Process for the production of an abuse-proofed dosage form

Abstract

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 with at least reduced potential for abuse, said dosage form exhibiting a breaking strength of at least 500 N, said process comprising:
 a) providing a formulation mixture comprising at least one active ingredient with potential for abuse (A) and at least one synthetic or natural polymer (C), wherein the at least one active ingredient with potential for abuse (A) is selected from the group consisting of oxvmorphone, hydromorphone, morphine and physiologically acceptable compounds and derivatives thereof,   b) moistening the mixture with at least a sufficient quantity of a solvent for the polymer (C) to uniformly moisten the mixture,   c) optionally dividing the mixture from step b) into sub-portions,   d) drying the sub-portion(s) from step c) or the mixture from step b) and   e) shaping the dried sub-portion or mixture from step d) to yield the dosage form.   
     
     
         2 . A 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 . A 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 . A 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 . A process according to  claim 3 , where the solvent and the dispersant are miscible with one another. 
     
     
         6 . A process according to  claim 1 , which further comprises incorporating the solvent into the formulation mixture as a foam. 
     
     
         7 . A process according to  claim 6 , which further comprises stabilizing the foam with the assistance of foam stabilizers. 
     
     
         8 . A process according to  claim 6 , which further comprises drying the sub-portion(s) or the mixture in granular form. 
     
     
         9 . A process according to  claim 8 , which further comprises drying the mixture in granular form, and then dividing the dried, granulated mixture into sub-portions, which in each case correspond to the mass of a unit of the dosage form, and shaping to yield the dosage form. 
     
     
         10 . A process according to  claim 1 , which further comprises adding solvent to the formulation mixture in an amount such that a shapeable paste is obtained. 
     
     
         11 . A process according to  claim 10 , which further comprises drying the paste and, before or after it is dried, dividing the paste into sub-portions and shaping or converting into the dosage form the dried portions, optionally after further dividing in each case into a portion corresponding to the mass of a unit of the dosage form. 
     
     
         12 . A process according to  claim 11 , where the sub-portions have the form of strands. 
     
     
         13 . A process according to  claim 12 , which further comprises producing the strands with the assistance of a screen or strand former. 
     
     
         14 . A process according to  claim 12 , which further comprises singulating and shaping dried strands to yield the dosage form. 
     
     
         15 . A process according to  claim 14 , where shaping proceeds with the assistance of a tablet press. 
     
     
         16 . A process according to  claim 12 , which further comprises shaping dried strands with the assistance of shaping rollers or shaping belts equipped with rollers to yield the dosage form. 
     
     
         17 . A process according to  claim 11 , which further comprises converting the paste into a planar structure, from which the dosage form is stamped. 
     
     
         18 . A process according to  claim 10 , where the process is performed with the assistance of an extruder. 
     
     
         19 . A 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. 
     
     
         20 . A process according to  claim 19 , which further comprises converting the solution into a planar structure. 
     
     
         21 . A process according to  claim 20 , 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. 
     
     
         22 . A process according to  claim 19 , which further comprises shaping the dosage form by stamping from the dried planar structure or by calendaring. 
     
     
         23 . A process according to  claim 19 , 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. 
     
     
         24 . A process according to  claim 23 , which further comprises placing the portions in molds corresponding to the shape of a unit of the dosage form. 
     
     
         25 . A process according to  claim 19 , which further comprises dividing the mixture into any desired portions, and, after drying, optionally recombining the portions, and shaping to yield the dosage form. 
     
     
         26 . A process according to  claim 1 , wherein the physiologically acceptable compounds and derivatives are salts, solvates, esters, ethers and amides.