Crush resistant delayed-release dosage forms

Abstract

The invention relates to a dosage form comprising a physiologically effective amount of a physiologically active substance (A), a synthetic, semi-synthetic or natural polymer (C), optionally one or more physiologically acceptable auxiliary substances (B) and optionally a synthetic, semi-synthetic or natural wax (D), wherein the dosage form exhibits a resistance to crushing of at least 400 N and wherein under physiological conditions the release of the physiologically active substance (A) from the dosage form is at least partially delayed.

1 . A dosage form comprising a physiologically effective amount of a physiologically active substance (A) and a synthetic, semi-synthetic or natural polymer (C), wherein the dosage form exhibits a resistance to crushing of at least 400 N, wherein under physiological conditions the release of the physiologically active substance (A) from the dosage form is at least partially delayed and wherein the physiologically active substance (A) comprises oxycodone, a physiologically acceptable salt thereof, or a physiologically acceptable derivative thereof. 
     
     
         2 . The dosage form according to  claim 1 , which exhibits a resistance to crushing of at least 500 N. 
     
     
         3 . The dosage form according to  claim 1 , which is in the form of a tablet. 
     
     
         4 . The dosage form according to  claim 1 , which is in multiparticulate form, individual particles of said multiparticulate form exhibiting a resistance to crushing of at least 400 N. 
     
     
         5 . The dosage form according to  claim 4 , wherein the particles are pressed into tablets or packaged in capsules. 
     
     
         6 . The dosage form according to  claim 1 , wherein polymer (C) is selected from the group consisting of polyalkylene oxide, polyethylene, polypropylene, polyvinyl chloride, polycarbonate, polystyrene, polyacrylate, the copolymers thereof and mixtures thereof. 
     
     
         7 . The dosage form according to  claim 1 , wherein polymer (C) is an polyalkylene oxide selected from the group consisting of polymethylene oxide, polyethylene oxide, polypropylene oxide, copolymers thereof, block-copolymers thereof, and mixtures of any of the foregoing. 
     
     
         8 . The dosage form according to  claim 6 , wherein polymer (C) has a molecular weight of at least 0.5 million g/mol according to rheological measurements. 
     
     
         9 .- 12 . (canceled) 
     
     
         13 . The dosage form according to  claim 38 , wherein wax (D) has a softening point of at least 50° C. 
     
     
         14 . The dosage form according to  claim 13 , wherein wax (D) is carnauba wax or beeswax. 
     
     
         15 . The dosage form according to  claim 1 , wherein substance (A) is present in a matrix. 
     
     
         16 . The dosage form according to  claim 15 , wherein the matrix comprises polymer (C) and a synthetic semi-synthetic or natural wax (D). 
     
     
         17 .- 19 . (canceled) 
     
     
         20 . A process for the production of a dosage form according to  claim 1  comprising the following steps:
 (a) mixing of component (A), (C), optionally one or more physiologically acceptable auxiliary substances (B) and optionally a synthetic, semi-synthetic or natural wax (D); and   (b) hardening the mixture by applying heat and force, where the heat is supplied during and/or before the application of force and the quantity of heat supplied is sufficient to heat component (C) at least up to its softening point.   
     
     
         21 . The process according to  claim 20 , wherein step (b) is performed by means of a twin-screw-extruder or a planetary-gear extruder. 
     
     
         22 . The process according to  claim 1 , wherein step (c) is performed in a plasticize stated of the mixture of components (A), (C), optionally (B) and optionally (D). 
     
     
         23 . (canceled) 
     
     
         24 . The product of the process of  claim 20 . 
     
     
         25 . The product of the process of  claim 21 . 
     
     
         26 . The product of the process of  claim 22 . 
     
     
         27 .- 33 . (canceled) 
     
     
         34 . The dosage form according to  claim 1 , wherein the physiologically acceptable salt is a hydrochloride. 
     
     
         35 . The dosage form according to  claim 1 , wherein polymer (C) is a polyethylene oxide. 
     
     
         36 . The dosage form according to  claim 1 , wherein the physiologically acceptable derivative is an ester, ether or amide. 
     
     
         37 . The dosage form according to  claim 1 , additionally comprising one or more physiologically acceptable auxiliary substances (B). 
     
     
         38 . The dosage form according to  claim 1 , additionally comprising a synthetic, semi-synthetic or natural wax (D). 
     
     
         39 . The dosage form according to  claim 2 , wherein polymer (C) is an polyalkylene oxide selected from the group consisting of polymethylene oxide, polyethylene oxide, polypropylene oxide, copolymers thereof, block-copolymers thereof, and mixtures of any of the foregoing. 
     
     
         40 . The dosage form according to  claim 37 , wherein polymer (C) has a molecular weight of at least 0.5 million g/mol according to rheological measurements. 
     
     
         41 . The process according to  claim 20 , further comprising the step:
 (c) forming the thus obtained hardened mixture into a tablet.   
     
     
         42 . The process according to  claim 21 , further comprising the step:
 (d) cutting the extruded strand and packaging the thus singulated extrudates into capsules.