Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-aini street, Cairo 11562, Egypt.
Int J Pharm. 2011 Feb 28;405(1-2):102-12. doi: 10.1016/j.ijpharm.2010.12.003. Epub 2010 Dec 9.
A controlled release resinate beads of betahistine diHCl (BHCl), a short half-life freely water soluble drug, was developed to allow once-daily administration to improve patient compliance and eliminate the risk of intolerance of the drug. BHCl-resin complex was subsequently coated with Eudragit RS100. A 2(4) full factorial design was employed for optimization and to explore the effect of Eudragit RS100 concentration in the coating solution (X(1)), the coating percentage (X(2)), the speed of rotation (X(3)) and the concentration of plasticizer (PEG 400) (X(4)) on the release rate of the drug from the microcapsules. The extent of coating (Y(1)), and the percentage drug released at given times (Y(2), Y(3) and Y(4)) were selected as dependent variables. The optimization process was performed for X(1), X(2), X(3) and X(4) using target ranges of these responses determined based on target release model deduced form zero-order dissolution profile of BHCl for once-daily administration. The levels of X(1), X(2), X(3) and X(4) of optimized BHCl microcapsules are 14.42%, 50.63%, 1495rpm and 9.94%, respectively. The calculated value of f(2) for the optimized BHCl microcapsules filled into hard gelatin capsules was 67.03 indicating that the dissolution profiles of the optimized formulation is comparable to that of the target release model. It could be concluded that a promising once-daily extended-release microcapsules of the highly water soluble drug, BHCl, was successfully designed.
盐酸倍他司汀（BHCl）是一种半衰期短、水溶性好的药物，为了实现每日给药一次以提高患者顺应性并消除药物不耐受的风险，我们开发了一种控制释放的树脂珠。BHCl-树脂复合物随后用 Eudragit RS100 包衣。采用 2(4)完全因子设计进行优化，并考察了包衣液中 Eudragit RS100 浓度（X(1)）、包衣百分比（X(2)）、旋转速度（X(3)）和增塑剂（PEG 400）浓度（X(4)）对药物从微囊中释放速率的影响。包衣程度（Y(1)）和给定时间的药物释放百分比（Y(2)、Y(3)和 Y(4)）被选为因变量。根据基于 BHCl 零级溶出曲线推导的每日一次给药的目标释放模型，确定了这些响应的目标范围，然后对 X(1)、X(2)、X(3)和 X(4)进行优化。优化后 BHCl 微胶囊的 X(1)、X(2)、X(3)和 X(4)水平分别为 14.42%、50.63%、1495rpm 和 9.94%。填充到硬明胶胶囊中的优化 BHCl 微胶囊的计算 f(2)值为 67.03，表明优化配方的溶出曲线与目标释放模型相当。可以得出结论，成功设计了一种有前途的高水溶性药物盐酸倍他司汀每日一次的延长释放微胶囊。
