title: Preparation of sustained release co-extrudates by hot-melt extrusion and mathematical modelling of in vitro/in vivo drug release profiles.
abstract: Aim of this work was to develop a cylindrical co-extrudate characterised by an in vivo sustained release profile by means of a hot-melt extrusion process. Co-extrudate was made up of two concentric extruded matrices: an inner one having a hydrophilic character, based on polyethylene glycol, and an outer one with lipophilic character, based on microcrystalline wax. Both segments contained theophylline as a model drug. A screening between several devices differing for dimensions (diameter and length) and relative proportions of the inner and outer part was carried out on the basis of their in vitro drug release and the release mechanism was studied by means of a mathematical model. The co-extrudate exhibiting the desired sustained release was selected for in vivo bioavailability studies. In vivo studies confirmed the achievement of the purpose of the research, demonstrating the desired release of theophylline on four healthy volunteers. Accordingly, hot-melt extrusion process is a viable method to produce in a single step co-extrudates showing a sustained release. In addition, the developed mathematical model proved to be a reliable descriptor of the both in vitro and in vivo experimental data.
authors.affiliation: Department of Pharmaceutical Sciences, University of Trieste, P. le Europa 1, I-34127 Trieste, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Quintavalle
authors.forename: D
authors.initials: D
authors.lastname: Voinovich
authors.forename: B
authors.initials: B
authors.lastname: Perissutti
authors.forename: F
authors.initials: F
authors.lastname: Serdoz
authors.forename: G
authors.initials: G
authors.lastname: Grassi
authors.forename: A
authors.initials: A
authors.lastname: Dal Col
authors.forename: M
authors.initials: M
authors.lastname: Grassi
mesh_terms: D000328:Adult; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D006358:Hot Temperature; D006801:Humans; D007785:Lactose / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000737:chemistry; D013806:Theophylline / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D014885:Waxes / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D014885:Waxes; D011092:Polyethylene Glycols; D013806:Theophylline; D007785:Lactose