Pharmaceutical preparation in the form of a foil having an active substance incorporated therein
Abstract
The pharmaceutical composition contains one or more pharmaceutical agents dissolved or uniformly suspended in a sheet whose material is soluble in water or organic solvents, preferably in both. It can be produced by dissolving or suspending the agent, introducing a sheet former which is soluble in water and/or soluble in organic solvents, drawing the resulting solution or suspension out to a film and drying the latter. The pharmaceutical sheet obtained in this way is divided into sections, e.g. dosage units. It is also possible to use release agents and fillers as well as the conventional flavourings, colorants etc. in the process.
Term
No projected expiry on record.
- Priority
- Filed
- Granted
- Today
1 claim: 1 independent, 0 dependent
- 1Patentkrav Sätt att fråmställa ett läkemedel i folieform för oral oeh ^topisk användning med en halt av verksam substans upp till 60 vikt? av foliet, kännetecknat av att man löser eller suspenderar den verksamma substansen och eventuellt ett släppmedel i en mängd av 0,01-2 vikti, hänfört till lösningen eller suspensionen, i ett lösnings- eller suspensionsmedel som utgör en mängd av 48-84 vikti, hänfört till lösningen eller suspensionen, och som består av vatten och/eller ett eller flera fysiologiskt fördragbara organiska lösningsmedel-, att man som foliebildare inför hy'droxipropylcelldlosa, hydroxietylcellulosa och/eller metylhydroxipropylcellulosa i en mängd av 6-20 vikti, hänfört till lösningen eller suspensionen, och eventuellt inför ett fyllmedel i en mängd av 0-30 vikti, hänfört till lösningen eller suspensionen, eventuellt homogeniserar och drager ut lösningen resp. suspensionen i en foliedragmaskin till en utstrykning med en skikttjocklek, bestämd på den torra folien, av 0,05-1 mm, företrädesvis r 0,07-0,3 mm, och delar upp den vid torkning av utstrykningen erhållna folien i avsnitt (doseringsenheter).
388 paragraphs in 2 sections, as filed
(54) Name: Methods of preparing a drug carrier in foil form with incorporated active ingredient
The invention relates to a method of preparing a drug carrier in foil form with incorporated active substance for internal and external use.
From Belgian Patent Specification 637,363, paper foils are known which are coated with active substance and are suitable for oral use. The films consist of water-insoluble cellulose fibers and a water-soluble binder. As water-soluble binder, sodium carboxymethyl cellulose is preferably used. The active substance is applied to the paper film by dropping the dissolved active substance or spreading the solid active substance on the film or by drawing the film through a solution of the active substance. The discontinuous process in the separate production of foil and application of active substance has the disadvantage that the dosage precision is not good, which, however, is of great importance for the currently low-dose active substances. Inaccuracies arise not only in the application of the active substance, but also in the preparation and pretreatment of the carrier and through changes in the storage of the carrier material. Thus, for example, it has been found that, according to the formulations of the Belgian patent application, when using foil drawers. no homogeneous film layer is formed and that film
7507659-6 shrinks upon drying. However, it is readily recognized that in a non-uniform material, the uptake of the active substance is not homogeneous.
In addition, a mere active substance fixed on the surface can be used in the handling of the foils, e.g. for packaging, partially re-separated. The sodium carboxymethyl cellulose used as a binder is dissolved in the stomach, thereby releasing carboxymethyl cellulose which partially encloses the active substance and only delays its release or does not release it at all.
It has now been found that films of homogeneous thickness and homogeneous distribution of active substance are obtained when producing films of incorporated active substance and using foil-forming agents which are soluble in water or in organic solvents. In this case, foil formers which are soluble in water as well as in organic solvents are preferably suitable.
The method of the invention for preparing a film in drug form for oral and topical use with a content of active substance up to 60 wt. -2 wt., Attributed to the solution or suspension, in a solvent or suspension agent constituting an amount of 48-84 wt., Attributed to the solution or suspension; and consisting of water and / or one or more physiologically acceptable organic solvents, which as hydroxypropylcellulose, hydroxyethylcellulose and / or methylhydroxypropylcellulose in an amount of 6-20 wt., are assigned to the solution or suspension, and optionally to a filler. an amount of 0-30 wt., attributed to the solution or suspension, optionally homogenizes and extracts the solution and the solution, respectively. the suspension in a foil extractor to a coating having a layer thickness, determined on the dry film, of 0.05-1 mm, preferably 0.07-0.3 mm, and dividing the film obtained upon drying the section into sections (dosage units) .
Fillers and active substances can be added to the foil formers and preferably a small amount of a release agent.
Suitable release agents include: polyoxyethylene polyoxypropylene polymers (PLURONIC F 68®, polyoxyl stearate, alkyl and acyl substituted ethylene oxide polyaddition products such as CREMOPHOR EL®, silicones and silicone release emulsions, glycerol, propylene glycol and metal soaps.
As fillers, cellulose, sugars, e.g. lactose, dextrose, cane sugar, etc., starches, polyhydric alcohols, e.g. mannite, calcium carbonate, calcium phosphate, talc and dyes in soluble
7507659-6 form or as pigment. The fillers can be partially or completely replaced with active substance. When using soluble fillers or active substances, a transparent, uniform film is formed, and when using insoluble fillers and active substances, a white or colored paper-like film is formed.
All active substances used in human and veterinary medicine can be introduced according to the invention. For internal use, especially oral administration is required. For topical use, in particular, is meant topical administration on the skin and in body cavities, e.g. nose, ear, vagina etc.
For example, active substances are: progestogens, estrogens, mixtures of progestogens and estrogens, tranquilizers, antidiabetic agents, sulphonamides, antibiotics, tricomonads, anti-inflammatory agents, e.g. corticoids etc.
The active drug substance may be dissolved in the carrier or be homogeneously suspended therein. The proportion of active substance in the foil can be about 0-60 1>. As unit dose (unit) pieces are punched or perforated containing the active substance amount, as is usually found in tablets, dragees, ointments, suppositories etc. Thus, depending on the type of use, the amount of active ingredient per single dose may be arbitrarily high or range from about 1 microgram to .0.5 grams, with the lower and upper dosage being easily under- or over-rated. Of course, carriers can also produce inert substance (placebo).
The solvent or suspension, which is present in about 48-81% (w / w), consists of water and / or one or more organic solvents. As organic solvents, physiologically acceptable solvents or solvents are provided which, upon drying, can be removed with only one physiologically hazard-free residue.
Such solvents are, for example, ethyl alcohol, isopropanol, methylene chloride, etc. and mixtures thereof. It is preferred to use water and ethyl alcohol or mixtures of water and ethyl alcohol.
The layer thickness of the wet smear is about 0.1-2 mm and the thickness of the dried film is about 0.05-1 mm, preferably 0.07-0.3 mm.
The method of preparing medicament in foil form in a continuous process, offers the advantage that the active substance is homogeneous and evenly distributed in the carrier for the active substance. The single dose can be varied in a very simple way by the concentration of active substance in the carrier, the thickness of the foil and the surface of the foil.
7507659-6
It is also possible to produce films with a smear in which different active substances and / or different concentrations of active substance are incorporated over the width of the foil band. With the aid of a special blade, consisting of two or more chambers, various solutions or suspensions can be drawn out without a premix to a continuous smear. The width and thickness of the smear can be set separately for each chamber. If desired, zones (strips) with different active substances or different concentrations can be observed through different dyes. A film is obtained by drying the wet smear, which at the corresponding partition, e.g. by perforation, provides units with various active substances and / or concentrations of active substance or units without active substance. Foils with various active substances and / or different concentrations of active substance are used for the preparation of multiphase preparations, for example for the preparation of. preparations for preventing conception. By the possibility of separating in the room of mutually incompatible active substances in a foil unit, the stability of the individual active substances is improved. Foils for intravaginal administration, for example, can also be rolled on a commercially available tampon.
The exemplary formulations, with the exception of Examples 5 and 16, are preferably suitable for oral administration.
Example 1
Production of 1000 units.
0.25 g of D-norgestrel
0.05 g of ethinyl estradiol and
0.84 g of polyoxyethylene polyoxypropylene polymer is dissolved with stirring i
95.00 g of ethyl alcohol and in this solution are added a powder mixture of lye, 93 g of hydroxypropyl cellulose and 16.93 g of cellulose.
The resulting suspension is withdrawn in a suitable foil draw device to a coat of one layer thickness of 500 µm and then dried.
Composition of a unit:
0j25 mg of D-norgéstrel
0.05 mg of ethinyl estradiol
0.84 mg of polyoxyethylene polyoxypropylene polymer
7507659-6
16.93 mg of hydroxypropyl cellulose
16.93 mg of cellulose
35.00 mg.
One unit corresponds to a surface of about 3 cm ^. The appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm. Example 2
Production of 1000 units.
1.10 g of Oremophor EL is dissolved in 152.00 g of water and in this solution is suspended and possibly homogenized
0.25 g of micronized D-norgestrel and
0.05 g of micronized ethinyl estradiol and introduced into the suspension
22.10 g of hydroxypropyl cellulose and 16.50 g of cellulose.
The slurry formed suspension is drawn into a suitable foil draw device to a coat with a layer thickness of 500 µm and then dried.
Composition of a unit;
0.25 mg of D-norgestrel
0.05 mg of ethinyl estradiol
1 + 10 mg Oremophor EL
22.10 mg of hydroxypropyl cellulose
16.50 mg of cellulose
40.00 mg.
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm. Example 5
Production of 1000 units.
0.03 g of D-norway
0.84 g of polyoxyl-40-stearate is dissolved by stirring in 95.00 g of ethyl alcohol and in this solution is added a powder mixture of
16.93 g of hydroxypropyl cellulose and
17.20 g of cellulose.
The resulting suspension is withdrawn in a suitable foil draw device to an irradiation with a layer thickness of 500 / ore and then dried.
7507659-6
Composition of a unit:
0.03 mg of D-norgestrel
0.84 mg of polyoxyl-40 starch
16.93 mg of hydroxypropyl cellulose
17.20 mg of cellulose
35.00 mg.
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm. Example 4
Production of 1000 units.
1.10 g of polyoxyethylene polyoxypropylene polymer is dissolved in 152.00 g of demineralized water and in this solution their suspension and possibly homogenisero are suspended. "
.. 0.03 6 micronized D-norgcstrel and into the suspension. passed
22.10 g of hydroxypropyl cellulose and 16.77 g of cdlulose.
The resulting suspension is withdrawn in a suitable foil-drawing device to a layer having a layer thickness of 500 µm and then dried.
Composition of a unit:
0.03 mg L-norgestrel
1.10 mg polyoxyethylene polyoxypropylene polymer
22.10 mg of hydroxypropyl cellulose 16.77 mg of cellulose
40.00 mg.
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of cs 170yUia. Example 5
Production of 1000 units.
0.025 g of fluocortolone trimethyl acetate and
0.183 g of glycerol is dissolved in 30,000 g of ethyl alcohol and introduced into this solution
7.292 g of hydroxypropyl cellulose.
The resulting solution is extracted in a suitable foil draw device to an ironing having a layer thickness of 500 µm and then dried.
7507659-6
Composition of a unit:
0.025 mg of fluocortolone trimethyl acetate
0.183 mg of glycerol
7, 292 mg of hydroxypropyl cellulose
7,500 mg.
ο
One unit corresponds to a surface of about 1 cm. Appearance of the foil: transparent. The dry film has a thickness of about 70 µm. The foil is suitable for topical use.
Example 6
Production of 1000 units.
10.00 g of 7-chloro-2-methylamino-5-phenyl-3H-1,4-hensodiazepine-4-oxide and
0.84 g of polyoxyethylene polyoxypropylene polymer is dissolved in 95.00 g of ethyl alcohol and in this solution a powder mixture of
16.93 g of hydroxypropyl cellulose and
7.23 g of cellulose.
The resulting suspension is withdrawn in a suitable foil draw device to an ironing having a layer thickness of 500 µm and then dried.
Composition of a unit:
10.00 mg of 7-chloro-2-methylamino-5-phenyl-3H-1,<sup>in</sup>in hensodiazepin-4-oxide
0.84 mg of polyoxyethylene polyoxypropylene polymer
16.93 mg of hydroxypropyl cellulose
7.23 mg of cellulose 35.00 mg.
One unit corresponds to a surface of about 3 cm. The appearance of the Eolx: yellow, paper-like. The dry film has a thickness of about 170 µm. Example 7
Production of 1000 units.
1.00 g norethisterone acetate0.03 g ethinyl estradiol and
0.84 g of polyoxyethylene polyoxypropylene polymer is dissolved in 95.00 g of ethyl alcohol and in this solution a powder mixture of
16.95 g of hydroxypropyl cellulose and
16.20 g of cellulose.
7507659-6
The resulting suspension is withdrawn in a suitable foil draw device to a coat having a layer thickness of 500 µm and then dried.
Composition of a unit:
1.00 mg norethisterone acetate
0.05 mg of ethinyl estradiol
0.84 mg of polyoxyethylene polyoxypropylene polymer
16.93 mg of hydroxypropyl cellulose
16.20 mg of cellulose
35.00. mg.
O
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm. Example 8
Production of 1000 units.
1.00 g norethisterone acetate
0.03 g of ethinyl estradiol and
0.84 g of propylene glycol is dissolved in a mixture of 101.60 g of methylene chloride and
26.40 g of ethyl alcohol and in this solution a powder mixture of
8.47 g of hydroxypropyl cellulose
8.47 g of hydroxyethyl cellulose and
16.19 g of cellulose.
The resulting suspension is withdrawn in a suitable foil draw device to a coat with a layer thickness of 500 µm and then dried.
Composition of a unit:
<td>1.00 mg</td><td>norethisterone</td>
<td>0.03 mg</td><td>ethinyl estradiol</td>
<td>0.84 mg</td><td>propylene glycol</td>
<td>8.47 mg</td><td>hydroxypropylcellulose</td>
<td>8.47 mg</td><td>hydroxyethylcellulose</td>
<td>16.19 mg</td><td>cellulose</td>
35.00 mg *
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm. Example 9
Production of 1000 units:
1.00 g norethisterone acetate
0.03 g of ethinyl estradiol and
7507659-6
.......
0.84 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
101.60 g of methylene chloride and
25.40 g of ethyl alcohol and in this solution a powder mixture of
16.93 g of hydroxyethyl cellulose and
16.20 g of starch.
The resulting suspension is withdrawn in a suitable foil draw device to an ironing having a layer thickness of 500 µm and then dried.
Composition of a unit:
1.00 mg norethisterone acetate
0.03 mg ethinyl estradiol
0.84 mg of polyoxyethylene polyoxypropylene polymer
16.93 mg of hydroxyethyl cellulose as well
16.20 mg of starch
35.00 mg.
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm. Example 10
Production of 1000 units.
1.00 g norethisterone acetate
0.03 g of ethinyl estradiol and
0.84 g of polyoxyl-40 stearate is dissolved in 95.00 g of ethyl alcohol and in this solution a powder mixture of
15.93 g of hydroxypropyl cellulose
8.10 g of lactose also
8.10 g corn starch.
The resulting suspension is withdrawn in a suitable foil drawstring to a coat having a layer thickness of 500 µm and then dried.
Composition of a unit:
1.00 mg norethisterone acetate
0.03 mg ethinyl estradiol
0.84 mg of polyoxyl-40 stearate
16.93 mg of hydroxypropyl cellulose
8.10 mg of lactose
8.10 mg corn starch
35.00 mg
7507659-6
One unit corresponds to a surface of about 3 cm. The appearance of the foil; white, paper-like. The dry film has a thickness of about 170 µm. Example 11
Production of 1000 units.
1.00 g of norethisterone (17α-ethinyl-19-nortestosterone)
0.03 g of ethinyl estradiol and
0.22 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
84.75 g of ethyl alcohol and
4.00 g of water and in this solution a powder mixture of is introduced and optionally homogenized
16.00 g of hydroxypropyl cellulose and 16.00 g of cellulose.
The resulting suspension is extracted into a suitable foil draw device to a smear with a layer thickness of 600 µm and dried.
Composition of a unit:
1.00 mg 0.03 mg 0.22 mg 16.00 mg 16.00 mg 33.25 mg.
norethisterone (I7a-ethinyl-19-nortestosterone) ethinyl estradiol polyoxyethylene polyoxypropylene polymer hydroxypropyl cellulose and cellulose
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 230 µm. Example 12
Production of 1000 units.
4.0 g of glyoxide (4-J 4 - [(5-methyl-isoxazole-3-carboxamido) -ethyl-benzolsulfony] -1,1-hexamethylene-semicarbazide) in micronized form are dissolved in
0.9 g of polyoxyl-40 stearate and is suspended and optionally homogenized
152.0 g of water and 15.0 g of hydroxyethyl cellulose and 15.1 g of calcium carbonate are added to the suspension.
The device for cash.
the suspension formed is drawn into a suitable foil-coated smear with a layer thickness of 5θθy ™ and tor7507659-6
Composition of a unit: 4.00 mg of glyoxide 0.90 mg of polyoxyl-40 stearate 15.00 mg of hydroxyethyl cellulose
15.10 mg of calcium carbonate
35.00 mg.
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm. Example 13
Production of 1000 units.
0.030 g of D-norgestrel is dissolved in
40,000 g of methylene chloride and
55,000 g of ethanol and in this solution are introduced and optionally homogenized
0.840 g of silicone oil.
6,930 g. methylcellulose
10,000 g of poly-N-vinylpyrrolidone and
17,200 g of starch.
The resulting suspension is withdrawn in a suitable foil draw device to a coat with a layer thickness of 500 µm and dried.
Composition of a unit:
0.030 mg D-norgestrel 0.840 mg silicone oil 6.930 mg methyl cellulose
10,000 mg of poly-N-vinylpyrrolidone
17,200 mg of starch
35,000 mg.
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm Example 14
Production of 1000 units.
0.84 g of polyoxyethylene polyoxypropylene polymer is dissolved with stirring i
95.00 g of ethyl alcohol and in this solution a powder mixture of
17.08 g of hydroxypropyl cellulose and 17.08 g of cellulose.
The resulting suspension is withdrawn in a suitable foil draw device to an ironing having a layer thickness of 500 µm and then dried.
Composition of a unit:
0.84 mg of polyoxyethylene polyoxypropylene polymer
17.08 mg of hydroxypropyl cellulose 17.08 mg of cellulose
35.00 mg.
Example 15
Production of 1000 units.
0.04 g of saccharin
0.04 g of cream essence as well
0.40 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
79.00 g of ethyl alcohol also
4.00 g of water and in this solution are introduced and optionally homogenized> 0.00 g of iron (II) fumarate 15.00 g of hydroxypropyl cellulose 5.52 g of cocoa and
4.00 g of cellulose.
The resulting suspension is withdrawn in a suitable foil-drawing device for one-coat ironing with a layer thickness of 0.5 mm and then dried.
Composition of a unit:
50.00 mg iron (H) fumarate. 15.00 mg hydroxypropyl cellulose
4.00 mg of cellulose
0.4Q mg of polyoxyethylene polyoxypropylene polymer.
5.52 mg of cocoa
0.04 mg of saccharin
0.04 mg cream essence
55.00 mg by weight per unit.
One unit corresponds to an area of about 3 cm 2. Appearance of the foil: light reddish brown.
Example 16
Foils for intravaginal administration.
The films are prepared according to Example 11.
Composition of a unit:
7507659-6
Γ
100.0 mg of 5-morpholinomethyl-3- (5-nitro-1-methyl-2-imidazolyl) -methyleneamino-2-oxazolidinone. HCl
8.4 mg Cremophor EL 169.2 mg methyl hydroxypropyl cellulose
72.4 mg of cellulose
350.0 mg by weight per unit.
One unit corresponds to an area of about 8 x 4 cm. Appearance of the foil: light yellow. The foil (1 unit) is either rolled on a commercially available tampon or rolled individually into a narrow tube.
Example 17
Two aspects are that.
Part 1:21 units with active substance.
Part 2: 7 units without active substance.
Preparation of 3000 units of part 1.
0.75 g of D-norgestrel
0.15 g of ethinyl estradiol and
0.54 g polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
237.00 g of ethyl alcohol also
12.00 g of water and in this solution are introduced and optionally homogenized
44.28 g of hydroxypropyl cellulose and 44.28 g of cellulose.
Preparation of 1000 units of part 2.
0.18 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of 79.00 g of ethyl alcohol and
4.00 g of water and in this solution are introduced and possibly homogenized
14.91 g of hydroxypropyl cellulose and 14-, 91 g of cellulose.
The thus-formed suspensions are drawn into a suitable foil draw device with a two-chamber special rake (the width of the chambers:
5<sup>Z |</sup> nimj 2-18 mm) to a smear of a thickness of 0.5 mm and then dried. When correspondingly divided into units of 18 x 18 mm, for example by perforation, three units can be divided into the width of the foil with one active substance and one unit with no active substance. You can now arbitrarily produce many sections with a ratio of three units with active substance and one unit without active substance.
7507659-6 - - Γ
Composition of a unit:
Part 1 (with active substance) Part 2 (without active substance)
<td>0.25 mg 0.05 mg 14.76 mg</td><td>D-norgestrel ethinyl estradiol hydroxypropyl cellulose sa</td><td>14.91 mg</td>
<td>14.76 mg</td><td>cellulose</td><td>14.91 mg</td>
<td>0.18 mg</td><td>polyoxietylenpolyoxipro- pylenpolymer</td><td>0.18 mg</td>
<td>30.00 mg</td><td>in weight per unit</td><td>30.00 mg</td>
<td>Area per unit</td><td>2 : about 3 cm. Appearance; White.</td><td></td>
Example 18
Three-phase preparation (two-stage preparation with active substance)
Part 1: 11 units of 0.05 mg D-norgestrel and
0.05 mg of ethinyl estradiol
Part 2: 10 units with 0.125 mg of D-norgestrel and 0.050 mg of ethinyl estradiol.
Part 5 '7 units without active substance.
Preparation of 1100 units of part 1.
0.055 g of D-norgestrel 0.055 g of ethinyl estradiol and
0.198 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
86,900 g of ethyl alcohol and
4,400 g of water and in this solution are introduced and optionally homogenized
16,346 g of hydroxypropyl cellulose and
16,346 g of cellulose.
Preparation of 1000 units of part 2.
0.125 g of D-norgestrel
0.050 g of ethinyl estradiol and
0.180 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
79,000 g of ethyl alcohol also
4,000 g of water and in this solution are introduced and possibly homogenized
14.823 g of hydroxypropyl cellulose and
14,822 g of cellulose.
7507659-6
Preparation of 700 units of part 3.
0.189 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
82.95θ g of ethyl alcohol and
4,200 g of water and in this solution are introduced and possibly homogenized
15.656 g of hydroxypropyl cellulose and
15.655 g of cellulose.
The suspensions thus formed are drawn into a suitable foil draw device with a three-chamber special blade (chamber width:
mm) to a smear and dried. In the corresponding division, for example by perforation, into units of 18 x 18 mm for part 1, 18 x 19.8 mm for part 2 and 18 x 28 mm for part 3, three units with different levels of active substance can be separated . The foil band can be separated with 11 units of part 1, 10 units of part 2 and 7 units of part 3 ·
<td rowspan="2">Part 1</td><td colspan="2">Composition of a unit:</td><td rowspan="2">Ingredient</td>
<td>Part 2</td><td>Part 3</td>
<td>0.050 mg</td><td>0.125 mg</td><td> -</td><td>D-norgestrel</td>
<td>0.050 mg</td><td>0.050 mg</td><td> -</td><td>ethinyl estradiol</td>
<td>0.180 mg</td><td>0.180 mg</td><td>0.270 mg</td><td>polyoxyethylene-polyoxypropylene polymer</td>
<td>14,860 mg</td><td>14.823 mg</td><td>22.366 mg</td><td>hydroxypropylcellulose</td>
<td>14,860 mg</td><td>14.822 mg</td><td>22.364 mg</td><td>cellulose</td>
<td>30,000 mg</td><td>30,000 mg</td><td>45,000 mg</td><td>weight per unit</td>
<td>then 3 cm<sup>2</sup></td><td>about 3.5 cm<sup>2</sup></td><td>about 5 cm<sup>2</sup></td><td>area per unit</td>
<td>White</td><td>White</td><td>White</td><td>• appearance</td>
<td>Example 19</td><td></td><td></td><td></td>
Trefaspreparat.
Part 1: 11 units with 0.05 mg of D-norgestrel and 0.05 µg of ethinyl estradiol
Part 2: 10 units with 0.125 mg of D-norgestrel and 0.050 mg of ethinyl estradiol
Part 3: 7 units with 50.00 mg iron (II) fumarate.
7507659-6
Preparation of 1100 units of part 1.
0.066 g of food gel no. 2 (Tartrazine; E 102) is dissolved in
4,400 g of water and then introduced into
86,900 g of ethyl alcohol are dissolved in this solution
0.055 g of D-norgestrel θ, θ55 g of ethinyl estradiol and
0.198 g of polyoxyethylene polyoxypropylene polymer and in this solution are introduced and optionally homogenized
16,313 g of hydroxypropyl cellulose and
16.315 g of cellulose.
Production of 1000 units over part 2.
0.065 g Food Orange No. 2 (Sunset Yellow; E 110) is solved in
4,000 g of water and then introduced into
79,000 g of ethyl alcohol and dissolved in this solution
0.125 g of D-norgestrel
0.050 g of ethinyl estradiol and
0.180 g of polyoxyethylene polyoxypropylene polymer and in this solution are introduced and optionally homogenized
14.790 g of hydroxypropyl cellulose and
14.790 g of cellulose.
Preparation of 7θ0 units of part 3 ·
0.042 g of saccharin
0.042 g of cream essence as well
0.406 g of polyoxyethylene polyoxypropylene polymer is dissolved in a mixture of
55,300 g of ethyl alcohol and
2,800 g of water and in this solution are introduced and optionally homogenized
35,000 g of iron (II) fumarate 17.5θθ g of hydroxypropyl cellulose
5,950 g of cocoa as well
4.060 g of cellulose
The suspensions thus formed are drawn into a suitable foil draw device with a three-chamber special blade (chamber width:
mm) to a smear and then dried. At the corresponding (division, for example by perforation, to units of 18 x 18 mm for part 1, 18 x 19.8 mm for part 2 and 18 x 28 mm for part 3, three units with different levels of effective can be divided on the width of the foil The foil band can be separated with 11 units of part 1, 10 units of part 2 and 7 units of part 3 ·
7507659-6
<td rowspan="2">Part 1</td><td colspan="2">Composition of a unit:</td><td rowspan="2">Ingredient</td>
<td>Part 2</td><td>Part 3</td>
<td>0.050 mg</td><td>0.125 mg</td><td> -</td><td>D-norgestrel</td>
<td>0.050 mg</td><td>0.050 mg</td><td> -</td><td>ethinyl estradiol</td>
<td> -</td><td> -</td><td>50,000 mg</td><td>iron (II) fumarate</td>
<td>0.180 mg</td><td>0.180 mg</td><td>0.500 mg</td><td>polyoxyethylene polyoxypropylene polymer</td>
<td>0.060 mg</td><td> -</td><td> -</td><td>Food Gel # 2</td>
<td></td><td>0.065 mg</td><td> -</td><td>Food Orange # 2</td>
<td>14,830 mg</td><td>14.790 mg</td><td>25,000 mg</td><td>hydroxypropylcellulose</td>
<td>14,830 mg</td><td>14.790 mg</td><td>5,800 mg</td><td>cellulose</td>
<td> -</td><td> -</td><td>8,500 mg</td><td>cocoa</td>
<td> -</td><td> -</td><td>0.060 mg</td><td>saccharin</td>
<td> -</td><td> -</td><td>0.060 mg</td><td>of cream essence</td>
<td>30,000 mg</td><td>30,000 mg</td><td>90,000 mg</td><td>weight per unit</td>
<td>p about 3 cm</td><td>z C 2 about 3.5 cm</td><td>about 5 cm</td><td>area per unit</td>
<td>yellow</td><td>Orange</td><td>brown</td><td>appearance</td>
Example 20
Production of 1000 units.
0.15 g of D-norgestrel
0.03 g of ethinyl estradiol and
0.84 g of polyoxyethylene polyoxypropylene polymer is dissolved. stirring i
95.00 g of ethyl alcohol and in this solution a powder mixture of
16.99 g of hydroxypropyl cellulose and
16.99 g of cellulose.
The slurry formed suspension is drawn into a suitable foil draw device to an irradiation having a layer thickness of 500 µm and then dried.
Composition of a unit:
0.15 mg of D-norgestrel
0.03 mg ethinyl estradiol
0.84 mg of polyoxyethylene polyoxypropylene polymer
16.99 mg of hydroxypropyl cellulose
16.99 mg cellulose / 5.00 mg
7507659-6
One unit corresponds to a surface of about 3 cm. Appearance of the foil: white, paper-like. The dry film has a thickness of about 170 µm.
<td>Example 21</td><td>Production of 1000 units.</td>
<td>Solution A</td><td>1.5 g of D-norgestrel as well 0.3 g of ethinyl estradiol is dissolved in 477.7 g of alcohol.</td>
<td>Solution B</td><td>1.5 g of polyoxyethylene polyoxypropylene polymer is dissolved in 23.0 g of water.</td>
<td>Solution C</td><td>Solutions A and B are combined.</td>
<td>Suspension D</td><td>88.1 g of hydroxypropyl cellulose and 88.6 g of cellulose are easily mixed, poured through a 1.2 mm screen and introduced with stirring into the solution 0. The resulting suspension is withdrawn in a suitable foil draw device to a coat having a layer thickness of 600 µm and dried. Composition of a unit: 0.15 mg of D-norgestrel 0.03 mg ethinyl estradiol 8.81 mg of hydroxypropyl cellulose 8.86 mg of cellulose 0.15 mg polyoxyethylene polyoxypropyl enopolymer 18.00 mg</td>
P
One unit corresponds to a surface of about 144 mm. Appearance of the foil: white, paper-like. Thickness of the film: 260 - 280 µm.
j
7507659-6
Contents2
44 members in 27 offices
Priority claims8
| Document | Office | Kind | Date |
|---|---|---|---|
| 2432925 | Germany | A | |
| 2432925 | Germany | A | |
| 2449865 | Germany | A | |
| 2449865 | Germany | A | |
| 2432925 | – | – | – |
| 2449865 | – | – | – |
| DE19742432925 | – | – | – |
| DE19742449865 | – | – | – |
Members44
| Document | Office | Kind | |
|---|---|---|---|
| BE831024A | Belgium | A | |
| IE42604L | Ireland | L | |
| DK295075A | Denmark | A | |
| FI751801A | Finland | A | |
| NO752416L | Norway | L | |
| NL7507785A | Netherlands (Kingdom of the) | A | |
| SE7507659L | Sweden | L | |
| DE2432925A1 | Germany | A1 | |
| FR2276811A1 | France | A1 | |
| JPS5129218A | Japan | A | |
| DE2449865A1 | Germany | A1 | |
| ZA754305B | South Africa | B | |
| DD122196A5 | German Democratic Republic (until 1990) | A5 | |
| AU8252775A | Australia | A | |
| ES439159A1 | Spain | A1 | |
| IN142428B | India | B | |
| EG11756A | Egypt | A | |
| ATA513275A | Austria | A | |
| CS181182B2 | Czechoslovakia (until 1993) | B2 | |
| GB1510999A | United Kingdom | A | |
| IL47573A | Israel | A | |
| AT346492B | Austria | B | |
| US4136145A | United States of America | A | |
| US4136162A | United States of America | A | |
| HU173016B | Hungary | B | |
| PL101842B1 | Poland | B1 | |
| US4152159A | United States of America | A | |
| CA1067407A | Canada | A | |
| FR2276811B1 | France | B1 | |
| SE413285BThis record | Sweden | B | |
| RO68836A | Romania | A | |
| IE42604B1 | Ireland | B1 | |
| DE2432925B2 | Germany | B2 | |
| DE2449865B2 | Germany | B2 | |
| DK143221B | Denmark | B | |
| FI60354B | Finland | B | |
| CH625704A5 | Switzerland | A5 | |
| DK143221C | Denmark | C | |
| FI60354C | Finland | C | |
| JPS6028810B2 | Japan | B2 | |
| DE2432925C3 | Germany | C3 | |
| PH18973A | Philippines | A | |
| NL186294B | Netherlands (Kingdom of the) | B | |
| NL186294C | Netherlands (Kingdom of the) | C |
2 legal events, as the office reported them to INPADOC
Over the term
Point at a mark for the eventEvents
| Event | Code | |
|---|---|---|
| Patent has lapsedLapsedNUG | NUG | |
| Patent in forceNAL | NAL |
Numbers
- Publication, DOCDB
- 413285
- Publication, EPODOC
- SE413285
- Application
- 75076596
- Application, DOCDB
- 7507659
- Application, EPODOC
- SE19750007659
Titles2
- Swedish
- SAETT ATT FRAMSTAELLA EN LAEKEMEDELSBAERARE I FOLIEFORM MED INKORPORERAD VERKSAM SUBSTANS
- English
- PREPARED TO MANUFACTURE A PHARMACEUTICAL CARRIER IN FILM FORM WITH INCORPORATED ACTIVE SUBSTANCE
Classification
- CPC, 1
- A61K9/7007
- IPC, 2
- A61K31 57
- A61K9 70