Kim Jeong-Soo, Kim Min-Soo, Park Hee Jun, Lee Sibeum, Park Jeong-Sook, Hwang Sung-Joo
National Research Lab. of Pharmaceutical Technology, College of Pharmacy, Chungnam National University.
Chem Pharm Bull (Tokyo). 2007 Jun;55(6):936-9. doi: 10.1248/cpb.55.936.
The objective of the present study was to evaluate three coating parameters for the application of a blend of HPMCP and HPMC in ethylcellulose aqueous dispersions (Surelease) in order to obtain controlled release of tamsulosin hydrochloride. The selected independent variables, HPMCP content (X1), HPMC content (X2) and coating level (X(3)), were optimized with a three-factor, three-level Box-Behnken design. The selected dependent variables were the cumulative percentage values of tamsulosin hydrochloride that had dissolved after 2, 3 and 5 h. Various dissolution profiles of the drug from controlled release pellets were obtained. Optimization was performed for X1, X2 and X3 using the following target ranges; 15% < or = Y1 < or= 30%; 50% < or = Y2 < or = 65%; 80% < or = Y3 < or = 95%. Results of the optimization procedure indicated that the optimized levels of HPMCP content (X1), HPMC content (X2) and coating level (X3) were 30%, 15% and 25%, respectively. Controlled release pellets coated with the optimized formulation provided a release profile that was close to predicted values. In addition, the dissolution profiles of the controlled release pellets coated with the optimized formulation were similar to those of the commercial product Harunal capsule (f1 = 4.6, f2 = 78.7).
本研究的目的是评估羟丙甲纤维素邻苯二甲酸酯（HPMCP）与羟丙甲纤维素（HPMC）的混合物在乙基纤维素水分散体（Surelease）中的三个包衣参数，以实现盐酸坦索罗辛的控释。通过三因素三水平的Box-Behnken设计对选定的自变量HPMCP含量（X1）、HPMC含量（X2）和包衣水平（X3）进行优化。选定的因变量是盐酸坦索罗辛在2、3和5小时后溶解的累积百分比值。获得了药物从控释微丸的各种溶出曲线。使用以下目标范围对X1、X2和X3进行优化：15%≤Y1≤30%；50%≤Y2≤65%；80%≤Y3≤95%。优化程序的结果表明，HPMCP含量（X1）、HPMC含量（X2）和包衣水平（X3）的优化水平分别为30%、15%和25%。用优化配方包衣的控释微丸提供的释放曲线接近预测值。此外，用优化配方包衣的控释微丸的溶出曲线与市售产品Harunal胶囊的溶出曲线相似（f1 = 4.6，f2 = 78.7）。
