Shivakumar H N, Patel R, Desai B G
Department of Pharmaceutical Technology, K. L. E. S's College of Pharmacy, Rajajinagar, 2 Block, Bangalore-560 010, India.
Indian J Pharm Sci. 2008 May-Jun;70(3):408-13. doi: 10.4103/0250-474X.43024.
A central composite design was employed to produce microcapsules of propranolol hydrochloride by o/o emulsion solvent evaporation technique using a mixture of cellulose acetate butyrate as coat material and span-80 as an emulsifier. The effect of formulation variables namely levels of cellulose acetate butyrate (X(1)) and percentage of Span-80 (X(2)) on encapsulation efficiency (Y(1)), drug release at the end of 1.5 h (Y(2)), 4 h (Y(3)), 8 h (Y(4)), 14 h (Y(5)), and 24 h (Y(6)) were evaluated using the F test. Mathematical models containing only the significant terms were generated for each response parameter using multiple linear regression analysis and analysis of variance. Both the formulation variables exerted a significant influence (P <0.05) on Y(1) whereas the cellulose acetate butyrate level emerged as the lone factor which significantly influenced the other response parameters. Numerical optimization using desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of Y(1), Y(2), Y(3), Y(4), Y(5), and Y(6) for the optimized formulation was found to be 92.86+/-1.56% w/w, 29.58+/-1.22%, 48.56+/-2.56%, 60.85+/-2.35%, 76.23+/-3.16% and 95.12+/-2.41%, respectively which were in close agreement with those predicted by the mathematical models. The drug release from microcapsules followed first order kinetics and was characterized by Higuchi diffusion model. The optimized microcapsule formulation developed was found to comply with the USP drug release test-1 for extended release propranolol hydrochloride capsules.
采用中心复合设计，以醋酸丁酸纤维素混合物为包衣材料、司盘 - 80为乳化剂，通过油/油乳液溶剂蒸发技术制备盐酸普萘洛尔微胶囊。使用F检验评估配方变量即醋酸丁酸纤维素水平（X(1)）和司盘 - 80百分比（X(2)）对包封率（Y(1)）、1.5小时末（Y(2)）、4小时（Y(3)）、8小时（Y(4)）、14小时（Y(5)）和24小时（Y(6)）药物释放的影响。使用多元线性回归分析和方差分析为每个响应参数生成仅包含显著项的数学模型。两个配方变量对Y(1)均有显著影响（P <0.05），而醋酸丁酸纤维素水平是显著影响其他响应参数的唯一因素。采用合意性方法进行数值优化，通过对因变量和自变量设置约束来开发优化配方。发现优化配方的Y(1)、Y(2)、Y(3)、Y(4)、Y(5)和Y(6)的实验值分别为92.86±1.56% w/w、29.58±1.22%、48.56±2.56%、60.85±2.35%、76.23±3.16%和95.12±2.41%，与数学模型预测值非常吻合。微胶囊的药物释放遵循一级动力学，并以Higuchi扩散模型为特征。所开发的优化微胶囊配方符合美国药典盐酸普萘洛尔缓释胶囊的药物释放试验 - 1。
