Shailesh Tp, Vipul Pd, Girishbhai Jk, Manish Cj
Department of Pharmaceutics and Pharmaceutical Technology, Shri Sarvajanik Pharmacy College, Mehsana - 384 001, Gujarat, India.
J Young Pharm. 2010 Jan;2(1):27-34. doi: 10.4103/0975-1483.62209.
The aim of the present investigation was to develop sustained release ethylcellulose-coated egg albumin microspheres of diltiazem hydrochloride (DH) to improve patient compliance. The microspheres were prepared by the w/o emulsion thermal cross-linking method using different proportion of the polymer to drug ratio (1.0:1.0, 1.0:1.5 and 1.0:2.0). A 3(2) full factorial design was employed to optimize two independent variables, polymer to drug ratio (X(1)) and surfactant concentration (X(2)) on dependent variables, namely % drug loading, % drug release in 60 min (Y(60)) and the time required for 80 % drug release (t(80)) were selected as dependable variable. Optimized formulation was compared to its sustained release tablet available in market. The polymer to drug ratio was optimized to 1:1 at which a high drug entrapment efficiency 79.20% ± 0.7% and the geometric mean diameter 47.30 ± 1.5 mm were found. All batches showed a biphasic release pattern; initial burst release effect (55% DH in 1 h) and then were released completely within 6 h. In situ coating of optimized egg albumin DH microspheres using 7.5% ethylcellulose significantly reduced the burst effect and provided a slow release of DH for 8-10 h. Finally, it was concluded that ethylcellulose-coated egg albumin DH microspheres is suitable for oral SR devices in the treatment of angina pectoris, cardiac arrhythmias, and hypertension due to their size and release profile.
本研究的目的是开发盐酸地尔硫䓬（DH）的乙基纤维素包衣白蛋白微球缓释制剂，以提高患者的依从性。采用油包水乳液热交联法，以不同聚合物与药物比例（1.0:1.0、1.0:1.5和1.0:2.0）制备微球。采用3（2）全因子设计优化两个自变量，即聚合物与药物比例（X(1)）和表面活性剂浓度（X(2)）对因变量的影响，选取药物载量百分比、60分钟时的药物释放百分比（Y(60)）以及80%药物释放所需时间（t(80)）作为因变量。将优化后的制剂与市售缓释片进行比较。聚合物与药物比例优化为1:1时，药物包封率高达79.20%±0.7%，几何平均直径为47.30±1.5mm。所有批次均呈现双相释放模式；初始有突释效应（1小时内释放55%的DH），然后在6小时内完全释放。使用7.5%乙基纤维素对优化后的白蛋白DH微球进行原位包衣，显著降低了突释效应，并使DH缓释8 - 10小时。最后得出结论，乙基纤维素包衣白蛋白DH微球因其尺寸和释放特性，适用于口服缓释装置，用于治疗心绞痛、心律失常和高血压。
