Kharia A A, Hiremath S N, Singhai A K, Omray L K, Jain S K
Oriental College of Pharmacy, Raisen Road, Bhopal-462 021, India.
Indian J Pharm Sci. 2010 Sep;72(5):599-606. doi: 10.4103/0250-474X.78527.
The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.
本研究的目的是设计并优化阿昔洛韦的胃漂浮型给药系统，使用车前子壳和羟丙基甲基纤维素K4M作为聚合物，碳酸氢钠作为产气剂。片剂采用湿法制粒工艺制备。采用3(2)全因子设计优化药物释放曲线。选择车前子壳(X1)和羟丙基甲基纤维素K4M(X2)的用量作为自变量。选择药物溶解50%(t(50%))和70%(t(70%))所需的时间作为因变量。对设计的9批制剂进行硬度、脆碎度、重量差异、药物含量均匀度、溶胀指数、体外漂浮性和体外药物释放曲线评价。所有制剂的漂浮滞后时间均低于3分钟，并在溶出介质中持续漂浮超过24小时。通过设计两个验证点制剂(C1和C2)验证了所建立多项式方程的有效性。t(50%)和t(70%)预测值与实测值的接近程度表明所推导方程对因变量的有效性。这些研究表明，车前子壳和羟丙基甲基纤维素K4M之间的适当平衡可以产生与预测溶出曲线相似的药物溶出曲线。优化后的制剂符合Higuchi动力学，药物释放机制为非Fick扩散，受通过溶胀基质的扩散控制。
