title: Predictability of drug release from water-insoluble polymeric matrix tablets.
abstract: The purpose of this study was to extend the predictability of an established solution of Fick's second law of diffusion with formulation-relevant parameters and including percolation theory. Kollidon SR (polyvinyl acetate/polyvinylpyrrolidone, 80/20 w/w) matrix tablets with various porosities (10-30% v/v) containing model drugs with different solubilities (Cs=10-170 mg/ml) and in different amounts (A=10-90% w/w) were prepared by direct compression and characterized by drug release and mass loss studies. Drug release was fitted to Fick's second law to obtain the apparent diffusion coefficient. Its changes were correlated with the total porosity of the matrix and the solubility of the drug. The apparent diffusion coefficient was best described by a cumulative normal distribution over the range of total porosities. The mean of the distribution coincided with the polymer percolation threshold, and the minimum and maximum of the distribution were represented by the diffusion coefficient in pore-free polymer and in aqueous medium, respectively. The derived model was verified, and the applicability further extended to a drug solubility range of 10-1000 mg/ml. The developed mathematical model accurately describes and predicts drug release from Kollidon SR matrix tablets. It can efficiently reduce experimental trials during formulation development.
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Grund
authors.forename: Martin
authors.initials: M
authors.lastname: Körber
authors.forename: Roland
authors.initials: R
authors.lastname: Bodmeier
mesh_terms: D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D008962:Models, Theoretical; D016062:Porosity; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
chemical_list: D004337:Drug Carriers; D013607:Tablets; D011205:Povidone
keywords: Controlled release; Diffusion; Direct compression; KSR; Kollidon SR; Mathematical modeling; Matrix tablets; PVAc; PVP; Percolation threshold; Polyvinyl acetate matrix; Water-soluble drugs; polyvinyl acetate; polyvinylpyrrolidone