METHOD FOR PRODUCING ACTIVE AGENT ADMINISTERING SYSTEMS BY MEANS OF PAD PRINTING PROCESSES

Abstract

The present invention relates to a pad printing method for producing an administration form for a pharmaceutical active agent, wherein the method comprises providing a substrate of the administration form and transferring the active agent by means of a pad from a cliché onto the substrate, wherein the area of the cliché is larger than the active-agent-containing area printed onto the substrate. This method is especially suitable for producing transdermal therapeutic systems with volatile active agents. The present invention also relates to arrangements by means of which a method of this kind can be implemented.

Claims

1. A pad printing method for producing an administration form for a pharmaceutical active agent, comprising providing a substrate of the administration form and transferring the active agent by means of a pad from a cliché onto the substrate, wherein the area of the indentation of the cliché is larger than the area of the active-agent-containing imprint printed onto the substrate.

2. The pad printing method according to claim 1, characterised in that the cliché is circular and has a diameter which is at least 5 mm larger than the diameter of the active-agent-containing imprint printed onto the substrate.

3. The pad printing method according to claim 1, characterised in that the administration form is a transdermal therapeutic system (TTS).

4. The pad printing method according to claim 1, characterised in that the substrate to which the pharmaceutical active agent is applied by means of a pad has an upper layer formed from adhesive to which the active agent is applied.

5. The pad printing method according to claim 4, characterised in that the pharmaceutical active agent is formulated for the transfer onto the substrate comprising an adhesive in the form of a polyacrylate adhesive.

6. The pad printing method according to claim 1, characterised in that the pharmaceutical active agent has a boiling point of at most 250° C. at a pressure of 101.3 kPa.

7. The pad printing method according to claim 6, characterised in that the pharmaceutical active agent is present in the form of nicotine.

8. The pad printing method according to claim 6, characterised in that the pharmaceutical active agent is present in the form of a mixture of essential oils or contains an essential oil or an ester thereof.

9. The pad printing method according to claim 6, characterised in that the printed active agent is then covered by an active-agent-impermeable backing layer.

10. (canceled)

11. (canceled)

12. An arrangement for applying an active agent to a substrate with the aid of a pad printing system, comprising a device with a pad and a cliché, wherein the cliché is filled at least in part with an active-agent-containing formulation, and a substrate for receiving the active-agent-containing formulation from the pad from the device, wherein the device is adapted such that of the pad is smaller than the area of an indentation of the cliché.

13. The arrangement according to claim 12, comprising a storage container for storing the active-agent-containing formulation and means for introducing the formulation into the cliché.

14. The arrangement according to claim 12, wherein the active-agent-containing formulation contains an active agent with a boiling point of at most 250° C. at a pressure of 101.3 kPa.

15. The pad printing method according to claim 1, characterised in that the cliché is circular and has a diameter which is at least 10 mm larger than the diameter of the active-agent-containing imprint printed onto the substrate.

16. The pad printing method according to claim 1, characterised in that the cliché is circular and has a diameter which is at least 25 mm larger than the diameter of the active-agent-containing imprint printed onto the substrate.

17. The pad printing method according to claim 5, characterised in that the adhesive is a pressure sensitive adhesive.

18. The arrangement according to claim 12, wherein the active agent is in the form of nicotine.

Description

EXAMPLES

[0051] All examples were produced in accordance with the following provisions:

[0052] The amounts specified in Table 1 of nicotinic basic polymethacrylate solution (41.7% basic polymethacrylate, 58.3% nicotine) were printed with the aid of a pad printing system onto a laminate consisting of a lowermost removable polyethylene terephthalate (PET) film 100 μm thick, a skin contact layer formed from 98% polyacrylate and 2% medium-chain triglycerides (40 g/m.sup.2 weight per unit area) and an adhesive layer formed from 78% polyacrylate, 20% basic polymethacrylate and 2% medium-chain triglycerides (220 g/m.sup.2 weight per unit area). The adhesive surface was printed here directly. The printed adhesive surface was then covered by the adhesive surface of a laminate formed from an adhesive layer formed from 78% polyacrylate, 20% basic polymethacrylate and 2% medium-chain triglycerides (110 g/m.sup.2 weight per unit area) on a polyethylene terephthalate (PET) film 15 μm thick. TTS formats were then stamped, and the TTS were separated.

TABLE-US-00001 TABLE 1 Comparative examples according to the prior art versus results according to the teaching of the invention Material Cliché depth Printed application [μm]/ image [mg] Example Pad diameter diameter according to no. TTS area hardness [mm] [mm] gravimetric IPK  1* 10 cm.sup.2 TTS/30 mg 3 shore 162.5/27.sup.  Not 21.8-22.0 (pointed) determined weight not since weight reached not reached  2* 10 cm.sup.2 TTS/30 mg 3 shore 180/27 Not 25.9 weight (pointed) determined not reached since weight not reached  3* 10 cm.sup.2 TTS/30 mg 3 shore 190/27 27 27.9-28.6 “dry (pointed) rubber imprint” visible on the web  4* 10 cm.sup.2/30 mg 3 shore 190/27 Not 27.5-27.7 “dry (pointed) determined rubber since weight imprint” not reached visible on the web  5* 10 cm.sup.2/30 mg 3 shore 190/27 Not 26.8-27.0 “dry (rounded) determined rubber since weight imprint” not reached visible on the web, many splashes  6* 10 cm.sup.2/30 mg 3 shore 210/27 27 28.1-28.6 “dry (pointed) rubber imprint” visible on the web  7* 10 cm.sup.2 TTS/30 mg 9 shore 200/27 27 29.0-31.1 (pointed) Very large amount of excess material on cliché and slide  8* 10 cm.sup.2/30 mg 3 shore 180/27 Not 25.9 weight (pointed) determined not reached since weight not reached  9.sup.1 10 cm.sup.2 TTS/30 mg 6 shore 162.5/32.sup.  29-30.0 29.3-30.9 10.sup.1 10 cm.sup.2 TTS/30 mg 3 shore 162.5/32.sup.  29-31.0 29.7-30.9 11.sup.1 20 cm.sup.2 TTS/60 mg 6 shore 175/49 40-41.5 58.0-61.1 12.sup.1.2 20 cm.sup.2 TTS/60 mg 6 shore 175/49 40-41.5 59.0-60.6 13.sup.1 30 cm.sup.2 TTS/90 mg 6 shore 180/56 47-49   86.6-90.4 14.sup.1.3 30 cm.sup.2 TTS/90 mg 6 shore 180/56 47-49   88.2-92.0 *= prior art; .sup.1= according to the invention; .sup.2= repeat of 11; .sup.3= repeat of 13

[0053] The prior art products were produced in accordance with the general provisions from OS DE 37 27 214 and EP 0 303 025.

[0054] In comparative examples 1, 2, 4, 5 and 8, only an insufficient material application was achieved. In comparative examples 3, 6 and 7, a material application satisfying the pharmaceutical requirements was achieved. In these examples, however, significant production problems were encountered, because the adhesive surface did not take on the entire nicotine solution that had been transferred to the pad. As a result, the residues still remaining on the pad after the printing process formed a protrusion and extended beyond the surface of the cliché indentation.

[0055] This is avoided by the geometry, i.e. by the larger cliché diameter in comparison to the printed image, as shown in Examples 9-14; no production problems were observed in these cases.