HPMC-matrices for controlled drug delivery: A new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics

Purpose. The purpose of this study was to investigate the drug release mech anisms from hydroxypropyl methylcellulose (HPMC)-matrices, and to develop a new model for quantitative predictions of controlled drug delivery. Methods. The dissolved mass of pure HPMC-matrices and the drug release rate from propranolol HCl-loaded HPMC-matrices were determined experimentally. Based on Fick's second law of diffusion for cylinders, the transport of wat er and drug were modeled considering (i) both radial and axial diffusion, ( ii) concentration-dependent drug diffusivities, (iii) matrix swelling and ( iv) HPMC dissolution. Results. Good agreement between theory and experiment (dissolved mass and d rug release studies) was obtained, proving the validity of the presented mo del. The water and drug diffusivities are strongly dependent on the matrix swelling ratio. Diffusion, swelling and dissolution are the governing mecha nisms involved in the overall drug release process. Conclusions. The practical benefit of the presented model is to identify th e required shape and dimensions of drug-loaded HPMC-matrices in order to ac hieve desired release profiles, thus facilitating the development of new co ntrolled drug delivery products. This will be demonstrated in a future stud y.