title: Predicting drug release from HPMC/lactose tablets.
abstract: Three mathematical models were applied to quantify drug release from HPMC/lactose-based matrix tablets loaded with varying amounts of theophylline: (i) a numerical model considering drug diffusion in axial and radial direction in cylinders as well as limited drug solubility effects, (ii) an analytical solution of Fick's second law of diffusion considering axial and radial mass transport in a cylinder, but neglecting limited drug solubility effects, and (iii) a simple early time approximation of the analytical solution, considering only radial mass transport and neglecting axial diffusion as well as limited drug solubility effects. The three models were fitted to experimentally determined drug release kinetics from various types of tablets in 0.1M HCl and phosphate buffer pH 7.4. Interestingly, the agreement between fitted theories and experimental data was similar in all cases. However, the determined system specific model parameters (apparent diffusion coefficients of theophylline in the polymeric matrices) were significantly biased when using simplified theories. Nevertheless, the reliability of theoretical predictions was similar for all three models, since the determined apparent diffusivities are partially "lumped" parameters. Thus, from a practical point of view, very simple equations can be used during product optimization, allowing estimating the effects of formulation parameters on drug release.
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France. juergen.siepmann@univ-lille2.fr
authors.forename: J
authors.initials: J
authors.lastname: Siepmann
authors.forename: Y
authors.initials: Y
authors.lastname: Karrout
authors.forename: M
authors.initials: M
authors.lastname: Gehrke
authors.forename: F K
authors.initials: FK
authors.lastname: Penz
authors.forename: F
authors.initials: F
authors.lastname: Siepmann
mesh_terms: D004058:Diffusion; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007785:Lactose / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008962:Models, Theoretical; D015203:Reproducibility of Results; D012995:Solubility; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D005079:Excipients; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D013806:Theophylline; D007785:Lactose