title: Release behaviour of clozapine matrix pellets based on percolation theory.
abstract: The release behaviour of clozapine matrix pellets was studied in order to investigate if it is possible to explain it applying the concepts of percolation theory, previously used in the understanding of the release process of inert and hydrophilic matrix tablets. Thirteen batches of pellets with different proportions of clozapine/microcrystalline cellulose (MCC)/hydroxypropylmethyl cellulose (HPMC) and different clozapine particle size fractions were prepared by extrusion-spheronisation and the release profiles were studied. It has been observed that the distance to the excipient (HPMC) percolation threshold is important to control the release rate. Furthermore, the drug percolation threshold has a big influence in these systems. Batches very close to the drug percolation threshold, show a clear effect of the drug particle size in the release rate. However, this effect is much less evident when there is a bigger distance to the drug percolation threshold, so the release behaviour of clozapine matrix pellets is possible to be explained based on the percolation theory.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Seville, 41012 Seville, Spain. aguilardeleyva@us.es
authors.forename: Angela
authors.initials: A
authors.lastname: Aguilar-de-Leyva
authors.forename: Tahmer
authors.initials: T
authors.lastname: Sharkawi
authors.forename: Bernard
authors.initials: B
authors.lastname: Bataille
authors.forename: Gilles
authors.initials: G
authors.lastname: Baylac
authors.forename: Isidoro
authors.initials: I
authors.lastname: Caraballo
mesh_terms: D014150:Antipsychotic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003024:Clozapine / Q000737:chemistry*; D004304:Dosage Forms; D004337:Drug Carriers; D004339:Drug Compounding; D057927:Hydrophobic and Hydrophilic Interactions; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D010316:Particle Size; D012212:Rheology; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D014150:Antipsychotic Agents; D004304:Dosage Forms; D004337:Drug Carriers; D065347:Hypromellose Derivatives; D002482:Cellulose; D008747:Methylcellulose; D003024:Clozapine; C109691:microcrystalline cellulose