Digestible and administrable primary package in the form of a film or wafer

The present invention relates to a method of making the primary packaging of a film or wafer administration form intended for oral administration. In particular, the invention relates to a method for producing a primary package consisting of a packaged film or wafer administration form, as well as a section of an upper and a lower strip of packaging material.

Drug forms for administration in the form of a film or wafer for oral administration are known, inter alia, from US 3 007 848, DE 24 32 925, DE 27 46 414 and EP 219 762. such as tablets or capsules, especially their geometric shape and method of preparation. Their common feature is a thin and flat shape, the differences in flexibility, brittleness, smoothness or consistency result in the form of the film or foil, or the resemblance to paper or wafer. In their production, it is recommended, especially in the industrial production of films, to use pressure extrusion and coating processes.

Depending on the purpose of application, two basic types of design are offered. One of these forms is rapidly disintegrating or rapidly releasing active ingredients, intended to disintegrate in the oral cavity immediately after administration, combined with the release of the active ingredient, the term "fast disintegrating according to the invention" to a disintegration time under the action of saliva ranging from from a few seconds to a maximum of a few minutes. The second type includes those which disintegrate slowly or practically do not disintegrate at all, which are suitable, above all, for slow or continuous release of the active ingredient, this type being adhered to the oral mucosa by the addition of substances sticking to the mucosa during the release of the active ingredient. Both basic drug types can be designed such that, depending on the active ingredient introduced, they are suitable for the local treatment of the oral mucosa or for the systemic administration of the active ingredient.

The packaging of these dosage forms for administration in the primary packaging is carried out not without problems by the usual methods for known pharmaceutical products such as capsules or tablets, by means of packaging means or machines. Primary packaging for a solid dosage form, developed taking into account a modern approach, should protect the product from external influences, and on the other hand, should allow for the conscious and controlled removal of individual dosage units, in order to allow for their intake at the desired time, while taking out should be in such a way that they will not be damaged.

While often glass packages or cans are filled with a large number of tablets and capsules, which hardly meets the above-mentioned requirements, more than once the dosage units are packed in blister packs or deep-drawn packs. Such primary packages contain a large number of dosage units, separately hermetically sealed in the void between two lengths of strips of packaging material. The void is created prior to filling by hot or cold forming the bottom strip of packaging material with a suitable tool. After filling the void, the upper strip of packaging material is sealed to the lower strip.

With modern blister packs, the removal of the dosage unit takes place such that a finger pressure is applied to the outside of the formed recesses in the lower strip of packaging material, and thus to the tablet or capsule, to break the upper strip of packaging material and eject the dosage unit. However, this is only possible if the strength of the packaging material used for the top strip does not exceed a certain value.

Although this primary packaging solution has found wide application with known administration forms, this solution has significant drawbacks in the case of film or wafer administration forms. Tests have shown that two of the drawbacks are particularly important, one related to the manufacture and the other to the removal of the dosage units from such primary packaging.

Oral film or wafer dosage forms - especially in the fast-releasing type - are generally much lighter and less compact than conventional tablets or capsules. The proposed dimensions of the dosage units for the drug in the form of a film or wafer are

About 1 cm² (e.g. DE 27 46 414) up to 3 cm² or more (e.g. DE 24 32 925) with a thickness of about 0.05 to 1 mm (e.g. DE 24 32 925). Accordingly, when using conventional pharmaceutical base materials, it achieves drug units weighing from about 5 to 100 mg, with typical and preferred embodiments being at the lower end of this range. The insertion of such thin films or wafers into vesicles has proved to be very difficult. Particularly in high-speed machines, the air movement caused by the moving parts of the machines, and often also the electrostatic charges of the packaging material, make the dosage units of the medicament not arrange properly into the vesicles or, once arranged, are blown away from the vesicles. While it is possible to manufacture deep drawn primary packages for oral films and wafers, it is an expensive and ineffective packaging solution due to the problems outlined.

Removal of the film or wafer form for administration from blister packs corresponding to the usual primary packets for tablets or capsules is also problematic. A flat dosage unit in a recess is difficult to squeeze through the material of the top pack strip as neither its format nor its mechanical strength are suitable for this purpose. The risk that the dosing unit will be damaged during the extrusion is relatively great. Even if one first tries to tear the material of the top pack strip in some other way, e.g. with a fingernail, it is not easy to grip and remove the flat dosage unit from the open cavity, unless very deep recesses are selected, which is disadvantageous for other reasons, such as as too large a volume of entrapped air, in relation to the low weight of the dosage form.

Additional difficulties arise in conventional confectioning if the film or wafer administration form is brittle and crumbles. In this case, while rigid blister packs may provide some protection for the product during storage, removal of the dosage units becomes even more difficult.

Despite these drawbacks of the known blister packs for film or wafer administration forms, the choice of suitable materials for such packs is limited. Besides, the available materials are not particularly cheap substances.

Several approaches to creating a primary package for a film or wafer dosage form without the disadvantages described are disclosed in US 3,007,848. The solutions presented therein are in part of interest to all film or wafer administration forms, although unlike the present invention, U.S. Patent 3,007,848 relates more narrowly to (1) wafers produced by extrusion or printing on edible films that (2) ) are intended to be swallowed, not for use in the mouth, and in addition (3) are optionally sealed into strips of an edible, smooth and easy-to-swallow foil. However, the subject of the cited description is the packaging of wafers by welding the dosage units between two films which in a general sense should be considered as packaging material. It further discloses "light welding of the dosage units for simplified opening of the recesses and removal of the wafers. It also describes a non-heated edge of the packaging material, which makes it easier to grasp the packaging films and separate them from each other to facilitate removal of the wafers.

Also, the solution disclosed in US 3 007 848 representing the related art does not meet all the requirements for appropriate primary packaging for a film or wafer form of administration. Some disadvantages and problems have remained unresolved or have only arisen with the proposed package design.

The packaging proposed there contains only one wafer at a time, while a semi-finished product can be provided which represents an undefined but very large number of packaged dosage units in the form of a so-called the rolled up tape. The primary packaging used in practice should, for various reasons, contain a clearly defined number of dosage units. Failure to comply with this requirement leads to serious shortcomings in the secondary packaging: first one has to collect separated small primary packages filled with a single wafer in accordance with US 3 007 848, deduct a package containing, for example, 20 of these packages and put them together, which is associated with a significant cost and leads to bulky secondary packaging. For subsequent use, the original package has to be removed, opened and the wafer each time, and it is very difficult to control the number of doses taken up to a certain point in time. For example, there is 50 wafers in the secondary packaging

PL 195 971B1 it is almost impossible to determine whether or not the correct dose has been taken, without laborious recalculation of the remaining wafers.

The object of the invention is therefore to provide a method for producing the primary packaging of a film or wafer administration form which meets all the above-mentioned requirements without showing the described drawbacks of the known solutions.

This object is achieved by a method of manufacturing a primary package for a film or wafer dosage form for oral administration with a section of an upper and a lower strip of packaging material. The method according to the invention is characterized in that the form for administration in the form of a film or wafer is prepared as a strip of a laminate with a carrier film, dosing units are punched out of this laminate, and then the dosing units are released from the film by shifting and changing the direction of travel of the cut laminate. and inserted between the strips of packaging material, the strips being sealed together in lengths to form dosing unit compartments.

Preferably, the laminate is removed from the roll-type supply by means of a roller or gripper drive, punched out and guided over an edge or a guide roller for the separation of the dosage units.

Moreover, the strips of packaging material are preferably guided over one another via a guide roller and at the same time the dosing units released from the carrier film are introduced between the two strips of packaging material.

Preferably, the primary packages are separated on a slitting or punching device in a later process step.

This method produces a plurality of film or wafer dosage units individually welded into flat, spaced apart compartments formed without cold or hot forming of the packaging material, and that there are perforations between the two compartments in if necessary, allowing separation in individual compartments.

The method according to the invention provides the desired, practically usable primary packaging. The solution known from the patent US 3 007 848 can only be changed in that the solution is obtained from a semi-finished product in the form of a coil or tape, by cutting it, but not - as required - after each wafer, but only more or less after each wafer. every tenth wafer. The packaging thus obtained contains a predetermined number of dosage units, but they cannot be removed easily and without problems. Tests have shown that when opening such a package to remove one dose of medicament, as a rule, a welded seam or a welded surface around several dosage units is torn, so that several of them are exposed at the same time and are no longer protected by the original package. After all, the intended removal of one single dosage unit by forcing it through the material of the original packaging is, after all, also impossible, as described above, due to the low mechanical strength of the dosage form with respect to the packaging material.

The primary package must have a perforation between the compartments which contain the dosage units, namely such a perforation which allows one single dosage unit to be withdrawn if necessary, first by separating the compartment with the dosage unit and then opening the compartment without damaging the other compartments. Moreover, the perforation has the advantage that, with an appropriate configuration with as few small retaining points as possible, it also allows the compartment to be opened without first separating it and without simultaneously opening other compartments.

A further advantage of this primary package is the relatively small gas-filled space in the compartments for the dosage units. With the right choice of primary packaging material, the products sensitive to oxidation and moisture can thus be largely protected against the harmful effects of oxygen and air moisture.

A further advantage of this primary packaging is the small amount of packaging material and the convenient, space-saving format. For example, a folding box 1 cm high can readily accommodate 10 or more primary packages of 10 dosage units.

A further advantage lies in the possibility of using a significantly thinner and less expensive material than the material used for the production of packaging as the bottom packaging strip.

It is blister-like and cold- or hot-shapable and must have a certain minimum thickness and lightest weight.

A further advantage of this primary packaging is that the treatment regimen can be made visible by printing it on the packaging. For example, packs in the form of weekly packs with 7 dosage units of once-a-day medication may be produced, with the individual compartments in the packet having printed names or abbreviations for the days of the week. Based on these printed treatment regimens, patients can easily monitor their intake. In a preferred embodiment, such a package is printed on.

Film or wafer administration forms, such as those described, for example, in DE 24 32 925, are particularly preferably first produced as cast films from which the dosage units can be obtained by cutting or punching. Consequently, another embodiment of the primary package comprises dosage units which are sections or cut shapes of cast film. Cast films in the sense of the invention include all film preparations which are produced by pouring a carrier material or coating it with polymer-containing solutions, suspensions or emulsions, followed by drying.

A further embodiment of the primary package includes a weld seam or a heat sealed surface between a section of the top strip of packaging material and a portion of the bottom strip of packaging material that are peelable from each other. Peel-off properties within the meaning of this invention include all welded seams or welded surfaces which, with a moderate peel force, e.g. less than about 10 N / 15 mm may be separated, with typically portions of packaging material remaining intact. For the production of such peelable welding seams, special welding materials are used, e.g. so-called "peel-PE, special polyethylene, usually containing another polymer such as polystyrene, and special welding conditions (pressure, time, temperature) are applied. However, it is also possible to weld conventional materials under these conditions, with the result that a joint is not formed in the form of a fused joint, but a peelable joint.

In another embodiment, the primary wrapping is provided with a non-welded edge beside each compartment in addition to the welded surface or welded seam on at least one side. It plays the role of a handle, allowing the sections of the upper and lower strips of packaging material to be easily grasped and separated by opening the compartment. In yet another form of the primary packaging, the relatively unheated edges in the sections of the upper and lower packaging material strips each have a different length. If only one of the two pieces of packaging material protrudes over the edge, it is particularly easy to grip and can be easily folded away from the other piece of packaging, whereby both sides of the packaging can be gripped more easily.

The strips of material for making such primary packages may be monolayer, but are generally multi-layered, which makes it possible to meet the requirements of modern packaging materials for film or wafer administration forms. Often used layers are e.g. kraft paper for stiffness, plastic films for tensile strength and tightness of the packaging material, sealing varnish for better welding, protective varnish for impregnating kraft paper, aluminum for particularly high tightness, adhesive for bonding individual layers, etc. For economic reasons, optimal packaging laminates do not contain more layers and are not thicker than is necessary for the particular purpose.

In certain cases, it is necessary to use a particular packaging laminate for the primary packages not only for the top stripe of the packaging material, but also for the bottom stripe. If, for example, a particular gas tightness is required, which can only be achieved with an aluminum insulating layer, such a layer is used in both packaging strips.

In other cases, however, different requirements may be imposed on the material for the upper and lower straps. Where the primary packaging is to have a specified minimum stiffness and for better handling in the primary packaging, a packaging strip with a flexural strength of at least x with an aggregate minimum thickness of y mm is used, it is sufficient if this stiffness is predominantly obtained from one strip of packaging material while the material used for the second packaging strip is optimal for other reasons, e.g. economic or technical.

PL 195 971B1

Another variant of primary packaging with two differently structured packaging strips comprises an upper strip of transparent packaging material through which the dosage units can be seen in the packaging without being damaged. The definition of the top and bottom strips is arbitrary. In the sense of the invention, when using one strip of transparent and the other opaque packaging material, the transparent strip is defined as the top strip. The advantage of this variant is the simple visual control of the dosing compartments or units and their condition. A further advantage is that an imprint on the upper side of the lower band or also on the dosage units is recognizable by the transparent upper band. Since such imprints, as already described, are advantageous, inter alia in terms of drug uptake control, a further variant of the primary packaging comprises a transparent section of an upper stripe of packaging material and either a bottom stripe with an imprint on its upper side or a dosage unit imprinted on the upper side. side.

Such packages are suitable for all known film or wafer administration forms. These include simple, single-layer preparations which usually disintegrate rapidly in saliva, as well as multi-layer systems that stick to the mucosa for a long time and release the active substance, the layers of these systems having correspondingly different compositions and at least one of these layers slowly or it does not break down at all in saliva, and another layer adheres to the mucosa.

The subject matter of the invention is illustrated by an embodiment in the drawing, in which Fig. 1 shows a method of producing packages for square or rectangular dosage units, Fig. 2 shows another multi-stage method of producing packages, and Fig. 3 shows a package obtained by a method according to the invention.

Such primary packages can surprisingly be efficiently machine-made. The method of producing packages for square or rectangular dosage units 5 shown in Fig. 1 consists of at least the following main process steps, supplemented if necessary by further steps of printing, additional packaging molding, etc. In a first step, the upper strip 1 and the lower strip 2 of packaging material, without cold or hot forming, are guided over each other by a guide roller 3, while at the same time the film or wafer form 4 is fed between the two packaging strips by means of a roller or tick drive 17. It is preferred that the application forms for administration in the form of a film or wafer as a strip, one or more strips parallelly spaced apart, are brought to the desired width of the dosage unit 5. It is also preferred that the diameter of the guide rollers is smaller than the length of the dosage units as measured in the direction of the belt movement. In a further step of the process, the dosing units 5 from the strip-shaped drug form are split on a cutting device 6 positioned directly in front of the guide rollers. In a further process step, the two strips of packaging material are welded together by means of a heated sealing tool 7 in such a way that the individual dosing units 5 are sealed in the compartment 8 and completely surrounded by the weld seam or the welding surface 9. In a further process step, a perforation is punched between the compartments 8 at the punching device 12. Then, the primary packages 11 can be separated at the second slitting or punching device.

The production method according to the invention is shown schematically in FIG. 2. In this case, the described process steps can be supplemented, if necessary. The manufacturing method comprises in one step preparing a laminate 13 from a film-like or wafer-shaped administration form 4 and a carrier foil 14, from which the dosage units 5 are punched out in a further step with a punching device 15 without simultaneously punching out the carrier foil 14. In a later process step, the cut laminate 13 is guided over the edge or guide roller 18 by means of a roller or gripper drive 17 that the dosing units 5 are released from the carrier film 14. If necessary, a scraper 16 can additionally be used. At a later stage in the process, the upper strip 1 and the lower strip 2 of packaging material, without cold or hot forming, are each brought on top of each other by means of a guide roller 3, at the same time the dosing units 5 released from the carrier film 14 are introduced between the two strips of packaging material 1i. 2. In a later process step, the two strips of packaging material are sealed to each other using a heated sealing tool 7 similar to that shown in Fig. 1 in such a way that the individual dosing units 5 are welded in the compartment 8 and completely surrounded by the weld seam or the welded surface 9. In a further step

In the process, a perforation is punched between the compartments 8 on the punch device 12. In a further step in the process, the primary packages 11 can be separated on the second cutting or punching device.