Process for the production of an abuse-proofed dosage form
The present invention relates to a process for the production of an abuse-proofed dosage form containing, apart from one or more active ingredients with potential for abuse and optionally physiologically acceptable auxiliary substances, at least one synthetic or natural polymer (C) with a breaking strength of at least 500 N, wherein the formulation mixture is combined with a solvent for the polymer (C) at least in quantities such that the formulation mixture is at least uniformly moistened, the at least moistened composition is optionally divided into sub-portions, dried and shaped to yield the dosage form.
1. A process for the production of a solid dosage form, said process comprising:
a) producing a formulation mixture by homogeneously mixing (i) at least one active ingredient with potential for abuse selected from the group consisting of oxycodone, oxymorphone, hydrocodone, hydromorphone, morphine, tramadol, (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, and physiologically acceptable salts thereof, and (ii) at least 40 wt. %, based on the weight of the solid dosage form, of at least one polyalkylene oxide (C) having a molecular weight of at least 1,000,000 g/mol and exhibiting a breaking strength of at least 500 N;
b) producing a uniformly moistened formulation mixture by combining the formulation mixture produced in a) with (iii) a solvent for the polyalkylene oxide (C), wherein said solvent is in the form of a foam, the form is stabilized by foam stabilizers, and the solvent is in a quantity sufficient to provide uniform moistening of the formulation mixture;
c) optionally dividing the uniformly moistened formulation mixture into sub-portions;
d) drying the uniformly moistened formulation mixture or the sub-portions to granules; and
e) shaping the granules to produce a solid dosage form that exhibits a breaking strength of at least 500 N and cannot be comminuted using a hammer or with the assistance of a mortar and pestle.
2. The process according to claim 1 , where the dried sub-portions in each case correspond to the mass of a unit of the dosage form.
3. The process according to claim 1 , which further comprises dispersing the formulation mixture in a liquid dispersant in which the polymer component (C) is not soluble before addition of the solvent.
4. The process according to claim 3 , which further comprises dividing the formulation mixture into sub-portions in each case corresponding to the mass of a unit of the dosage form either before or after the formulation mixture is dispersed.
5. The process according to claim 3 , where the solvent and the dispersant are miscible with one another.
6. The process according to claim 1 , which further comprises drying the uniformly moistened formulation mixture to granules, and then dividing the granules into sub-portions, which sub-portions in each case correspond to the mass of a unit of the dosage form, and shaping to yield the dosage form.
7. The process according to claim 1 , which further comprises adding solvent to the formulation mixture in an amount such that a shapeable paste is obtained.
8. The process according to claim 7 , which further comprises drying the paste and, before or after it is dried, the paste is divided into sub-portions and shaping or converting into the dosage form the dried portions, optionally after further dividing each case into a portion corresponding to the mass of a unit of the dosage form.
9. The process according to claim 8 , where the sub-portions have the form of strands.
10. The process according to claim 9 , which further comprises producing the strands with the assistance of a screen or strand former.
11. The process according to claim 9 , which further comprises singulating and shaping dried strands to yield the dosage form.
12. The process according to claim 11 , where shaping proceeds with the assistance of a tablet press.
13. The process according to claim 9 , which further comprises shaping dried strands with the assistance of shaping rollers or shaping belts equipped with rollers to yield the dosage form.
14. The process according to claim 8 , which further comprises converting the paste into a planar structure, from which the dosage form is stamped.
15. The process according to claim 7 , where the process is performed with the assistance of an extruder.
16. The process according to claim 1 , which further comprises adding a quantity of solvent sufficient to dissolve at least the polymer component (C) to the formulation mixture.
17. The process according to claim 16 , which further comprises converting the solution into a planar structure.
18. The process according to claim 17 , which further comprises producing the planar structure with the assistance of an extruder with a flat die or by casting the solution onto a level planar support.
19. The process according to claim 16 , which further comprises shaping the dosage form by stamping from the dried planar structure or by calendaring.
20. The process according to claim 16 , where the mixture is divided into portions such that, after drying, the portions correspond in each case to the mass of a unit of the dosage form.
21. The process according to claim 20 , which further comprises placing the portions in molds corresponding to the shape of a unit of the dosage form.
22. The process according to claim 16 , which further comprises dividing the mixture into any desired portions, and, after drying, optionally recombining the portions, and shaping to yield the dosage form.