title: Mathematical modelling of liquid transport in swelling pharmaceutical immediate release tablets.
abstract: Oral dosage forms are an integral part of modern health care and account for the majority of drug delivery systems. Traditionally the analysis of the dissolution behaviour of a dosage form is used as the key parameter to assess the performance of a drug product. However, understanding the mechanisms of disintegration is of critical importance to improve the quality of drug delivery systems. The disintegration performance is primarily impacted by the hydration and subsequent swelling of the powder compact. Here we compare liquid ingress and swelling data obtained using terahertz pulsed imaging (TPI) to a set of mathematical models. The interlink between hydration kinetics and swelling is described by a model based on Darcy's law and a modified swelling model based on that of Schott. Our new model includes the evolution of porosity, pore size and permeability as a function of hydration time. Results obtained from two sets of samples prepared from pure micro-crystalline cellulose (MCC) indicate a clear difference in hydration and swelling for samples of different porosities and particle sizes, which are captured by the model. Coupling a novel imaging technique, such as TPI, and mathematical models allows better understanding of hydration and swelling and eventually tablet disintegration.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, West Cambridge Site, Philippa Fawcett Drive, Cambridge CB3 0AS, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Markl
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, West Cambridge Site, Philippa Fawcett Drive, Cambridge CB3 0AS, UK.
authors.forename: Samy
authors.initials: S
authors.lastname: Yassin
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, West Cambridge Site, Philippa Fawcett Drive, Cambridge CB3 0AS, UK.
authors.forename: D Ian
authors.initials: DI
authors.lastname: Wilson
authors.affiliation: GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Goodwin
authors.affiliation: GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Anderson
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, West Cambridge Site, Philippa Fawcett Drive, Cambridge CB3 0AS, UK. Electronic address: jaz22@cam.ac.uk.
authors.forename: J Axel
authors.initials: JA
authors.lastname: Zeitler
mesh_terms: D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005079:Excipients; D008962:Models, Theoretical; D016062:Porosity; D011208:Powders; D012995:Solubility; D013607:Tablets
chemical_list: D005079:Excipients; D011208:Powders; D013607:Tablets
keywords: Liquid penetration; Porosity; Powder compacts; Swelling; Tablet disintegration; Terahertz pulsed imaging