), lansoprazole (commercially available as Prevacid®), lansoprazole and naproxene (Prevacid) NapraPAC®, Amoxicillin / Clarislomycin / Lansoprazole (Prevpac®), Omeprazole (Prilosec®), Pantoprazole Sodium (Protonix®), Metoclopramid hydrochloride (commercially available as Reglan® or Metozolv®), simetidine (commercially available as Tagamet®), ranitidine hydrochloride (commercially available as Zantac®), and omeprazole, sodium bicarbonate ( Zegerid®; Commercially available as (registered trademark), chlorothiazide (commercially available as Diuril®), furosemide (commercially available as Lasix®), metrazone (commercially available as Zaroxolyn®), and hydrochlorothiazide, triamterene (registered). Commercially available) as a trademark).
As a useful agent herein, and as a therapeutic agent for emphysema, such as thiotropium bromide (commercially available as Spiriva®); as a therapeutic agent for fibromyalgia, eg, Milnashiplan hydrochloride (Savella®). Commercially available); Gout remedies such as Colchtin (commercially available as Colcrys®) and febuxostat (commercially available as Uroric®); enema remedies, aminosalicylic acid (Mesalamine® and Rowasa®) Etc .; epithelial agents such as valproic acid (commercially available as Depakene®), ferbamate (commercially available as Felbatol®), lamotridin (commercially available as Lamictal®), primidone (commercially available as Mysoline®). Commercially available as), oxcarbazepine (commercially available as Trileptal®), zonisamide (commercially available as Zonegran®), levetiracetam (commercially available as Keppra®), and sodium phenytoin (commercially available as Dilantin®). (Commercially available).
As a therapeutic agent for erectile dysfunction useful herein, it promotes blood flow to the penis, such as, but not limited to, increasing parasympathetic (cholinergic) activity and decreasing sympathetic (adrenalinergic) activity. , And agents for effective autonomic activity. Drugs useful for treating erectile disorders include, for example, alprostadil (commercially available as Caverject®), tadalafil (commercially available as Cialis®), vardenafil (commercially available as Levitra®), apomorphine (Uprima (commercially available)). Drugs available as commercially available), yohinbin hydrochloride (commercially available as Aphrodyne®, Yocon®), and sildenafil citrate (commercially available as Viagra®).
In addition, as agents useful herein, ophthalmic agents and therapeutic agents such as dipibefloxacin hydrochloride (commercially available as Propine®), valganciclovir (commercially available as Valcyte®), ganciclovir ophthalmic gel (Zirgan) Commercially available as Registered Trademark); Bepotastine Besilate (commercially available as Bepreve®), Besifloxacin (commercially available as Besivance®), Bromphenac (commercially available as Xibrom®), Fluorometholone (FML®) Commercially available as (trademark), pilocarpine hydrochloride (commercially available as Pilocar®), cyclosporine (commercially available as Restasis®), brimonidine tartrate (Alphagan) P® (commercially available as registered trademark), Dorzolamide hydrochloride / timolol maleate (commercially available as Cosopt®), Bimatoprost (commercially available as Lumigan®), Timolol maleate (available as Timoptic®) , Travoprost (commercially available as Travatan®), Latanoprost (commercially available as Xalatan®), Ecothiofate iodide (commercially available as Phospholine Iodide®), and Ranibizumab (commercially available as Lucentis®). ); Fluid controllers such as acetazolamide (marketed as Diamox®); bile stone treatment, ursodiol (marketed as Actigall®), etc .; gingilitis treatment, chlorhexidine gluconate (marketed as Peridex®) ) Etc.; headache drug, butalbital / codeinphosphate / aspirin / caffeine (Fiornal® with) Commercially available as Codeine), Naratriptan hydrochloride (commercially available as Amerge®), Almotriptan (commercially available as Axert®), Ergotamine tartrate / caffeine (commercially available as Cafergot®), Butalbital / Acet Aminophen / caffeine (commercially available as Fioricet®), butarbital / aspirin / caffeine (commercially available as Fiorinal®), flovatriptan succinate (commercially available as Frova®), rizatriptan benzoate (commercially available as Frova®) Maxalt® (commercially available as registered trademark), isometeptenmucate / dichloralphenazone / acetaminophen (commercially available as Midrin®), dihydroergotamine mesylate (commercially available as Migranal®), etriptan hydrogen bromide Latex (commercially available as Relpax®) and zormitriptan (commercially available as Zomig®); influenza drugs such as hemophilus b vaccine; tetanus toxoid conjugate (commercially available as Hiberix®); And cardiac remedies such as quinidine sulfate, isosorbidodinitrate / hydrarazine hydrochloride (commercially available as BiDil®), digoxin (commercially available as Lanoxin®), flecainidoacetate (commercially available as Tambocor®), Triptans (commercially available as Mexitil®), disopyramide phosphate (commercially available as Norpace®), procaineamide hydrochloride (commercially available as Procanbid®), and propaphenone (commercially available as Rythmol®). ).
Other useful agents include hepatitis treatments such as entecavir (commercially available as Baraclude®), hepatitis B immunoglobulin (HepaGam). B® (commercially available as Ribavirin®), and copegus / rebetol / ribasphere / virona / virazole (commercially available as Ribavirin®); herpes remedies such as famciclovir. Hydrochloride (commercially available as Valtrex®), pencyclovir (commercially available as Denavir®), acyclovir (commercially available as Zovirax®), and famciclovir (commercially available as Famvir®);Antihypertensive drugs such as enalaprilato (available as Vasotec®), captopril (available as Capoten®) and lisinopril (available as Zestril®), bellapamil hydrochloride (Calan®) (Available as), Ramipril (commercially available as Altace®), Ormesartan medoxomil (commercially available as Benicar®), Amlogipin / Atrubastatin (commercially available as Caduet®), Nicaldipine hydrochloride (Cardene®) (Commercially available as), diltiazem hydrochloride (commercially available as Cardizem®), quinapril hydrochloride (commercially available as Accupril®), quinapril hydrochloride / hydrochlorothiazide (commercially available as Accuretic®), perindopril erbumin (Aceon) (Commercially available as (registered trademark)), candesartan cilexetil (commercially available as Atacand®), candesartan cilexetil / hydrochlorothiazide (Atacand)HCT® (commercially available as HCT®), irbesartan / hydrochlorothiazide (commercially available as Valide®), irbesartan (commercially available as Avapro®), amlogipine vesylate / olmesartan medoxomil (commercially available as Azor®), levobunolol Hydrochloride (commercially available as Betagan®), Betaxolol hydrochloride (commercially available as Betoptic®), Neviborol (commercially available as Bystolic®), Captopril / Hydrochlorothiazide (commercially available as Capozide®), Doxazosin Mecilat (commercially available as Cardura®), Chronidine hydrochloride (commercially available as Catapres®), Carvegirol (commercially available as Coreg®), Nadolol (commercially available as Corgard®), Nadolol / Bend Hydrochlorothiazide (commercially available as Corzide®), balsartan (commercially available as Diovan®), irbesartan (commercially available as DynaCirc®), guanabends acetate (commercially available as Wytensin®), guanfacin hydrochloride Salt (commercially available as Tenex® or Intuniv®), rosartan potassium / hydrochlorothiazide (commercially available as Hyzaar®), propranolol hydrochloride (commercially available as Indera®), propranolol hydrochloride / hydrochlorothiazide (commercially available as Indera®) Inderide® (commercially available as Inderide®), Eprelenon (commercially available as Inspra®), Ambricentan (commercially available as Letairis®), Enarapril Maleato / Ferrodipine (commercially available as Lexxel®), Metoprorol tartrate (Commercially available as Lopressor®), Benazepril Hydrochloride (Commercially available as Lotensin®), Benazepril Hydrochloride / Hydrochlorothiazide (Lotensin)HCT® (commercially available as HCT®), Amlogipine / Benazepril Hydrochloride (commercially available as Lotrel®), Indapamide (commercially available as Lozol®), Trandrapril (commercially available as Mavik®), Termisartane ( Micardis® (commercially available as), thermisartane / hydrochlorothiazide (commercially available as Micardis HCT®), prazosin hydrochloride (commercially available as Minipress®), amylolide, hydrochlorothiazide (commercially available as Moduretic®), fo. Synopril sodium (commercially available as ZZXT Monopril®), phosinopril sodium / hydrochlorothiazide (commercially available as Monopril-HCT®), pindrol (commercially available as Visken®), ferrodipin (Plendil®). (Commercially available as), sildenafilcitratate (commercially available as Revatio®), nisoldipine (commercially available as Sular®), trandrapril / verapamil hydrochloride (commercially available as Tarka®), alkturna (registered) Commercially available as (trademark)), Eprosartan mesylate (commercially available as Teveten®), Eprosartan mesylate / hydrochlorothiazide (commercially available as Teveten HCT®), Moexipril hydrochloride / hydrochlorothiazide (commercially available as Uniretic®). ), Moexipril hydrochloride (commercially available as Univasc®), enalapril maleate / hydrochlorothiazide (commercially available as Vaseretic®), and ricinopril / hydrochlorothiazide (commercially available as Zestoretic®).Commercially available as HCT®, moexipril hydrochloride / hydrochlorothiazide (commercially available as Uniretic®), moexipril hydrochloride (commercially available as Univasc®), enalapril maleate / hydrochlorothiazide (commercially available as Vaseretic®) ), And lisinopril / hydrochlorothiazide (commercially available as Zestoretic®).
The present invention relates to agents useful in pharmaceuticals for the treatment of HIV / AIDS, such as amprenavir (commercially available as Agenerase®), tipranavir (commercially available as Aptivus®), efavirenz / emtricitabine / tenofobil (commercially available as Aptivus®). Atripla® (commercially available as registered trademark), lamivudine / zidobudin (commercially available as Combivir®), indinavir sulfate (commercially available as Crixivan®), lamivudine (commercially available as Epivir®), saquinavir (commercially available as Fortovase®) Commercially available as trademark), Saquinavir (commercially available as Hivid®), Lopinavir / litnavir (commercially available as Kaletra®), Fosaprenavir calcium (commercially available as Lexiva®), Lithnavir (registered as Norvir®) Commercially available as Trademark), Zidobudin (Commercially available as Retrovir®), Atazanavir Sulfate (Commercially available as Reyataz®), Efavirenz (Commercially available as Sustiva®), Abacavir / Lamivudine / Zidobudine (Trizivir®) ), Didanocin (commercially available as Videx®), Nerphinavir mesylate (commercially available as Viracept®), Nevirapine (commercially available as Viramune®), Tenofobirgisoproxil fumarate (Viread (commercially available)) Commercially available as registered trademark), stubzine (commercially available as Zerit®), and abacavir sulfate (commercially available as Ziagen®); homocysteine remover, betaine anhydride (commercially available as Cystadane®), etc .; pharmaceuticals , For example, insulin (commercially available as Apidra®, Humalog®, Humulin®, Iletin®, and Novolin®);And HPV therapeutics such as human papillomavirus vaccine (commercially available as Gardasil®) or divalent human papillomavirus (commercially available as Cervarix®); immunosuppressants such as cyclosporine (Gengraf®, Neoral®). ), Sandimmune®, and Apo-Cyclosporine® (commercially available).
As useful agents in the present invention, progestin inhibitors such as bromocryptine mesylate (commercially available as Parlodel®); pharmaceuticals to assist stress testing such as ligadenoson (commercially available as Lexiscan®); baldness. Finasteride (commercially available as Propecia® and Proscar®), etc .; Pancreatitis therapeutic agents, such as gemfibrodil (commercially available as Lopid®); Hormonal agents, such as noretindrone acetate / ethynyl estradiol ( femHRT (commercially available as a registered trademark), goselelin acetylate (commercially available as Zoladex®), progesterone gel (commercially available as Prochieve®), progesterone (commercially available as Prometrium®), salacalcin (Miacalcin (commercially available as a registered trademark)) Commercially available as a registered trademark), Calcitriol (commercially available as a Rocaltrol®), Synthroid (commercially available as Levothroid®, Levoxyl®, Unithroid®), Testopel (Registered Trademark), Androderm (Registered Trademarks), Testoderm®, and AndroGel® (commercially available);Estradiol / noretindrone acetate (marketed as Activella®), drospyrenone / estradiol (commercially available as Angeliq®), estradiol / levonolgestrel (commercially available as Climara Pro®) , Estradiol / noretindron acetate (commercially available as CombiPatch®), estradiol (commercially available as Estrasorb®, Vagifem® and EstroGel®), esterified estrogen and methyltestosterone (Estratest (registered trademark)) Commercially available as (registered trademark)), estrogen (commercially available as Alora®, Climara®, Esclim®, Estraderm®, Vivelle®, Vivelle-Dot®), Estropipet (commercially available as Ogen®), conjugate estrogen (commercially available as Premarin®) and medroxyprogesterone acetate (commercially available as Provera®); menstrual drug, Lupron Commercially available as Depot), tranexamic acid (commercially available as Lysteda®), and noruetindron acetate (commercially available as Aygestin®); and muscle relaxants such as cyclobenzaprine hydrochloride (Flexeril®). (Commercially available), tizanidine (commercially available as Zanaflex®), and hyostiamine sulfate (commercially available as Levsin®).And muscle relaxants such as cyclobenzaprine hydrochloride (commercially available as Flexeril®), tizanidine (commercially available as Zanaflex®), and hyoscyamine sulfate (commercially available as Levsin®).And muscle relaxants such as cyclobenzaprine hydrochloride (commercially available as Flexeril®), tizanidine (commercially available as Zanaflex®), and hyoscyamine sulfate (commercially available as Levsin®).
As useful agents herein, and therapeutic agents for osteoporosis, such as ibrandronate sodium (commercially available as Boniva®), resedronate (commercially available as Actonel®), laoxyphene hydrochloride (Evista (commercially available)). Commercially available as Registered Trademarks, Fortical®, and Sodium Alendronate (commercially available as Fosax®); ovulation promoter, clomiphenecitrate (Serophene®, Clomid®, Serophene® Commercially available as a registered trademark), etc .; therapeutic agents for Paget's disease, such as disodium etidronate (commercially available as Didronel®); therapeutic agents for pancreatic enzyme deficiency, such as Pancrease® or Zenpep®. Drugs for the treatment of Parkinson's disease, such as plamipexol dihydrochloride (commercially available as Milapex®), lopinilol hydrochloride (commercially available as Requip®), carbidopa / levodopa (Sinemet). CR® (commercially available as CR®), Calvidopa / Levodopa / Entacapone (commercially available as Stalevo®), Selegiline hydrochloride (commercially available as Zelapar®), Lasagiline (commercially available as Azilect®), Entacapone (commercially available as Azilect®) Commercially available as Comtan®, and selegiline hydrochloride (commercially available as Eldepryl®); therapeutic agents for multiple sclerosis, such as dalfampridin (commercially available as Ampyra®) and interferon beta Ib (Extavia). Commercially available as (registered trademark); Prostatic agents such as flutamide (commercially available as Eulexin®), niltamide (commercially available as Nilandron®), dutasteride (commercially available as Avodart®), tamsrosin hydrochloride (commercially available as Avodart®). Examples include Flomax® (commercially available as Flomax®), terazosin hydrochloride (commercially available as Hytrin®), and alfuzosin hydrochloride (commercially available as UroXatral®).
The films of the invention are further prepared for the treatment of psychosis, such as alprazolam (available as Niravam®, Xanax®), clozopin (available as Clozaril®), haloperidol (Haldol). Available as Registered Trademark), Fluoxetine Hydrochloride (Available as Prozac®), Celtraline Hydrochloride (Available as Zoloft®), Asenapine (Commercially Available as Saphris®), Iloperidol (Fanapt) Commercially available as (registered trademark)), paroxtine hydrochloride hydrochloride) (available as Paxil®), aripiprazole (commercially available as Abilify®), guanfasin (commercially available as Intuniv®), amphetamine and methanephetamine (Adderall® and Desoxyn®) Commercially available as), Chromipramine hydrochloride (commercially available as Anafranil®), Buspiron hydrochloride (commercially available as BuSpar®), Citaloplum hydrogen bromide (commercially available as Celexa®), Duroxetine hydrochloride (commercially available as Cymbalta) Commercially available as (registered trademark), methylphenidate (commercially available as Ritalin, Daytrana®), divalproexsodium (valproic acid) (commercially available as Depakote®), dextroamphetamine sulfate (registered trademark) ), Venlafaxine hydrochloride (commercially available as Effexor®), Selegiline (commercially available as Emsam®), Carbamazepine (commercially available as Equetro®), Lithium carbonate (Eskalith®) (Commercially available as), Fluboxamine Maleato / Dextroamphetamine Hydrochloride (commercially available as Focalin®), Dibrasdon Hydrochloride (commercially available as Geodon®), Ergoroid Mecilate (commercially available as Hydergine®) , Escitaloplum oxalate (commercially available as Lexapro®), chlordiazepoxide (commercially available as Librium®), morindone hydrochloride (commercially available as Moban®), phenelzine sulfate (commercially available as Nardil®) , Thiothixen (commercially available as Navane®), dexprazole hydrochloride (commercially available as Norpramin®), benzodiazepine (eg, available as Oxazepam®), nortriptyline hydrochloride (Pamelor®)Commercially available as standard), tranylicipromin sulfate (commercially available as Parnate®), protriptyline, mirtazapine (commercially available as Remeron®), risperdal (commercially available as Risperdal®), quetiapin fumarate (Commercially available as Seroquel®), doxepin hydrochloride (commercially available as Sinequan®), atomoxetine hydrochloride (commercially available as Strattera®), trimipramine maleate (commercially available as Surmontil®) , Oranzapine / fluoxetine hydrochloride (commercially available as Symbyax®), imipramine hydrochloride (commercially available as Tofranil®), protriptyline hydrochloride (commercially available as Vivactil®), bupropion hydrochloride (Wellbutrin (registered trademark)) May include (registered trademark), Wellbutrin SR®, and Wellbutrin XR® (commercially available as Wellbutrin XR®), and oranzapine (commercially available as Zyprexa®).It may contain XR (commercially available as a registered trademark) and olanzapine (commercially available as a Zyprexa®).It may contain XR (commercially available as a registered trademark) and olanzapine (commercially available as a Zyprexa®).
As useful agents herein, uric acid reducing therapeutic agents such as allopurinol (commercially available as Zyloprim®); seizure therapeutic agents such as gabapentin (commercially available as Neurontin®), etotoin (Peganone®). ), Vigabatrin (commercially available as Sabril®), and Topiramate (commercially available as Topamax®); therapeutic agents for herpes zoster, such as live herpes zoster vaccine (commercially available as Zostavax®);Skin care agents such as calcipotriene (commercially available as Dovonex®), ustecinumab (commercially available as Stelara®), teravancin (commercially available as Vibativ®), isotretinoin (commercially available as Accutane®) , Hydrocortisone / Isotretinoin (commercially available as Alcortin®), Sulfacetamide sodium / sulfur (commercially available as Avar®), Azeline acid (commercially available as Azelex®, Finacea®), Benzoyl peroxide (commercially available as Desquam-E®), adapalene (commercially available as Differin®), fluorouracil (commercially available as Efudex®), pimechlorimus (commercially available as Elidel®), topical erythromycin (Commercially available as A / T / S®, Erycette®, T-Stat®), Hydrocortisone (commercially available as Cetacort®, Hytone®, Nutracort®) , Metronidazole (commercially available as MetroGel®), Doxycycline (commercially available as Oracea®), Tretinoin (commercially available as Retin-A® and Renova®), Mequinol / Tretinoin (Solage®) ), Acitretinoin (commercially available as Soriatane®), Calcipotriene hydrate / betamethasone dipropionate (commercially available as Taclonex®), Tazarotene (commercially available as Tazorac®), Fluosinone (commercially available as Tazorac®) Vanos® (commercially available), Desonide (commercially available as Verdeso®), myconazole nitrate / zinc oxide (commercially available as Vusion®), ketoconazole (commercially available as Xolegel®), and efarizumab (commercially available as Xolegel®). Raptiva® (commercially available).Honate (commercially available as Taclonex®), Tazarotene (commercially available as Tazorac®), Fluocinonide (commercially available as Vanos®), Desonide (commercially available as Verdeso®), myconazolenitrate / zinc oxide (Commercially available as Vusion®), ketoconazole (commercially available as Xolegel®), and efarizumab (commercially available as Raptiva®).Honate (commercially available as Taclonex®), Tazarotene (commercially available as Tazorac®), Fluocinonide (commercially available as Vanos®), Desonide (commercially available as Verdeso®), myconazolenitrate / zinc oxide (Commercially available as Vusion®), ketoconazole (commercially available as Xolegel®), and efarizumab (commercially available as Raptiva®).
Other agents useful herein include therapeutic agents for sleep disorders such as zaleplon (available as Sonata®), eszopiclone (available as Lunesta®), zolpidem tartrate (Ambien®). ), Ambien CR®, Edluar®, Lorazepam (Ativan®), Flulazepam Hydrochloride (Dalmane®), Triazolam (Halcion®), Clorazepate (commercially available as Klonopin®), Barbiturate (eg Phenobalbital®), Modafinil (commercially available as Provigil®), Temazepam (commercially available as Restoril®), Ramelteon (Rozerem®) ), Dipotassium chlorazepam (commercially available as Tranxene®), Diazepam (commercially available as Valium®), Quazepam (commercially available as Doral®), and Estazolam (commercially available as ProSom®). Over-the-counter); Antihypertensive agents such as valeniclin (commercially available as Chantix®), nicotine such as Nicotrol®, and bupropion hydrochloride (commercially available as Zyban®);And steroids such as alcromethasone dipropionate (commercially available as Aclovate®), betamethasone dipropionate (commercially available as Diprolene®), mometamethasone floart (commercially available as Elocon®), fluticasone. (Commercially available as Flonase®, Flovent®, Flovent Diskus®, Flovent Rotadisk®), fluticasoneide (commercially available as Lidex®), mometamethasone float monohydrate ( Nasonex® (commercially available as Registered Trademark), Desoxymethasone (commercially available as Topicort®), Clotrimazole / Betamethasone dipropionate (commercially available as Lotrisone®), Pred Forte® ), Prednisone®, Budesonide Pulmicort®, Rhinocort Aqua®), Prednisolone sodium phosphate (commercially available as Pediapred®), Desonide (commercially available as Trideshion®), and Examples include halobetazol propionate (commercially available as Ultravate®). The films of the present invention further include agents useful for the treatment of thyroid diseases, such as hormones TC and TD (commercially available as Armor Thyroid®); potassium deficiency therapeutic agents, potassium chloride (commercially available as Micro-K®), etc. Triglyceride regulators, omega-3 fatty acid ethyl ester (commercially available as Omacor®), etc .; urinary remedies such as phenazopyridine hydrochloride (commercially available as Pyridium®) and methenamine, methylene blue / phenylsalicylate / benzoic acid / Atropine sulfate / Hyostiamine (commercially available as Urised®); Pregnant women's vitamins (advanced Natalcare®, Materna®, Natalins®, Prenate Advance®); Drugs for the treatment of obesity, such as orlistat (commercially available as Xenical®) and sibutramine hydrochloride (commercially available as Meridia®) may be included.
Well-known H intended for use in the present invention<sub>2</sub>-Antagonists include cimetidine, ranitidine hydrochloride, famotidine, nizatidien, ebrotidine, mifentidine, roxatidine, pisatidine and aceroxatidine. The anti-acid active ingredient is not limited, but is limited to aluminum hydroxide, dihydroxyaluminum aminoacetate, aminoacetic acid, aluminum phosphate, dihydroxyaluminum sodium carbonate, bicarbonate, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, and the following. Bismus acidite, bismuth hyponitrate, bismus hyposalicylate, calcium carbonate, calcium phosphate, citrate ion (acid or salt), aminoacetic acid, magnesium aluminate sulfate hydrate, magardrate, magnesium aluminate silicate, magnesium carbonate, magnesium glycy Nate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, milk solids, aluminum monobasic or dibasic calcium phosphate, tricalcium phosphate, potassium bicarbonate, sodium tartrate, sodium bicarbonate, magnesium silicate, Examples include tartrate acid and salt.
Pharmaceutical active ingredients used in the present invention include allergens or antigens, such as, but not limited to, plant pollen from grass, trees or ragweed; animal skin and hair with animal scales, cats and other fur. Small flakes shed from; insects such as house dust mites, wasps, and wasps; and drugs such as penicillin. In one particular method for forming a film, a wet film matrix deposits on the surface of the substrate. Any desired substrate can be used, including, for example, mylar, paper, plastic, metal, foil, and combinations thereof. The base material can be laminated if desired. In addition, the substrate can be chemically treated on one or more surfaces prior to depositing a wet film matrix on it. Desirably, the substrate is substantially flat, but flexible to allow rolling, such as for storage or packaging of the formed film product. The substrate is one or more barriers, such as those disclosed in U.S. Patent Application No. 12 / 711,883 for simultaneous continuation by the Applicant filed February 24, 2010, which is incorporated herein by reference. May include. In some embodiments, the substrate may comprise a preformed sheet of soluble and / or ingestible film, where the wet film forming matrix is deposited on the sheet and is a multi-layer film. Providing the product. In yet another embodiment, the substrate may contain a plurality of preformed film products on its surface, and the wet film matrix is deposited on the surface of the preformed film products.
The substrate may have any desired length and width, depending on the size of the equipment used to process the film. The length of the substrate is not significant, as the substrate can generally be supplied on a continuous substrate within the film forming apparatus and thus can be dimensioned by the user. The width of the substrate is dimensioned to be fed into the equipment used and can be varied as desired. The width of the substrate generally determines the width of the film product that can be prepared on the substrate. For example, multiple film strips or individual film products can be prepared on a substrate and arranged in a substantially aligned fashion, and the cumulative width of those film strips or products is desired. Determine the width of the substrate. Therefore, it is common that the size of the batch determines the cumulative width of the film and also the optimum width of the substrate. The width of the individual film strips or products may be relatively small, ranging from about 2 mm to about 30 mm, for example. The width of the individual film strips may be from about 2 mm to about 10 mm, or from about 10 mm to about 20 mm. In some examples, it may be desired that the individual film strips contain a width greater than 30 mm. It is understood that the "width of individual film strips" is intended to be an average width and that there may be some variation between the individual film strips formed through the present invention. Should be.
Any number of individual film strips or products can be deposited on the substrate. In some embodiments, about 2 to about 30 individual film strips or products can be deposited on the substrate, the film strips or products being spaced apart from adjacent film strips. Arranged in a virtually side-by-side style. In some embodiments, about 10 to about 20 individual film strips or products may be on the substrate. For example, it may be desired that only one film strip or product deposits on the substrate during a test run or other experimental procedure. Desirably, the width of the substrate is at least 2.54 cm (1 inch) wider than the cumulative width of the dried film strips or products and any gaps between them. Having a substrate wider than the cumulative width of the dried film strips or products and the gaps between them allows some durability during processing in processing one or more products. It is useful for doing so.
During use, a wet film forming matrix is deposited on the top surface of the substrate, as described in more detail below. In a preferred embodiment, the wet matrix is deposited on the substrate via extrusion, whereas the wet matrix is deposited on the substrate via any desired means, including coating, casting, thermal spraying, or other means. You may. The wet matrix may be deposited in one contiguous piece or piece, resulting in a dry film piece, which can then be cut into several smaller individual dosages. Alternatively, the wet matrix may be deposited in disparate amounts, as a wet matrix deposited with a width and length that can be dried to form individual film products with the desired width and length. Good.
When deposited on the top surface of the substrate, the deposited wet matrix is dried via any desired drying means, including but not limited to the methods specified in the patents and applications previously incorporated for reference above. be able to. For example, the film matrix provides a viscoelastic aggregate within the first about 0.5 to about 4.0 minutes, resulting in rapid drying in the dryer to "lock in" the components of the film forming matrix. Can be done. The resulting viscoelastic aggregate may then be further dried to provide the final film product. One advantage of drying the film product on the surface of the substrate is that the film can be dried quickly and effectively, resulting in a film having a substantially flat morphology. In addition, the film may become attached to the surface of the substrate during drying, which contributes to the packaging and distribution of the final product. If desired, the resulting dried film product and the substrate on which the product is deposited can be die-cut and packaged together, resulting in film formation from the substrate prior to packaging. Minimize the requirements for removing things. For example, it may be desirable that the film product remains attached to the substrate and that the film product / substrate product be provided to the end user. For example, the methods of the invention are concomitantly continued by Applicant filed February 24, 2010, entitled "Device And System For Determining, Preparing And Administering Therapeutically Effective Doses," which is incorporated herein by reference. It may be useful in forming contiguous pieces of film product that can be rolled and distributed through devices such as those described in the application, US Patent Application No. 12 / 711,899.
With reference to the figures, the present invention provides systems and methods for effectively and continuously producing film products, particularly individual film products or film strips, with minimal waste. The film products formed through the present invention provide high content uniformity and thus provide film products with very accurate dosages. In one embodiment specified in FIG. 1, a film forming apparatus 10 is provided. The film forming apparatus 10 includes a base material 20. As mentioned above, the substrate may be formed from any desired material, including, for example, mylar, paper, plastic, metal, foil, and combinations thereof. If desired, the base material 20 may be laminated. In addition, the substrate 20 can be chemically treated prior to depositing a wet film matrix on it. Desirably, the substrate 20 is substantially flat but flexible to allow rolling.
In some embodiments, the substrate 20 comprises a sheet of preformed film (such as an ingestible film or other biocompatible film product that can be applied to one or more body surfaces). It may be. The preformed sheet of film may be self-supporting and may be supplied via the device, or may be pre-formed on another substrate, whereby both are supplied via the device. To. The base material 20 includes a top surface and a bottom surface (not shown). In this embodiment, the wet film matrix can be deposited on the top surface of the substrate 20. In an embodiment in which the substrate 20 is a sheet of preformed film, the deposition of a wet film forming matrix on the substrate provides a multi-layered film product, with the preformed film being the first layer (or " A backing layer), where the deposited film-forming matrix forms a second layer (or "active ingredient layer"). Although both layers can contain the active ingredient, it may be useful that the first layer does not contain the active ingredient but the second layer contains the active ingredient. The resulting multi-layer film can then be sized and cut to provide the individual multi-layer film products. In yet another embodiment, the substrate 20 may be a sheet of non-ingestible product (ie, paper, mylar, etc.), the substrate being formed on its upper surface in advance of a plurality formed therein. Contains ingestible film products. In this aspect, the wet film matrix may be deposited on top of the preformed film product. This embodiment forms a multi-layer film product without the need for further dimensioning or cutting of the multi-layer film product. In a further embodiment described in more detail below, the apparatus 10 comprises the substrate 20 prior to the deposition of a second layer (or multiple layers) of the film product onto the first layer of the deposited film product. Means may be included to form a first layer of film product on the top surface.
The base material 20 may be stored as a continuous roll of the base material 20 prior to use. During use, the first end of substrate 20 (not shown) is fed into device 10 in the direction indicated by arrow A. As described in more detail below, the substrate 20 can move continuously in direction A during use, during which the wet film matrix is deposited on the top surface of the substrate 20 during the drying process. Is guided along the direction A. The substrate 20 can move at any desired rate of speed. The speed at which the substrate 20 moves can be varied as needed to meet the drying needs of the film-forming material, taking into account the desired dryer temperature. For example, if a longer drying time is desired, the substrate 20 can move through the device 10 at a slower rate. If shorter drying times are required, the substrate 20 can move through the device 10 at a faster rate. In addition, in some embodiments, the rate of action can control the thickness of the wet film product to deposit. For example, in the extrusion process, a faster rate of substrate 20 results in a thinner wet film product on its surface and vice versa. As mentioned above, the substrate 20 may have any desired length or width. Desirably, the width of the substrate 20 is sufficient to allow the deposition of multiple individual film products arranged in a substantially aligned pattern. For example, the substrate 20 may be wide enough to allow the deposition of about 2 to about 30 individual film products arranged substantially side by side. The individual film products may have gaps between adjacent film strips to allow for easier processing and dispersion.
The device 10 includes a container 30 designed to contain a predetermined amount of film forming matrix. The film-forming matrix includes any desired film-forming component, including, for example, polymers, solvents, sweeteners, active ingredients, filters and the like. Ingredients useful in the film formation matrix include those disclosed in US Publication No. 2005/0037055, which is incorporated herein by reference in its entirety. Container 30 may include two or more separate storage boxes or dividers for storing the various components of the film forming matrix. For example, it may be desired to store the active ingredient rather than the solvent or polymer in a separate container until just before deposition on the substrate 20. The container 30 is preferably pressurized so that the film forming matrix can be effectively forced into it via the device 10. In some embodiments, the device 10 has the ability to extrude a film-forming matrix, as described in more detail below. In such an embodiment, it may be desired that the film forming matrix have a high viscosity and / or a high solid content. For example, the film-forming matrix may contain at least 30% solids, or may contain at least 25% solids, or may contain at least 20% solids. In other embodiments, the matrix may be a slurry or solid suspension in a fluid carrier. The devices 10 and methods described herein allow the processing of film forming matrices with such high solids without the risk of failure or blockage within the system. Alternatively, the film-forming matrix may have a low solid content and even a lower viscosity if desired. It is generally preferred that the film-forming matrix be sufficiently viscous to maintain its shape after deposition of the substrate 20 on the surface.
Attached to the vessel 30 is a feed line or tube 40 that fluidly connects to the vessel 30 and connects the vessel 30 to a plurality of volumetric pumps 50, 50'. The feedline 40 may be made from any desired material and may have any desired thickness or radius. The feed line 40 is sufficient to effectively carry the film forming matrix from container 30 to volumetric pump 50 without showing sufficient pressure drop with respect to blockage, clogging, or inadequate supply of material to the pump. It is preferable to have a radius. The device 10 may include any desired number of volumetric pumps 50, depending on the number of individual film products the user wishes to produce. In one embodiment, each volumetric pump 50 in device 10 is used to form a film product, so the number of volumetric pumps 50 used can determine the number of film products formed. .. The volumetric pumps 50 are preferably arranged in a lined pattern within the device 10. The feedline 40 preferably supplies the film forming matrix from the vessel 30 to the volumetric pump 50 in a parallel style, thus supplying each volumetric pump 50 with a film forming matrix on a substantially uniform basis. Enables.
The volumetric pump 50 may be any type of pumping device desired by the user. Desirably, the volumetric pumps 50 are of approximately equal size and shape, respectively, and have the ability to distribute substantially the same amount of film forming matrix from it. It is particularly desirable to use a pump 50 capable of distributing a known amount of matrix per pumping cycle. In addition, the pump 50 should have the ability to be replenished with the film forming matrix after a predetermined amount of film forming matrix has been distributed via pumping. In particular, it is desired that the pump 50 be replenished with substantially the same amount of film forming matrix after each pumping cycle. Therefore, each pumping cycle (including one film-forming matrix distribution and one film-forming matrix replenishment) should contain a substantially constant amount of film-forming matrix. As can be understood, regardless of the type of pump used, the pump 50 is an accurate and consistent wet film to ensure substantial uniformity between each of the resulting film products. It is important to provide the distribution of the matrix.
In one embodiment, the volumetric pump 50 is a piston pump. If desired, the volumetric pump 50 may include a dual piston pump, and as the pump 50 distributes an amount of film forming matrix, the pump 50 is simultaneously replenished with another volume of film forming matrix. In other embodiments, the volumetric pump 50 may include a gear pump. A dual piston pump is particularly desired for the formation of film-containing patches. The device 10 may include one or more combinations of at least one piston pump, at least one dual piston pump, and at least one gear pump. Because piston pumps and compound piston pumps have the ability for such pumps to "suck back" after the wet film matrix has been pumped out of it, thus preventing or reducing its amount of sagging. Especially preferable. Further, the piston pump and the compound piston pump provide the ability to continuously load and push the wet film forming matrix as the substrate 20 moves. These pumps are efficient and also avoid the requirement to move the head manifold back and forth, which is required for typical systems. In some embodiments, the volumetric pump 50 may have variable stroke and / or variable speed settings. That is, the volumetric pump 50 may have a variable stroke, allowing the user to modify the stroke associated with the pump 50 to meet specific needs.
In some embodiments, the volumetric pump 50 may distribute any amount from about 4 microliters per stroke to about 100 microliters per stroke. In addition, the volumetric pump 50 may be a variable speed pump to allow the user to set a particular speed desired for the particular film product being formed. For example, if a longer drying time is desired by the user, the volumetric measuring pump 50 may be set to a slower distribution rate, allowing for longer steps and thus longer drying times. Alternatively, a faster speed pump may be desired for shorter drying times. The speed and stroke of the volumetric pump 50 may be related to the speed at which the substrate 20 moves within the device 10.
The volumetric pump 50 used herein should be properly dimensioned to provide the desired film volume. In particular, the volumetric pump 50 should be sized to fill and distribute a sufficient amount of film forming matrix to form one individual film product with the desired volume. For example, in one embodiment, the dry individual film product resulting from the desired result may have a total weight of about 1 mg to about 20 mg. In some embodiments, the individual dried film products may have a total weight of 60 mg or less. It is understood that the weight of the wet film product is heavier than the resulting dry film product due to the loss of certain volatiles. The volumetric pump 50 should be capable of distributing from about 3 microliters to about 250 microliters per pumping cycle, or less than 250 microliters per pumping cycle. For percutaneous systems, the individual dry film products that result as desired may have a total weight of about 10 mg to about 2000 mg. Thus, the volumetric pump 50 should be capable of distributing about 30 microliters to about 10 milliliters per pumping cycle to provide the weight of the dry film that results as desired. In another embodiment, the volumetric pump 50 can be a capacitive pump. Examples include uniaxial thread pumps, also known as uniaxial eccentric thread pumps, eccentric thread pumps, or even mere cavity pumps. One particular example of this type of pump is the Moyno® pump (Moyno). Additional capacitive pumps include gear pumps, rotary lobe pumps, piston pumps, membrane pumps, screw pumps, hydraulic pumps, vane pumps, regenerative (overflow) pumps, and peristaltic pumps. The system of the present invention may include one or more of the aforementioned positive displacement pumps 50.
Each of the volumetric pumps 50 is preferably associated with a covered head manifold 60 that includes a plurality of orifices 70, 70'. Desirably, each volumetric pump 50 is associated with one individual orifice 70. The volumetric pump 50 is fluidly connected to the associated orifice 70, thus allowing the film forming matrix to be pumped out of the pump 50 through the orifice 70. In one particular embodiment, the orifice 70 is a slot die, but the orifice 70 may be any other desired opening or die. The orifice 70 is preferably dimensioned to allow the formation of the desired film product.
The orifice 70 preferably communicates with the substrate 20 such that when a particular amount of wet film forming matrix is distributed through the orifice 70, the wet film forming matrix is deposited on the top surface of the substrate 20. Thus, in one embodiment, the manifold 60 has a first side 65A and a second side 65B, and the orifice 70 extends from the first side 65A to the second side 65B through the manifold 60. ing. Pump 50 is in contact with 65A on the first side of the manifold. The wet film matrix is pumped from the vessel 30 through the feedline 40, through the pump 50, through the orifice 70, and deposited on the substrate 20 moving in the working direction A. It is particularly desired that the wet film matrix is extruded directly onto the substrate 20 through the orifice 70 and therefore the wet film matrix should have a sufficiently high viscosity and / or solid content to allow extrusion. Will be done. In addition, the wet film forming matrix should be sufficiently viscous to generally maintain its shape and size after deposition of the substrate 20 on the surface. Of course, it is considered that the matrix may have a lower viscosity instead, and that the matrix may simply flow through the orifice 70 onto the substrate 20. The substrate 20 may have separate barriers, recesses, or pockets formed therein, in which a wet film forming matrix can be deposited.
In one embodiment, a plurality of individual wet film products 80, 80'are deposited on the surface of substrate 20 in a substantially aligned manner. The individual wet film products 80 are deposited on the substrate 20 as the substrate 20 moves through the apparatus 10, preferably each individual wet film product 80 is an individual wet film product already extruded. The object 80 is extruded onto one region of the non-existent substrate. As such, the substrate 20 may have a plurality of individual wet film products 80 deposited along its length and width. Each individual wet film product 80 is sized to provide the desired final dry film product. The rate at which the substrate 20 moves during the deposition of the wet film product 80 on its surface can determine or control the size of the wet film product 80. In particular, the thickness of the wet film product 80 can be controlled by the speed of the substrate 20, the faster moving substrate 20 provides the thinner wet film product 80, and vice versa. During use, each pump 50 dispenses a plurality of individual wet film products 80 into lanes (85A, 85B, 85C) on substrate 20. Each lane (85) contains a plurality of individual wet film products 80. Desirably, each of the individual wet film products 80 has a substantially uniform size, shape, and content. In this style, the known dosage between each of the individual wet film products 80 can be known fairly accurately. The individual wet film product 80 can be deposited directly on the non-film substrate 20, or the individual wet film product 80 can be deposited on the substrate 20, which is a preformed film. (Thus forming a multi-layer film product). It is desired that the volumetric pump 50 repeatedly dispenses the individual wet film products 80 onto the surface of the substrate 20 so as to form lanes 85 of the individual wet film products 80.
Any number of individual wet film products 80 can be deposited on the surface of substrate 20. The number of lanes 85 of the wet film product 80 depends on the number of pumps 50 and orifices 70 in device 10. For example, if device 10 includes five pumps 50 and associated orifices 70, five lanes 85 of the wet film product 80 formed on the substrate 20 occur. Any number of pumps 50 and orifices 70 can be used in device 10, and preferably there may be about 2 to about 30 pumps 50 and orifices 70 in device 10. Thus, there may be about 2 to about 30 lanes 85 of the individual wet film products 80 formed on the substrate 20. There may be any number of individual wet film products 80 per lane 85, depending on the speed of the pump 50 and the speed of the substrate 20. Desirably, there is a slight gap between each individual film product 80 within the lane 85, as well as a small gap between each adjacent lane 85, as depicted in FIG. The gaps between the individual wet film products 80 can contribute to the processing and later to the packaging of the resulting film products. As mentioned above, the substrate 20 may contain an ingestible film product preformed on its surface, and the wet film product 80 is deposited directly on the top surface of the preformed film product. Can be done. The preformed film product on the substrate may be a sheet of continuous film. Alternatively, in some embodiments, the substrate 20 may have a plurality of individual film products preformed on its surface, and the wet film matrix (forms a multi-layer film product). (Like) deposits on the surface of the individual film products preformed on the substrate 20. In this style, the multi-layer film product is formed with little or no cutting and dimensional measurement required, as the individual multi-layer film products can be simply removed from the substrate 20 when dried. be able to.
The individual wet film product 80 may have any desired shape, including squares, rectangles, circles, or other desired shapes. The individual wet film product 80 may be of any desired size, depending on the size of the dry film product resulting from the desired result. In some embodiments, the wet film product 80 may be a small film product, i.e., each having a mass of about 1 mg. The individual film products 80 may have a higher mass, such as about 1 mg to 200 mg, per individual film product, if desired. The individual film product 80 may be 200 mg or less, or 100 mg or less. For a percutaneous system, the individual film product 80 can range from about 10 mg to about 2000 mg and / or less than 2000 mg or less than 1000 mg.
As described above, the substrate 20 moves in the direction A during the manufacturing process. The rate of substrate 20 determines the number of individual film products that deposit on substrate 20 during processing, as well as the rate of velocity of pump 50. Even after the individual film products 80 are deposited on the substrate 20, the substrate continues to move in direction A towards the drying device 90, such as a dryer. The wet film product 80 may be dried via any desired mode, such as the drying method described above. After the drying step is complete, multiple dried individual film products can be removed from the substrate and further packaged for dispersion. Alternatively, the substrate 20 with the dried film product can be rolled up and stored for future use. In yet another embodiment, the individual dried film products can be die-cut with substrate 20 and packaged for dispersion. In particular, in embodiments where the substrate 20 comprises a film preformed on its surface, it may be useful to cut the individual film products that have been dried to form a cut multi-layer film product. .. Desirably, no preformed film product on the substrate 20 and its surface can contain any active ingredient when the dried film product will be cleaved from the substrate 20. As such, the rest of the material from which the individual film products are cut can be discarded without wasting possibly expensive material, including the active ingredient.
In another embodiment depicted in FIG. 2, device 110 can be used to form contiguous pieces or lanes of film product 180. The formation of strips of continuous film product 180 can be useful in devices that distribute rolls of continuous film, such as those described above. In addition, the formation of pieces of continuous film product 180 can be beneficial for storage, packaging, and / or dispersion purposes. As mentioned above, the wet film fragment product 180 may be a non-film substrate (ie, the Mylar, paper, etc. described above) or may contain a preformed film on its surface. Accumulate on 120. The substrate 120 passes through the apparatus 10 in the direction marked by arrow A, as described above. The device 110 includes a container 130 that can be pressurized, as described above. Container 130 is designed to contain the film forming matrix. If desired, the container 130 may include two or more dividers, thus containing the various film-forming components separately until just prior to the formation of the film product, i.e. the solvent and the solvent separately added from the active ingredient. Has the ability to release the polymer.
The feed line 140 is connected to the container 130, which is connected to a plurality of volumetric pumps 150, 150'. The volumetric pump 150 may be any desired pump mechanism, preferably a pump mechanism that allows continuous and even distribution of the wet film matrix from it. By distributing an even and continuous amount of the wet film matrix, uniform film product 180 strips can be formed on the surface of the substrate 120. It is particularly desired that each piece of film product 180 contains a substantially uniform amount of content per unit area, including a known amount of active ingredient per unit area. Each strip 180 should have substantially the same thickness, width, and viscosity to provide a substantially uniform final film product. Therefore, the volumetric pump 150 should have the ability to distribute a substantially uniform and continuous amount of wet film product. In a desired embodiment, the volumetric film pump 150 is a gear pump or metering pump. Any known gear pump and / or metering pump in the art can be used.
Desirably, any number of volumetric pumps 150 arranged in a substantially side-by-side fashion as shown in FIG. 2 may be in device 110. Preferably, there is a space or gap between each volumetric pump 150, which contributes to the processing of the film product and the subsequent recovery and packaging. The size of the gap between adjacent volumetric pumps 150 should be large enough to allow ease of manufacture, but large enough to reduce the number of pumps 150 available in device 110. No need. The number of volumetric pumps 150 determines the number of strips of film product 180 formed by device 110. For example, there may be about 2 to about 30 volumetric pumps 150 in the device, more preferably about 10 to about 20 volumetric pumps 150 in the device. Each volumetric pump 150 is fluid connected to the vessel 130 via a feedline 140 so that the film forming matrix is provided from the vessel 130 to the pump 150 on an even and continuous basis during operation. During operation, the amount of film forming matrix provided to the volumetric pump 150 located closest to the vessel is substantially equal to the amount of film forming matrix provided to the volumetric pump 150 located farthest from the vessel. Should be. This ensures that the resulting strips of film product 180 have a substantially uniform content across the strips 180.
Each volumetric pump 150 is associated with a first side 165A of the manifold 160 so that the film forming matrix can be distributed through the manifold 160. Manifold 160 includes a plurality of orifices 170 extending through it. The orifice 170 extends from the first side 165A to the second side 165B through the manifold 160. In a preferred embodiment, each orifice 170 is fluidly connected to one volumetric pump 150 so that the film forming matrix can be distributed from one volumetric pump 150 through one orifice 170. Therefore, the number of orifices 170 should be equal to the number of volumetric pumps 150. In a desired embodiment, the orifice 170 is a slot die, but the orifice 170 may be any desired opening, through which a wet film forming matrix can be supplied. It is further desired that each orifice 170 be approximately the same size as each other, including approximately the same height, width, length, and shape. In this style, the resulting strips of film product 180 will each have a substantially uniform shape, size, and content.
During use, each volumetric pump 150 distributes a wet film forming matrix through a manifold 160 via an orifice 170. The wet film forming matrix is deposited directly from the orifice 170 onto the surface of the substrate 120. During processing, the substrate 120 is moved in direction A along the device 110. It is particularly desirable to use a volumetric pump 150 capable of continuously distributing the film forming matrix during the manufacturing process so as to form the strips of the continuous film product 180. The rate of movement of the substrate 120, along with the distribution rate of the volumetric pump 150, controls the amount of wet film forming matrix deposited on the surface of the substrate 120. For example, it may be desired that the substrate 120 move at a slower rate if the wet film forming matrix is very viscous. Alternatively, it may be desired that the substrate 120 move at a faster rate, for example if the wet film forming matrix is of lower viscosity. The substrate 120 moves in direction A from the manifold 160 to a drying device 190, such as a dryer or other means for drying the wet film matrix. The speed of the substrate 120 and the size of the drying device 190 will determine the length of time that the wet film product 180 is dried in the drying device 190. For example, using a faster moving substrate 120 and / or a shorter drying device 190, the wet film product 180 dries for a shorter period of time than using a slower moving substrate 120 and / or a longer drying device 190. Be made to.
The individual wet film product 180 strips are preferably arranged in rows (ie, 185A, 185B, 185C) along the longitudinal direction of the surface of the substrate 120. Fragments of wet film product 180 are arranged in a substantially aligned fashion with sufficient space or clearance between adjacent lanes 185 to contribute to the processing and subsequent recovery / packaging of the film product. Is particularly preferable. There may be as many rows 185 as desired, and each row 185 is formed by an individual volumetric pump 150 and an associated orifice 170. In addition, the space between each adjacent row 185 is approximately equal to the space between adjacent orifices 170 in device 110. Each row 185 of the film material is preferably a lane of continuously deposited wet film matrix so that individual rows 185 of the dried film product can be recovered and packaged after the drying is complete. .. For example, it may be desired that the individual rows 185 be removed from the substrate 120 and rolled up and placed in a distributor for use by the end user. Alternatively, row 185 can be cut with substrate 120 to provide a continuous strip of film 185 with substrate support. In addition, the dried film strip 180 can be cut into individual film products of approximately equal size and shape, each individual film product being a single unit dose.
In one particular embodiment depicted in FIGS. 3A and 3B, the device can be useful in forming a series of individual multi-layer products. For example, the individual multi-layer products may include active ingredient-containing patches. The above-mentioned device represented by FIG. 1 is particularly useful in forming individual multi-layer products such as patches. In this embodiment, the substrate 210 may include a sheet of ingestible and / or soluble film 220 (also referred to herein as the "first layer") that forms a backing layer against the active ingredient-containing layer. In some embodiments, the ingestible film 220 sheet may be the substrate 210, such as when the ingestible film 220 sheet is self-supporting and capable of being fed through the device itself. The first layer 220 is preferably made of a mucosal, biocompatible and soluble material. It may be desired that the first layer 220 be a slowly melting film sheet. By "melting slowly", it is intended that the sheet 220 has a dissolution rate longer than the rate of the active ingredient-containing layer adhering to it (below). The first layer 220 can be formed on another substrate, such as the Mylar, paper, or other ingestible backing layer described above. The first layer 220 may be formed and dried in advance, may not be dried, or may be partially dried. For example, the first layer 220 may be a viscoelastic aggregate of the film-forming material.
The first layer 220 has a first surface 225. During processing, as described above, the plurality of individual active ingredient-containing wet film layers 230 (also referred to herein as the "second layer") are placed on the first surface 225 of the first layer 220. accumulate. Desirably, the active ingredient-containing wet film layer 230 is made from a biocompatible polymeric material that melts faster than the first layer 220. As described above, the active ingredient-containing wet film layer 230 preferably has the desired gaps between adjacent active ingredient-containing wet film layers 230 in a manner substantially aligned via a plurality of volumetric pumps. And deposit. After the individual active ingredient-containing film layers 230 have deposited and dried on the first layer 220, the two layers (220, 230) should be sufficiently adhered to each other so that they do not separate. The two layers 220, 230 may be sufficiently adhered to each other in the drying step alone, or an adhesive formulation may be applied between the first layer 220 and the active ingredient-containing film layer 230. ..
Once the active ingredient-containing film layer 230 (and optionally the first layer 220) has dried sufficiently, the first layer 220 can be dimensioned and cut. In one embodiment, the sheets of the soluble film 220 form a series of individual multi-layer products 260 in a first direction 240 (between adjacent active ingredient-containing film layers 230) and a first direction. It is cut (between adjacent active ingredient-containing film layers 230) in a second direction 250, which is substantially perpendicular to 240. As can be seen in FIG. 3B, the multi-layer product 260 comprises a first layer 220 and a second layer 230 attached thereto. The first layer 220 preferably melts slower than the second layer 230. The second layer 230 preferably contains at least one active ingredient. If desired, the first layer 220 may contain at least one active ingredient, which may be the same as or different from the active ingredient in the second layer 230. In one embodiment, the second layer 230 is determined to be smaller in size than the first layer 220, i.e. the length and / or width of the second layer 230 is the first to combine. It is preferably less than the length and / or width of layer 220. In this style, at least a portion of the first side 225 of the first layer 220 is exposed beyond the sides of the second layer 230. It is particularly preferred that a portion of the first side 225 of the first layer 220 be exposed around the entire perimeter of the second layer 230. For example, as depicted in FIG. 3B, the second layer 230 may have a length and width smaller than that of the first layer 220, and the second layer may be of the first layer 220. It can generally be deposited in the center. Thus, the first side 225 of the first layer 220 is exposed around the entire perimeter of the second layer 230. Alternatively, the width and / or length of the first layer 220 and the second layer 230 may be approximately equal. In another embodiment, one or more sides of the first layer 220 and the second layer 230 may be coplanar to each other.
It can be said that at least the first side 225 of the first layer 220 can be made from a mucosal adhesive material so that it can be fully applied and adhered to the mucosal surface of the user's body. preferable. For example, the resulting multi-layer product 260 can be applied to any skin surface of the user, for example, a mucosal surface including the surface of the user's mouth, nose, eyes, vagina, or anus. Alternatively, it can be applied to internal organs during surgery. In this embodiment, the individual multi-layer product 260 is applied by the user to the skin surface such that the first side 225 of the first layer 220 comes into contact with and substantially adheres to the skin surface. be able to. In this embodiment, the active ingredient-containing layer 230 is directed to the user's skin surface. If the second layer 230 melts faster than the first layer 220, the second layer 230 may be allowed to melt well towards the user's skin surface, the second layer 230. Allows complete absorption of any one or more active ingredients contained in the user into the body. Unsurprisingly, the multi-layer film product aspect described above is as opposed to the individual active ingredient-containing film layers 230 (as depicted in FIG. 2 and as described above) in detail of the continuous active ingredient-containing film product. It is understood that it can be formed with pieces. In such an embodiment, the product is cut in such a style so that the two opposite sides of the first surface 225 of the first layer 220 are exposed beyond the strips of the second layer. You may.
In another aspect depicted in FIG. 4, the device 310 may include a first film forming region 310A and a second film forming region 310B. In such an embodiment, the first film forming region 310A may include a first container 315 containing the first film forming matrix. The first film-forming matrix generally contains a film-forming component as described above, and may further contain an active ingredient or may be free of an active ingredient. Device 310 includes a substrate 320 made from ingestible materials such as the Mylar, paper, and other materials described above. The substrate 320 moves through the device 310 from the first film forming region 310A to the second film forming region 310B in the direction indicated by the arrow A, as in the other embodiment described above. The first film forming region 310A is intended to be in fluid contact with the first container 315 and to deposit a continuous sheet 330 of the first film forming material on the substrate 320 during use. Includes first manifold 325. Optionally, a first drying device (not shown) may be placed after the first manifold 325 but in front of the second film forming region 310B. During use, the apparatus 310 deposits a sheet 330 of the first film-forming material on the substrate 320 to form a first layer of the film-forming material. Sheet 330 of the first film-forming material may be desired to be dried just before entering the second film-forming region 310B. Alternatively, the sheet 330 of the first film-forming material may be partially dried before entering the second film-forming region 310B, for example to form a viscoelastic aggregate of the film material.
The first layer 330 of the film-forming material moves through the device 310 (whether dried, undried, or partially dried) into the second film-forming region 310B. The second film-forming region 310B may include the components and methods described above with respect to the embodiments depicted in FIG. 1 or 2. For example, the second film forming region 310B includes a second container 340 that communicates fluidly with the second feedline 345. The second feed line 345 communicates with multiple volumetric pumps 350. The plurality of volumetric pumps 350 communicate with a second manifold 355 containing the plurality of orifices 360. As mentioned above, preferably, each orifice 360 is coupled to one volumetric pump 350. The second film-forming region 310 deposits a plurality of wet film products 365 in a series of rows (ie, 370A, 370B) in a manner substantially aligned on the first layer 330 of the film-forming material.
The first layer 330 of the film material and the plurality of wet film products 365 move through device 310 into drying device 375, which may be a dryer. The wet film product 365 (and optionally the first layer of film) is dried, such as by the drying method described above. When sufficiently dried, the resulting multi-layer film product (including the first layer 330 and multiple now-dried film products 365) is dimensioned and cut as desired, or or Can be stored for future use. The first layer 330 and the film product 365 preferably adhere to each other, which can be simply achieved through a drying step, or the first layer 330 and the film product prior to its deposition. Adhesive formulations may be applied to and from 365.
The present invention takes into account and presupposes an understanding of many problems that can adversely affect the flow of material through the slot die and cause changes in the flow of material. Small changes in certain parameters, although not desirable, change the resulting film content uniformity, especially the uniformity of the active ingredient produced across multiple slot dies fed from a single pump. sell. Content uniformity between individual films or medications, especially the uniformity of the active ingredient, is of particular importance in film production. The present invention minimizes or eliminates all possible problems associated with the use of a single pump, as described below. In a general system and in the present invention, a preferred slot die is a rectangular orifice having three dimensions, height (B), width (W), and length (L). The length (L) is understood to be the length of the orifice from the front to the back of the die as the length from the first side 65A to the second side 65B, as depicted in FIG. The flow through a rectangular die, such as the slot die of the present invention, can be defined by the Hagen-Poiseuille equation.
<maths num="1"><img id="000002" he="12" wi="88" file="JP5977751B2_D0001.tif" img-format="tif" img-content="drawing" /></maths> In the above equation, Q is the volumetric flow rate, P is the pressure, and μ is the viscosity of the fluid flowing through the die. When a large number of orifices flow through a common device, such as a slot die coater with a single pump that supplies a large number of slot dies to the manifold, the flow rate can be adversely affected by many factors. Even the slightest variation in these factors may have a significant influence on the flow rate and therefore on the content of the film formed by the device. The possible disadvantages of such a system are reduced or eliminated through the present invention. For example, a change in pressure can affect the flow rate because the flow is proportional to the pressure at the entrance to the slot in the slot die. If a substantially uniform flow is desired across multiple slot dies, it is important to have substantially equal pressure levels at the inlet to each slot die. To achieve this equal pressure level across all dies, the design of the manifold with a single pump to supply it must prevent the flow inside the manifold from being disturbed by external forces. That is, the flow in such a manifold must not be disturbed by changes in temperature, viscosity, or non-uniform distribution or agglomeration of components in the flowing fluid. In addition, the height of the slot die may have an effect on the flow rate of the fluid flowing through it. The flow is proportional to the cube of the slot height, which is generally the narrowest dimension of the slot die. Since this is generally the smallest size, any change in this size from slot to slot is supplied to each of the slot dies, thus potentially relative to the rate of change in the flow rate of the matrix. Has a high influence on. To negate this problem, it is important that each of the slot dies in the device have the same height and size as each other. Even a 3% difference in height between adjacent slot dies in the device causes a variation of nearly 10% in flow rate.
Another factor that can affect the flow rate is the viscosity of the fluid flowing through the die. The flow rate is such that changes in local viscosity due to forces such as temperature or non-uniformity (aggregation of particles in the matrix) affect the flow rate through that slot and later to the remaining slot dies. As such, it is inversely proportional to viscosity. Even the slightest change in flow rate can adversely affect the uniformity of the active ingredient content of the film formed by the later slot dies. In the present invention, the flow rate through each individual slot die is determined and controlled by the flow exiting the individual volumetric pumps attached to the individual slot dies. The present invention overcomes the above problems by using a plurality of individual pumps coupled to individual slot dies. Pressure can be maintained at a substantially constant level between each individual pump. In addition, since each slot die is coupled to an individual pump, variations in height between adjacent slot dies have no influence on each other. Finally, the use of individual pumps can easily take into account changes in viscosity and minimize any potential impact based on those changes.
While the above problems can potentially be solved through the use of manifolds supplied by a single pump directed to multiple individual slot dies, such devices are affected by any external force. Must include non-manifold, identical slot dies, and viscosity of the flushed matrix that is perfectly uniform with no loss of viscosity from the first slot die to the last slot die. Such devices are cumbersome and difficult to obtain.
As can be correctly understood by those skilled in the art, the present invention provides systems and methods for providing each slot die with its own individual pump to address the problems associated with such single pump equipment. This will substantially solve the problem. The system allows for better control and stability between slot dies within the system. The possible problems specified in the Hagen-Poiseuille equation above are amended using the present invention in an efficient and controlled manner. The result is a more predictable and uniform product between each slot die in the system. Many aspects of the invention have been described. Nevertheless, it is understood that various modifications can be made without departing from the spirit and scope of the invention. Further, the above steps can be modified in various ways, as appropriate, or can be performed in a different order than above. Therefore, another aspect is also within the scope of the present disclosure.
6 sheets
Sheet 1 Sheet 2 Sheet 3 Sheet 4 Sheet 5 Sheet 6
Every citation, both ways
| Document | Relation | Office |
|---|---|---|
| US20060169205A1 | Cites | United States of America |
| JP63141923A | Cites | Japan |
| JP2000233151A | Cites | Japan |
| JP07500531A | Cites | Japan |
31 members in 9 offices
Priority claims9
| Document | Office | Kind | Date |
|---|---|---|---|
| 12909995 | United States of America | – | |
| 90999510 | United States of America | A | |
| 90999510 | United States of America | A | |
| 2011057233 | United States of America | W | |
| 2011057233 | United States of America | W | |
| 12909995 | – | – | – |
| US20100909995 | – | – | – |
| US2011057233 | – | – | – |
| WO2011US57233 | – | – | – |
Members31
| Document | Office | Kind | |
|---|---|---|---|
| CA2815467A1 | Canada | A1 | |
| CA3049346A1 | Canada | A1 | |
| US2012100202A1 | United States of America | A1 | |
| WO2012054810A2 | World Intellectual Property Organization (WIPO) | A2 | |
| WO2012054810A3 | World Intellectual Property Organization (WIPO) | A3 | |
| AU2011316903A1 | Australia | A1 | |
| EP2629947A2 | European Patent Office (EPO) | A2 | |
| CN103298590A | China | A | |
| JP2013540161A | Japan | A | |
| KR20140022766A | Republic of Korea | A | |
| EP2629947A4 | European Patent Office (EPO) | A4 | |
| US9149959B2 | United States of America | B2 | |
| CN103298590B | China | B | |
| US2016089826A1 | United States of America | A1 | |
| JP5977751B2This record | Japan | B2 | |
| JP2016204381A | Japan | A | |
| KR101937457B1 | Republic of Korea | B1 | |
| KR20190007091A | Republic of Korea | A | |
| EP2629947B1 | European Patent Office (EPO) | B1 | |
| US10272607B2 | United States of America | B2 | |
| KR102005223B1 | Republic of Korea | B1 | |
| CA2815467C | Canada | C | |
| JP2019171379A | Japan | A | |
| US2019329476A1 | United States of America | A1 | |
| EP3566841A1 | European Patent Office (EPO) | A1 | |
| ES2732821T3 | Spain | T3 | |
| JP6795926B2 | Japan | B2 | |
| US10940626B2 | United States of America | B2 | |
| CA3049346C | Canada | C | |
| EP3566841B1 | European Patent Office (EPO) | B1 | |
| ES2980992T3 | Spain | T3 |
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Numbers
- Publication
- 5977751
- Publication, DOCDB
- 5977751
- Publication, EPODOC
- JP5977751B
- Application
- 2013535110
- Application, DOCDB
- 2013535110
- Application, EPODOC
- JP20130535110
Titles2
- Japanese
- 小フィルム細片の製造
- English
- Manufacture of small film strips
Classification
- CPC, 21
- A61K9/0014
- B29C48/155
- A61K9/70
- A61K9/006
- A61K9/7084
- B29C31/06
- A61K9/7007
- B29C48/12
- B29C48/08
- B29C48/21
- B29C48/0022
- B29C48/37
- B29C48/154
- B29C48/2556
- B29C48/022
- B29C41/28
- B29C48/285
- B28B3/00
- B29K2105/0035
- B29K2995/0056
- B29C48/28
- IPC, 10
- A61K9 70
- B29C48 155
- B05C5 02
- B29C48 08
- B29C48 12
- B29C48 154
- B29C48 21
- B29C48 28
- B29C48 37
- B29C47 00
