Controlled drug delivery from swellable hydroxypropylmethylcellulose matrices: model-based analysis of observed radial front movements.
This work is related to the on-going development of mathematical models describing transient drug delivery from hydroxypropylmethylcellulose (HPMC) matrices. Recently, experimental data providing a detailed mapping of radial swelling, diffusion, and erosion front movements in a high-viscosity HPMC matrix were published [J. Controlled Release 70 (2001) 383]. Using these and other data for verification of simulations, a detailed mathematical model, taking into account water-induced swelling, drug dissolution, and external and internal mass transport resistances of dissolved drug, has been developed. In contrast to earlier models, explicit equations for the rate of movement of the swelling, diffusion and erosion fronts, with the relevant physical properties of drug and HPMC matrix contained in the equations, were derived. Simulations have been compared to transient experimental data for three drugs of very different water solubility and a good agreement was found, taking into account the uncertainty of key input parameters. Furthermore, the model predicts the presence of the drug particle translocation phenomenon observed experimentally. However, continued swelling of the matrix, subsequent to the disappearance of the swelling front, could not be described by the present model. The front-tracking approach illustrated is of relevance in the development of detailed and accurate models of drug delivery from swellable cylindrical matrices involving both axial and radial diffusion.
Kiil
Søren
S
Department of Chemical Engineering, Technical University of Denmark, Building 229, DK-2800 Kgs., Lyngby, Denmark. sk@kt.dtu.dk
Dam-Johansen
Kim
K
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004008:Diclofenac / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008433:Mathematics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry*; D008956:Models, Chemical; D012680:Sensitivity and Specificity; D013997:Time Factors
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004008:Diclofenac; D065347:Hypromellose Derivatives; D008747:Methylcellulose