Optimization of hydrophilic matrix tablets using a D-optimal design

One method of achieving sustained drug release is by the use of hydrophilic polymeric excipients directly compressed with active ingredients into tablets. Hydrophilic polymers swell in the presence of water to form hydrogel structures from which drugs are released by slow diffusion. The release rate modulation is obtained by the use of different types of polymer alone or in combinations. Optimization of the release rate of propranolol hydrochloride from mixtures containing two hydrophilic polymers: hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (CMCNa) was made by mixture design. Mixing ratios of the two polymers with the active ingredient were selected as formulation factors. Experimental results were examined using a D-optimal quadratic model. Contour plots were formed based an the model to assess the change in the response surface in order to understand the relationship between dependent and independent variables. The results enabled the formulation of tablets with the desired dissolution characteristics together with a fairly complete characterization of the system. Optimization of release rare was performed applying constraints on the cumulative amounts of drug released after 1, 6 and 12 h release time intervals. Optimized formulations presented release rates that were close to the predicted values. Fitting the release data from optimized formulations was performed according to Korsmeyer et al. (1983) and Peppas and Sahlin (1989) kinetic models. Release from optimized formulations occurs mainly by Fickian diffusion but an important fraction of the drug is released by polymer relaxation. (C) 1997 Elsevier Science B.V.