Method for producing an, in particular oral, active substance laminate, and active substance laminate, in particular oral active substance laminate

Abstract

The invention relates to a method for producing an active substance laminate, especially an oral active substance laminate (100), having at least one active-substance-containing layer (31), which is arranged on a substrate (20), wherein the method comprises the following steps: a) providing a substrate (20) having an upper side (21) and an underside (22); b) applying an active-substance-containing mass (24) in a gap (25) formed by a first rotating roller (26) and a second rotating roller (27); c) transporting the substrate (20) to the second roller (27) by means of a third rotating roller (28) in such a way that the active-substance-containing mass (24) is applied to the upper side (21) of the substrate (20) by the second roller (27) in the form of an active-substance-containing layer (31); d) transporting an intermediate laminate (30), formed by the substrate (20) and the active-substance-containing layer (31), to a drying device (40); and e) drying the intermediate laminate (30), especially the active-substance-containing layer (31).

Claims

1. A method for producing an active substance laminate, having at least one active-substance-containing layer, which is arranged on a substrate, wherein the method comprises the following steps: a) providing a substrate having an upper side and an under side; b) applying an active-substance-containing mass in a gap formed by a first rotating roller and a second rotating roller, wherein the gap between the first rotating, roller and the second rotating roller has a width of from 0.2 mm-0.9 mm; c) transporting the substrate to the second roller by means of a third rotating roller in such a way that the active-substance-containing mass is applied to the upper side of the substrate in the form of an active-substance-containing layer to form an intermediate laminate by the second roller, wherein the rotation speed of the first rotating roller is 0.1 m/min-0.5 m/min, the rotation speed of the second rotating roller is 0.8 m/min-2.3 m/min and the rotation speed of the third rotating roller is 0.5 m/min-1.5 m/min, wherein the second roller has a rotation speed greater than the rotation speed of the third roller; d) transporting the intermediate laminate, formed by the substrate and the active-substance-containing layer, to a drying device; e) drying the active-substance-containing layer of the intermediate laminate in the drying device at a temperature of 30-120° C.; and f) guiding the dried intermediate laminate through laminating rollers and forming the active substance laminate.

2. The method according to claim 1, wherein the underside of the substrate is releasably connected, to a carrier film.

3. The method according to claim 1, wherein solvent is removed as the active-substance-containing layer is dried.

4. The method according to claim 1, wherein the substrate is free from an active substance or contains an active substance.

5. The method according to claim 1, wherein the substrate is formed by at least two active-substance-free layers.

6. The method according to claim 1, wherein the first roller, the second roller and the third roller rotate in the same rotation direction.

7. The method according to claim 1, wherein said drying is carried out in a plurality of drying zones having different temperatures by means of an air jet.

8. The method according to claim 1, further comprising: g) rolling up the active substance laminate.

9. The method according to claim 2, further comprising: h) unrolling the active substance laminate; i) optionally removing the carrier film; and j) dividing the active substance laminate into multiple active substance laminate portions.

Description

(1) The invention will be explained in greater detail hereinafter on the basis of exemplary embodiments with reference to the accompanying schematic drawings.

(2) In the drawings:

(3) FIG. 1 shows a cross-section through an oral thin film according to the prior art;

(4) FIG. 2 shows a schematic depiction in respect of a coating method known from the prior art;

(5) FIG. 3 shows a schematic depiction in respect of the method according to the invention; and

(6) FIG. 4 shows a cross-section through an oral active substance laminate according to the invention.

(7) In the description below, like reference signs are used for like and equivalent parts.

(8) FIG. 3 shows schematically the process of the method according to the invention for producing an oral active substance laminate. Especially the individual stations of the method according to the invention are shown.

(9) A, especially active-substance-free, substrate 20 with an upper side 21 and an underside 22 is provided in rolled-up form. Furthermore, a container 23 can be seen, in which there is situated an active-substance-containing mass 24. The active-substance-containing mass 24 is transported to a gap 25. The gap 25 is formed by a first rotating roller 26 and a second rotating roller 27. The gap 25 between the first rotating roller 26 and the second rotating roller 27 has a width of 0.6 mm, for example.

(10) The first rotating roller 26 and the second rotating roller 27 are arranged approximately next to one another, especially in parallel, in the horizontal direction so that a substantially vertically running gap 25 may be formed. A third rotating roller 28 is arranged vertically above the second rotating roller 27. In an alternative embodiment of the method the third rotating roller 28 may also be situated beneath the second rotating roller 27.

(11) In order to ensure that the active-substance-containing mass 24 is transported along the second roller 27 in the direction of the third roller 28, a doctor blade or scraper (not shown) may be formed on the first rotating roller 26. The substrate 20 is transported to the second rotating roller 27 with the aid of the third rotating roller 28 in such a way that the active substance is applied from the surface of the second roller 27 to the upper side 21 of the substrate 20.

(12) The rotation direction R.sub.1 of the first roller 26 and the rotation direction R.sub.2 of the second roller 27 and the rotation direction R.sub.3 of the third roller 28 coincide. The rotation directions R.sub.1, R.sub.2 and R.sub.3 are thus the same. The rotation speeds in the presented example are for the first roller (26) 0.0 m/min-0.5 m/min, for the second roller (27) 0.8 m/min-2.3 m/min, and for the third roller (28) 0.5 m/min-1.5 m/min. The rotation speeds of the first roller 26, the second roller 27 and the third roller 28 have a value within the stated value ranges, wherein all rotation speeds are constant whilst the method according to the invention is being carried out.

(13) The intermediate laminate 30, which is formed by the substrate 20 and the active-substance-containing layer 31, is transported to a drying device 40 with the aid of transport rollers 29. The drying device 40 is a drying channel, for example with five drying zones 41. Each drying zone has an air jet 42. Different temperatures are available in the five drying zones 41 with the aid of the air jets 42, and so the intermediate laminate 30 is acted on in the different drying zones 41 by different temperatures, which lie between 30° C. and 120° C.

(14) The intermediate laminate 31 is transported in the drying device 40 in such a way that the active-substance-containing layer 31 points towards the air jets 42. The substrate 20 is arranged facing away from the air jets 42.

(15) After having passed through the drying device 40, a dried intermediate laminate 32 is provided. This dried intermediate laminate 32 is transported with the aid of transport rollers 29 to laminating rollers 45 and 45′. The laminating roller 45 has a rotation direction R.sub.4, wherein the laminating roller 45 rotates in a clockwise direction. The laminating roller 45′ has the rotation direction R.sub.5, this rotation direction R.sub.5 being anticlockwise in the shown example. R.sub.4 and R.sub.5 therefore do not have the same rotation direction.

(16) After having passed through the laminating rollers 45 and 45′, a dried and strengthened intermediate laminate, i.e. the active substance laminate 33, is thus provided. This dried active substance laminate 33 may be rolled up, and therefore a rolled-up active substance laminate 34 may be provided.

(17) An oral active substance laminate 100 according to the invention is shown in section in FIG. 4.

(18) A carrier film 50 can be seen, however this is merely a part of the oral active substance laminate 100 in an intermediate step of the method according to the invention. The end product does not have a carrier film 50.

(19) The substrate 20 is formed by two active-substance-free layers, specifically the first active-substance-free layer 61 and the second active-substance-free layer 62. The underside of the first active-substance-free layer 61 forms the underside 22 of the substrate 20. The upper side of the second active-substance-free layer 62 forms the upper side 21 of the substrate 20. Alternatively, the substrate 20 might also be formed by active-substance-containing layers. Furthermore, the substrate 20 might be formed by at least one active-substance-containing layer and at least one active-substance-free layer.

(20) An active-substance-containing layer 31 is applied to the upper side 21 of the substrate 20.

(21) The active substance of the active-substance-containing layer 31 may be an analgesic, especially fentanyl and/or buprenorphine, which especially is present as a base or as a salt, and/or oploid antagonist, especially naloxone. The active-substance-free layers 61 and 62, by contrast, may be formed from a polymer and/or a material that swells upon contact with water and/or a water-soluble material.

(22) The active-substance-containing layer 31 for example has an areal density of 60 g/m.sup.2. The active-substance-free substrate layers 61 and 62 by contrast each have an areal density of 120 g/m.sup.2-140 g/m.sup.2.

LIST OF REFERENCE SIGNS

(23) 10 product 11 carrier film 12 matrix 13 surface 14 underside 15 droplet 20, 20′ substrate 21, 21′ upper side 22, 22′ underside 23, 23′ container 24, 24′ active-substance-containing mass 25, 25′ gap 26, 26′ first rotating roller 27, 27′ second rotating roller 28 third rotating roller 28′ transport roller 29, 29′ transport roller 30, 30′ intermediate laminate 31 active-substance-containing layer 32 dried intermediate laminate 33 active substance laminate 34 unrolled active substance laminate 40 drying device 41 drying zone 42 air jet 45, 45′ laminating roller 50 carrier film 61 first layer of the substrate 62 second layer of the substrate 100 oral active substance laminate R.sub.1 rotation direction of the first roller R.sub.2 rotation direction of the second roller R.sub.3 rotation direction of the third roller R.sub.4 rotation direction of the laminating roller 45 R.sub.5 rotation direction of the laminating roller 45′