A MELT-EXTRUSION PROCESS FOR MANUFACTURING MATRIX DRUG-DELIVERY SYSTEMS

A novel melt-extrusion process was developed to prepare matrix drug de livery systems. The disks contained drugs suspended in various polymer s or polymer/additive combinations. Theophylline , was incorporated in to polyethylene (PE), polycaprolactone (PC): polyvinyl acetate (PVA), and cellulose acetate butyrate (CAB) at a 50% drug loading. There was an 8-fold difference in the effective diffusion coefficient (D-e) betw een the various polymers (from 1.17 x 10(-12) to 7.63 x 10(-12) cm(2)/ h). Increasing the theophylline load from 50 to 70% in PC and PE disks increased the D-e at least 10-fold. Disks with a solids content above 70% by weight could not be made. To modify the release, soluble parti culate additives, that did not melt al the working temperature, were i ncorporated in the PE disks. The soluble, particulate additives reduce d the D-e significantly, and decreased the ease with which the melted mass could be extruded. To improve the ease of manufacture, the partic ulate additives were replaced with polyethylene glycols that melted at the working temperatures. The D-e for the PC/PEG disks were approxima tely 10 times larger than those for the PC disks. In addition to theop hylline, chlorpheniramine maleate and salicylic acid were also incorpo rated into PC disks. The release of the three drugs in water: a pH 1.2 buffer, and a pH 7.5 buffer was determined. The effects of drug type and media on the drug release rates were explained using the drug's so lubility, mean particle size: and dissociation constant. (C) 1997 Else vier Science B.V.