HPMC-matrices for controlled drug delivery: a new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics.
OBJECTIVE
The purpose of this study was to investigate the drug release mechanisms 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 water 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 drug release studies) was obtained, proving the validity of the presented model. The water and drug diffusivities are strongly dependent on the matrix swelling ratio. Diffusion, swelling and dissolution are the governing mechanisms involved in the overall drug release process.


CONCLUSIONS
The practical benefit of the presented model is to identify the required shape and dimensions of drug-loaded HPMC-matrices in order to achieve desired release profiles, thus facilitating the development of new controlled drug delivery products. This will be demonstrated in a future study.
Siepmann
J
J
College of Pharmacy, Freie Universität Berlin, Germany. siepmann@zedat.fu-berlin.de
Kranz
H
H
Bodmeier
R
R
Peppas
N A
NA
D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D010078:Oxazines; D011433:Propranolol / Q000737:chemistry*; D015203:Reproducibility of Results; D012995:Solubility; D013997:Time Factors
D003692:Delayed-Action Preparations; D010078:Oxazines; D008747:Methylcellulose; C071191:MK 458; D011433:Propranolol; D007785:Lactose