Scientific article
English

Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials

Published inJournal of controlled release, vol. 36, no. 3, p. 243-250
Publication date1995
Abstract

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 included into the pellets, which were able to reduce the burst release.

Keywords
  • Pellet
  • Sustained release kinetics
  • Hot-melt extrusion
  • Diltiazem hydrochloride
  • Poly(ethylene-co-vinyl acetate)
Citation (ISO format)
FOLLONIER, Nicolas, DOELKER, Eric, COLE, Ewart T. Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials. In: Journal of controlled release, 1995, vol. 36, n° 3, p. 243–250. doi: 10.1016/0168-3659(95)00041-6
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Article (Published version)
accessLevelRestricted
Identifiers
Journal ISSN0168-3659
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