METHOD AND DEVICE FOR IMPRECIZING A FILM, AND METHOD FOR PRODUCING A TRANSDERMAL THERAPEUTIC SYSTEM

Description

[0001] The invention relates to a device system for producing a transdermal therapeutic system with a device for impregnating a film and a method for producing a transdermal therapeutic system.

[0002] Impregnated films, especially membranes, are used, for example, as a layer in transdermal therapeutic systems.

[0003] For example, US 4 436 741 A describes a transdermal therapeutic system for the delivery of scopolamine, which has an oil-impregnated membrane.

[0004] A common method for impregnating films, such as membranes, is coating on a coating system using reverse roll coating with an engraving wave.

[0005] When using engraving rollers, the amount of impregnation is determined by the engraving on the roller, e.g., the engraving gap. For any variations in the amount of impregnation, the roller, e.g., the engraving depth, must be changed.

[0006] One disadvantage of existing methods is that the film is not loaded with impregnating agent in an accurate manner.

[0007] Furthermore, existing methods are time-consuming, complex and / or require additional work steps and / or equipment from a production technology perspective.

[0008] Further prior art relating to the present invention is described in EP 2 844 202 A1 and US 4 902 565 A.

[0009] The object of the invention is to provide a method for impregnating a film, a device for impregnating a film and a method for producing a transdermal therapeutic system, wherein the impregnation is optimized.

[0010] According to the invention, the problems are solved by a method for producing a transdermal therapeutic system according to claim 1 and a device system for producing a transdermal therapeutic system according to claim 2.

[0011] The inventive method for producing a transdermal therapeutic system is, in particular, a method for producing a transdermal patch or a precursor for a transdermal patch. The method for producing a transdermal therapeutic system comprises the steps of the method for impregnating a film described below. It is preferred that the apparatus described below be used in carrying out the method for impregnating a film. The method for producing a transdermal therapeutic system further comprises the step of adding an active ingredient to and / or onto the impregnated film. It is possible that the film is coated with the active ingredient, which is particularly liquid.

[0012] Alternatively, or additionally, it is also possible for the impregnated film to be bonded to one or more films containing the active ingredient to form a film composite. The active ingredient is, in particular, scopolamine.

[0013] The method for impregnating a film, which is part of the inventive method for producing a transdermal therapeutic system, is in particular a method for impregnating a membrane, preferably for use in transdermal therapeutic systems. A first step of the method for impregnating a film consists of feeding the film to be impregnated. Preferably, the film is fed by a roll process, so that it is unwound from a feed roll. The fed film is immersed in an impregnating agent. In particular, the film is completely immersed in the impregnating agent. The impregnating agent is preferably arranged in an immersion tank, also to be referred to as an impregnation bath. In a preferred embodiment, the film is guided, at least partially, substantially horizontally through the impregnating agent.Preferably, the film is completely saturated with impregnating agent after passing through it. Subsequently, the impregnating agent is partially separated from the film. This separation is carried out in such a way as to achieve a predefined loading of the film with impregnating agent. Specifically, the separation results in a loading of the film with oil of 5 g / m² to 20 g / m², preferably 7 g / m² to 13 g / m², and most preferably approximately 10 g / m². Preferably, the separation is achieved by wiping the impregnating agent off the film.

[0014] The invention preferably further relates to a device system for producing a transdermal therapeutic system. The device system comprises a device for impregnating a film and an active ingredient delivery device. The active ingredient delivery device is arranged and / or configured for adding an active ingredient to and / or onto the impregnated film. It is possible that the film is coated with the active ingredient, in particular a liquid one. Alternatively, or additionally, it is also possible that the impregnated film is bonded to one or more films containing the active ingredient to form a film composite. The active ingredient is, in particular, scopolamine.

[0015] The device for impregnating a film, which is part of the device system according to the invention, is in particular a device for impregnating a membrane, preferably for use in transdermal therapeutic systems. The device has a dipping basin filled with impregnating agent, also to be referred to as an impregnation bath. The dipping basin is designed and / or arranged for, in particular, the immersion of the film into the impregnating agent. The device has a film guide. The film guide is designed in particular for feeding the film, for guiding the film through, for immersing the film in the dipping basin, and / or for expelling the film.Feeding the film means, in particular, guiding the film into the device; guiding the film within the device means, in particular, guiding the film; immersing the film means, in particular, guiding the film through the immersion tank; and ejecting the film means, in particular, guiding the film out of the device. It is preferred that at least one, in particular rotatable, deflection roller for guiding the film is arranged at least partially within the immersion tank. It is particularly preferred that at least two, in particular exactly two, deflection rollers are arranged within the immersion tank such that the film can be guided substantially horizontally, at least through a portion of the immersion tank. Furthermore, it is preferred that the film guide has at least one, in particular rotatable, roller, e.g., a deflection roller. The at least one roller is preferably round. It is preferred that at least one roller is driven.Preferably, the film guide has a feed roller for unwinding the film and / or an output roller for winding the film. At least one of the feed rollers and the output roller are preferably driven. The at least one roller, in particular the feed roller and / or output roller, can preferably be arranged outside, inside, or partially outside and inside the device. The device also has a separating device for, in particular partially, separating the impregnating agent from the film. The separating device is preferably designed such that the impregnating agent is separated to achieve a predefined loading of the film with impregnating agent.

[0016] In the method according to the invention, it is preferred that the impregnating agent is separated by means of a separating device. The separating device used in the method is, in particular, designed like the separating device of the device according to the invention.

[0017] In a preferred embodiment, the separating device comprises at least one scraper. The scraper preferably has a silicone coating. In particular, the scraper is coated, or more preferably bonded, with a silicone film preferably 0.8 mm to 3 mm thick. It is preferred that the scraper is designed and / or arranged such that it comes into contact with the film loaded with impregnating agent, preferably being pressed against it. The scraper is particularly subjected to pressure. It is preferred that the separating device removes the impregnating agent from one side of the film or from both sides of the film.

[0018] In a preferred embodiment, the cutting device has at least one edge and / or at least one, preferably rotatable, roller. The edge preferably has an angular or rounded structure. It is preferred that the edge is designed and / or arranged such that it comes into contact with the film as it enters or exits the edge. In other words, it is preferred that the edge has an acute, obtuse, or right-angled angle to the film with respect to the film's direction of travel. It is preferred that the cutting device has at least one pressure plate that forms the edge. The pressure plate is particularly flexible.

[0019] In a preferred embodiment, the scraper is arranged on both sides of the film loaded with impregnating agent.

[0020] In a preferred embodiment, the wiper comes into contact with the film on both sides, particularly by pressing down on it. It is preferred that the at least one wiper in the double-sided embodiment has two opposing rollers. Alternatively, the double-sided wiper can have two opposing edges, or one edge and an opposing pressure surface, e.g., of an anvil.

[0021] In a preferred embodiment, the separating device, in particular the at least one scraper, is variably adjustable so that the predefined loading of the film with impregnating agent can be achieved by separating the impregnating agent. It is therefore preferred that the separating device, in particular the at least one scraper, is designed such that a desired loading, e.g., a predefined quantity of oil in liters or kilograms per square meter of film area, can be achieved.

[0022] In a preferred embodiment, the separating device for setting the predefined load comprises at least one adjusting device. The adjusting device particularly comprises, or consists of, one of the following: a pneumatic device, a hydraulic device, a spring device, an elastomer, a pressure screw, and a fine adjustment thread. This adjusting device is particularly arranged and / or designed to adjust the pressure with which the at least one scraper presses against the film and / or the distance between the at least one scraper and the film. In a double-sided embodiment of the at least one scraper, the adjusting device is particularly arranged and / or designed to adjust the pressure and / or distance between the two opposing elements, e.g., rollers, edges, or contact surfaces, of the scraper.

[0023] The spring device comprises, in particular, a compression or tension spring, especially a coil spring. The elastomer, which is primarily rubber, is in particular an elastic band. Preferably, the angle of attack of the scraper, especially in a version with an edge, is adjustable. For example, it is preferably implemented that the angle of the edge, e.g., of the pressure plate, is variable relative to an opposite edge or to an opposite contact surface. The adjustability of the scraper allows, in particular, the adjustment of different loading conditions. It is preferably possible that, in the case of a double-sided scraper, the opposing elements are offset or parallel to each other. It is also preferred that the offset of the opposing elements is adjustable.

[0024] It is preferred that the separating device has one or more of the scrapers described above, in particular in different designs.

[0025] In a preferred embodiment, the separating device is, at least partially, designed and / or arranged such that the separated impregnating agent is returned to the immersion tank. Preferably, the separating device is, at least partially, designed and / or arranged such that the separated impregnating agent falls into the immersion tank due to gravity. It is preferred that the separating device is, at least partially, arranged above the immersion tank. The method according to the invention includes, in particular in addition to or as an alternative to this embodiment of the separating device, the step of returning, preferably by gravity, at least parts of the separated impregnating agent. It is preferred that the film is guided substantially vertically after leaving the immersion tank, e.g., by the film guide.

[0026] In a preferred embodiment, the device includes a collection tray, preferably connected to the immersion tank, for collecting the separated impregnating agent. The collection tray is preferably connected to the immersion tank via a fluid-carrying connection. Alternatively, it is preferred that the collection tray be separate from the immersion tank. It is also preferred that the collection tray be larger, particularly in surface area, than the immersion tank. Preferably, the immersion tank and the collection tray cover, and in particular completely cover, the area below the separation device, so that separated impregnating agent, e.g., dripping down, is collected.

[0027] In the preferred formulation, the impregnating agent is oil, in particular mineral oil. The impregnating agent is especially skin-friendly.

[0028] In a preferred embodiment, the film comprises polypropylene, and in particular consists of polypropylene. The film is preferably porous, and ideally microporous. The film is, in particular, Celgard® < 2400 from the company Celgard.

[0029] In a preferred embodiment, the method according to the invention comprises the further step of performing an inspection, in particular process control, of the film loaded with impregnating agent. This step is performed, in particular, after the impregnating agent has been separated to achieve the desired loading. The inspection specifically involves determining the existing loading. This existing loading corresponds, in particular, to the actual loading. Preferably, the actual loading is also compared with a target loading. It is also preferred that the step of adjusting the separating device, in particular to adapt the actual loading to the target loading, is performed. The inspection is performed, in particular, by optical and / or weight detection. It is preferred that a portion of the film is removed for inspection, e.g., cut out, and then this portion is tested. The inspection can preferably be carried out with the inspection device described below.

[0030] In a preferred embodiment, the device includes a test device for inspecting the film loaded with impregnating agent. The test device is arranged, in particular, downstream of the cutting device in the film guidance direction. The test device preferably includes a scale for weighing the film. Additionally or alternatively, the test device includes, in particular, at least one optical inspection device, such as a camera. The test device can also be designed, for example, to be magnetic or electrical, so that, for example, the conductivity of the film can be measured.

[0031] A particularly important, and especially final, step in the process for impregnating a film preferably consists of drawing the impregnated film. This drawing is preferably carried out using a rolling process, such that the impregnated film, or a film composite containing the impregnated film, is wound onto a drawing roll. The feed roll and / or the drawing roll may preferably be driven.

[0032] In particular, the features described in the context of the process for impregnating a film are also applicable to the device, and vice versa. The process for manufacturing a transdermal therapeutic system is preferably carried out using a device as described above.

[0033] The process for manufacturing a transdermal therapeutic system is, in particular, a continuous process.

[0034] In the context of this application, "impregnated" refers in particular to the loading of a film, especially a porous one, with an impregnating agent, such as oil.

[0035] A further advantage of the invention is that the impregnation step, particularly when using the film in transdermal therapeutic systems, can take place within a manufacturing plant or during manufacturing, instead of as an additional coating step or within a coating plant as previously done in the prior art.

[0036] The invention will now be explained in more detail with reference to preferred embodiments and the accompanying drawings.

[0037] They show: Fig. 1 a schematic side view of an embodiment of the device according to the invention, Figs. 2a-2c schematic representations of alternative wipers based on detail section II from Fig. 1, and Fig. 3 a perspective side view of a further embodiment of the device according to the invention.

[0038] Similar or identical components or elements are identified in the figures by the same reference symbols or variations thereof (e.g. 12 and 12', 12" or 14 and 14', 14").

[0039] Figure 1 shows an embodiment of a device 10 according to the invention for impregnating a film 12.

[0040] The film 12, preferably porous, is unwound from a feed roller 36, the feed roller 36 rotating counterclockwise, as shown by arrow 58. The film 12 is thus guided in the direction of arrow 40.

[0041] The film 12 not yet loaded with impregnating agent 14 is identified by reference numeral 12', while the loaded film 12 has reference numeral 12".

[0042] The film 12' is first guided into a dipping tank 16 filled with impregnating agent 14 and there, preferably completely, loaded with impregnating agent 14. Inside the dipping tank 16, two deflection rollers 34 are arranged such that the film 12 runs substantially horizontally through the impregnating agent 14 in the dipping tank 16. The loaded film 12" then exits the dipping tank 16.

[0043] The film 12" is then guided into a first scraper 20b of a separating device 18. Here, the film 12" is pressed by the pressure plate 26 with edge 27 against the pressure surface 28 (indicated by arrow 29). This separates portions of the impregnating agent 14 from the film 12". This is illustrated by the droplet 14' of removed impregnating agent 14. Due to the arrangement of the scraper 20b relative to the dipping tank 16, the removed impregnating agent 14 falls back into the dipping tank 16 and can be reused.

[0044] The film 12" is guided via the deflection roller 34 into a further scraper 20a of the separating device 18. This scraper 20a has two opposing rollers 22. It is preferred that at least one of the rollers 22, and in particular both rollers 22, is pressurized (indicated by arrows 24) so ​​that pressure is exerted on the film 12". The scraper 20a further removes impregnating agent 14 from the film 12", exemplified by the droplet 14'. The separated impregnating agent 14' falls into a collection tray 32, which collects the impregnating agent 14".

[0045] The separating device 18, in particular, implements a predefined loading of the film 12 with impregnating agent 14. The illustrated embodiment of the separating device 18 with scrapers 20a, 20b represents only one preferred possibility. Embodiments of the separating device 18 with one or more scrapers; different scraper designs (see, for example, the following) are also possible. Fig. 2a-2c ); different arrangements of the wipers; and / or different adjusting devices for the wipers are possible. The adjusting devices of the wipers 20a, 20b are described in Figure 1The positioning device is shown schematically by arrows 24 for wiper 20a and 29 for wiper 20b. Preferably, the positioning device is adjustable. The positioning device can, for example, be a pneumatic device, a hydraulic device, a spring device, an elastomer, a pressure screw, and / or a fine adjustment thread. The positioning device preferably allows the distance and / or angle and / or pressure between the wiper elements, shown between rollers 22 or pressure plate 26 and pressure surface 28, to be changed.

[0046] A film guide is implemented using the deflection rollers 34, the feed roller 36, and the discharge roller 38. Various configurations are possible. The feed roller 36 and / or the discharge roller 38 can be driven.

[0047] After the film has passed the illustrated wiper 20a, a film 12‴ is in a desired loading state.

[0048] The film 12‴ is subsequently tested in a test device 46. In particular, the loading status of the film 12‴ is checked, preferably measured. The test device 46 is shown to have a scale 44 for weighing the film 12‴. Specifically, a section of the film 12‴ is weighed. Furthermore, the test device 46 is shown to have an optical testing device 42, such as a camera. Loading the film 12‴ generally changes its appearance. For example, the film 12‴ becomes more transparent with increasing loading with impregnating agent. This can be detected by the optical testing device 42. Instead of the test device 46 shown, other designs are also possible, for example, a test device 46 with only one scale 44 or only one optical testing device 42. An otherwise identical design of the device 10 without a test device 46 is also possible.

[0049] The foil 12‴ is then wound onto the output roller 38. The output roller 38 rotates counterclockwise (arrow 60).

[0050] It is possible to combine an active ingredient, e.g., scopolamine, with the film 12‴ before and / or after it is wound up. This can be achieved either by combining another layer of film containing the active ingredient with the film 12‴, or by directly combining the active ingredient with the film 12‴, e.g., as a coating. This allows for the creation of a transdermal therapeutic system.

[0051] Figures 2a-2c Figures 20c, 20d, and 20e show exemplary alternative designs of a wiper. These wipers 20c, 20d, and 20e can, for example, replace wiper 20b at position II in Figure 1 be used.

[0052] Figure 2aFigure 1 shows a wiper 20c with a pressure surface 28 and a pressure plate 26 arranged opposite it. The pressure plate 26 is adjustable, particularly relative to the pressure surface 28. For example, the angle (arrow 30a) of the pressure plate 26 can be changed. An angle between +90° and -90° from the guideline 31 is possible. Preferably, it is adjustable with an angle between +45° and -45°. The distance (arrow 30b) between the pressure plate 26 and the pressure surface 28 is also adjustable. This allows, for example, the pressure to be changed. This can be achieved, for example, by means of a spring device and / or an adjusting screw. Furthermore, it is shown that an offset (arrow 30c) between the pressure plate 26 and the pressure surface 28 is adjustable. In alternative, preferred embodiments, only one or more of the adjustment options are available.It is also preferably possible to implement the adjustment options with other wiper designs.

[0053] Figure 2b Figure 1 shows a one-sided scraper 20d with a pressure plate 26 that is brought into contact with the film 12" and thereby removes impregnating agent.

[0054] Figure 2c Figure 20e shows a further embodiment of a scraper 20e, wherein two opposing, inclined pressure plates 26 come into contact on both sides with the film 12" and / or the impregnating agent and thus remove impregnating agent.

[0055] Figure 3 Figure 1 shows a further embodiment of a device 10 according to the invention for impregnating a film 12. The device is made of Figure 3 is at least partially designed in a comparable manner to device 10 from Figure 1 (see above).

[0056] The device 10 has a mounting plate 52 arranged over a stand 54 having two feet 56, to which at least some of the components of the device 10 are attached.

[0057] Slide 12' is fed into the figure from the right and executed on the left, slide 12‴.

[0058] The device 10 has several scrapers 20e-20h of a separating device with which impregnating agent is removed from the film 12'.

[0059] The wipers 20e, 20h are designed as roller pair wipers, preferably the pressure being adjustable by means of adjusting devices 50e, 50h.

[0060] The wiper 20e has a pressure plate 26 and a pressure surface 28, in particular the angle of the pressure plate 26 is variable.

[0061] The scraper 20f has two pressure plates 26, which are shown arranged slightly offset. A corresponding arrangement without offset or with a larger offset is also possible. Furthermore, the angle of one or both pressure plates 26 can be varied.

[0062] The deflection pulleys 34 can be varied, in particular via adjusting devices 48.

[0063] The inventive method for producing a transdermal therapeutic system can preferably be combined with one or more features of the Figures 1-3 be performed.

Claims

1. A method for manufacturing a transdermal therapeutic system, comprising the step of: impregnating a film (12), wherein the impregnation of the film (12) comprises the following steps: - feeding the film (12) to be impregnated; - immersing the film (12) into an impregnating agent (14) arranged in an immersion basin (16); and - partially separating, in particular wiping off, the impregnating agent (14) from the film (12) in order to achieve a predefined loading of the film (12) with impregnating agent (14); the method further comprising the step of adding an active ingredient into and / or onto the film (12).

2. A device system for manufacturing a transdermal therapeutic system, comprising a device (10) for impregnating a film (12), the device (10) comprising: an immersion basin (16) filled with impregnating agent (14); a film guiding for feeding a film (12) to be impregnated, immersing the film (12) into the immersion basin (16), and feeding the film (12) out; and a separating device (18) for separating the impregnating agent (14) from the film (12) in order to achieve a predefined loading of the impregnated film (12) with impregnating agent (14). characterized in that the device system further comprises an active ingredient supply device for adding an active ingredient into and / or onto the impregnated film (12).

3. The method according to claim 1, characterized in that the separation of the impregnating agent (14) is effected by means of a separating device (18).

4. The method according to claim 3 or the device system according to claim 2, characterized in that the separating device (18) comprises at least one wiper, preferably coated with silicone.

5. The method or the device system according to claim 4, characterized in that the wiper comprises at least one edge and / or at least one roller.

6. The method or the device system according to claim 4 or 5, characterized in that the in particular pressurized wiper is arranged on both sides of the film (12) loaded with impregnating agent (14).

7. The method according to any one of claims 3-6 or the device system according to any one of claims 2 or 4-6, characterized in that the separating device (18) is configured to be variably adjustable so that the predefined loading be achieved by separating the impregnating agent (14).

8. The method according to claim 7 or the device system according to claim 7, characterized in that the separating device (18) comprises at least one adjusting device for adjusting a pressure and / or a distance, in particular of the wiper, the adjusting device preferably comprising: a pneumatic device, a hydraulic device, a spring device, an elastomer, a pressure screw and a fine adjustment thread.

9. The method according to any one of claims 3-8 or the device system according to any one of claims 2 or 4-8, characterized in that the separating device (18) is arranged such that the separated impregnating agent (14) is returned to the immersion basin (16), in particular falls into the immersion basin (16).

10. The method according to any one of claims 1 or 3-9 or the device system, characterized by a collecting tray, preferably connected to the immersion basin (16), for collecting the separated impregnating agent (14).

11. The method according to any one of claims 1 or 3-10 or the device system according to any one of claims 2 or 4-10, characterized in that the impregnating agent (14) comprises oil, preferably mineral oil, in particular consists thereof.

12. The method according to any one of claims 1 or 3-11 or the device system according to any one of claims 2 or 4-11, characterized in that the film (12) is a porous film (12), in particular comprising polypropylene.

13. The method according to any one of claims 1 or 3-12, characterized in that the method comprises the following further step: - performing in particular an optical and / or weight-recording process control for testing the film (12) loaded with impregnating agent (14).

14. The method according to any one of claims 1 or 3-13 or the device system according to any one of claims 2 or 4-12, characterized by a testing device (46), in particular comprising a scale (44) and / or an optical control device (42), for testing the film (12) loaded with impregnating agent (14).

15. The method according to any one of claims 1 or 3-14 or the device system according to any one of claims 2, 4-12 or 14, characterized in that when the active ingredient is added, the film (12) is coated with an, in particular liquid, active ingredient and / or the film (12) is combined with one or more films containing active ingredients to form a film composite.