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

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Abstract
Hot-melt screw extrusion was presented as an alternative method for producing polymer-based sustained release pellets. Special care was paid to the case of highly dosed freely soluble drugs which often pose technological problems with the usual manufacturing processes. In a preformulation study, polymers, plasticizers and drugs were selected according to various criteria including thermal stability. During these preliminary tests, the optimum extrusion conditions were defined. Four polymers were considered for extrusion trials, namely ethylcellulose, cellulose acetate butyrate, poly(ethylene-co-vinyl acetate) and a polymethacrylate derivative (Eudragit® RSPM). Pellets were produced with diltiazem hydrochloride as model drug. The surface appearance of various formulations was examined and the porosity assessed by means of mercury porosimetry. A distinct structure was found for the EVAC-based pellets. The overall porosity was less than 10%. Lastly, in vitro release of the drug showed a biphasic profile with a slow diffusion-controlled phase following a much faster release. The release rate of diltiazem hydrochloride from EVAC-based hot-melt extruded pellets of size 2 × 2 mm was very low. It is the opinion of the authors that this type of dosage form offers many potentialities because of its ease of processing and the wide possibility of modulating the release through the addition of hydrophilic excipients.