Calculation of the required size and shape of hydroxypropyl methylcellulose matrices to achieve desired drug release profiles

The aim of this study was to develop methods for the design of hydroxypropy l methylcellulose (HPMC) tablets with specified drugs profiles. This was ac hieved by the use of a mathematical model developed to predict the release kinetics of water-soluble drugs from HPMC matrices. The required model para meters were determined experimentally for propranolol HCl and chlorpheniram ine maleate in 0.1 N HCl and phosphate buffer pH 7.4, respectively. Then, t he effects of the dimensions and aspect ratio (radius/height) of the tablet s on the drug release rate were evaluated. Independent experiments were con ducted to verify the theoretical predictions. Acceptable agreement between theory and experiment was found, irrespective of the type of release medium and drug. However, statistical analysis revealed a structure in the result ing residuals. Drug release rates are overestimated at the beginning and un derestimated at the end of the process. Possible explanations and modificat ions of the model are thoroughly discussed. Both. theoretical and experimen tal data showed that a broad spectrum of drug release patterns can be achie ved by varying the size and shape of the tablet. The effect of the initial matrix radius on release was found to be more pronounced than the effect of the initial thickness. The practical benefit of the proposed method is to predict the required size and shape of new controlled drug delivery systems to achieve desired release profiles. thus significantly facilitating the d evelopment of new pharmaceutical products. (C) 2000 Elsevier Science B.V. A ll rights reserved.