EVALUATION OF HOT-MELT EXTRUSION AS A NEW TECHNIQUE FOR THE PRODUCTION OF POLYMER-BASED PELLETS FOR SUSTAINED-RELEASE CAPSULES CONTAINING HIGH LOADINGS OF FREELY SOLUBLE DRUGS

Hot-melt screw extrusion was presented as an alternative method for pr oducing polymer-based sustained release pellets. Special care was paid to the case of highly dosed freely soluble drugs which often pose tec hnological problems with the usual manufacturing processes. In a prefo rmulation study, polymers, plasticizers and drugs were selected accord ing to various criteria including thermal stability. During these prel iminary tests, the optimum extrusion conditions were defined. Four pol ymers were considered for extrusion trials, namely ethylcellulose, cel lulose acetate butyrate, poly(ethylene-co-vinyl acetate) and a polymet hacrylate derivative (Eudragit(R) RSPM). Pellets were produced with di ltiazem hydrochloride as model drug. The surface appearance of various formulations was examined and the porosity assessed by means of mercu ry porosimetry. A distinct structure was found for the EVAC-based pell ets. The overall porosity was less than 10 %. Lastly, in vitro release of the drug showed a biphasic profile with a slow diffusion-controlle d phase following a much faster release. The release rate of diltiazem hydrochloride from EVAC-based hot-melt extruded pellets of size 2 x 2 mm was very low. It is the opinion of the authors that this type of d osage form offers many potentialities because of its ease of processin g and the wide possibility of modulating the release through the addit ion of hydrophilic excipients.