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8624805 
Journal Article 
Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials 
Follonier, N; Doelker, E; Cole, ET 
1995 
Yes 
Journal of Controlled Release
ISSN: 0168-3659
EISSN: 1873-4995 
ELSEVIER SCIENCE BV 
AMSTERDAM 
36 
3 
243-250 
English 
WOS:A1995TB21400007 
Sustained release pellets were prepared using the continuous process of hot-melt screw extrusion. Diltiazem hydrochloride was used as a highly dosed, freely soluble model drug. Pellets obtained with this technique can be filled into hard gelatin capsules. It was possible to obtain in vitro release rates low enough to achieve therapeutic plasma levels for diltiazem hydrochloride with a once or twice daily administration. Firstly, the release profiles from extrudates varying in their polymer to drug ratio were analysed using a double exponential decay equation in order to discriminate between surface release and diffusion-controlled release phases. Then, to optimize the release profile of the drug the influence of different parameters, such as polymer type, addition of pore-forming additives and hydrophilic polymers, or size of the pellets was studied. With one particular inert polymer, poly (ethylene-co-vinyl acetate), the possibility of achieving a nearly zero order release without any coating was investigated. Assuming first that this could be achieved by incorporating polymers with pH-dependent behaviour, the effect of cationic and enteric additives was also evaluated. Finally, swelling agents were included into the pellets, which were able to reduce the burst release. © 1995. 
Diltiazem hydrochloride; Hot-melt extrusion; Pellet; Poly(ethylene-co-vinyl acetate); Sustained release kinetics