title: Controlled drug release from melt-extrudates through processing parameters: a chemometric approach.
abstract: The objective of this study was to tailor a drug release profile through the adjustment of some key processing parameters involved in melt-extrusion: die temperature, shear rate, die length and drug particle size. Two experimental designs were selected, namely a 2-level full factorial design to examine the effects and significance of the processing factors, and a central composite design of the surface responses to find the best set of factor levels to obtain given specifications of drug release. Extrudates of poly(ethylene-co-vinyl acetate) and phenylpropanolamine hydrochloride were prepared using a ram extruder. Drug release profiles from the matrix systems were fitted using a power law, for which a new mathematical expression of a burst release was provided. The burst release and exponent were selected as the responses. The processing factors had a drastic influence on the drug release. Within the domain that was investigated, the burst release and the exponent varied from 6 to 54% and 0.1 to 0.4, respectively, resulting in a time requires for 50% drug release extending from hours to weeks. These results demonstrated the possibilities of modulating the release profile by means of the processing parameters rather than through the classical approach of altering the formulation.
authors.affiliation: School of Pharmaceutical Sciences, Ecole de Pharmacie Genève-Lausanne, University of Geneva, University of Lausanne, 1211 Geneva 4, Switzerland.
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Sarraf
authors.affiliation: Bracco Suisse, CH-1228 Plan-les-Ouates, Geneva, Switzerland.
authors.forename: Samir
authors.initials: S
authors.lastname: Cherkaoui
authors.affiliation: School of Pharmaceutical Sciences, Ecole de Pharmacie Genève-Lausanne, University of Geneva, University of Lausanne, 1211 Geneva 4, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
authors.affiliation: School of Pharmaceutical Sciences, Ecole de Pharmacie Genève-Lausanne, University of Geneva, University of Lausanne, 1211 Geneva 4, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
authors.affiliation: School of Pharmaceutical Sciences, Ecole de Pharmacie Genève-Lausanne, University of Geneva, University of Lausanne, 1211 Geneva 4, Switzerland. Electronic address: eric.doelker@unige.ch.
authors.forename: Eric
authors.initials: E
authors.lastname: Doelker
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D010665:Phenylpropanolamine / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D013678:Technology, Pharmaceutical
chemical_list: D003692:Delayed-Action Preparations; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D010665:Phenylpropanolamine
keywords: Controlled release; Experimental design; Hot-melt extrusion; Phenylpropanolamine hydrochloride; Phenylpropanolamine hydrochloride (CAS Number: 700-65-2); Poly(ethylene-co-vinyl acetate); Poly(ethylene-co-vinyl acetate) syn. Ethylene/vinyl acetate copolymer (CAS No. 24937-78-8); Processing parameters