盐酸美金刚缓释片的制备及其体外释放度考察

目的制备盐酸美金刚缓释片,并对其体外释放行为进行考察。方法以HPMC K15M和HPMC K4M为骨架材料压制缓释片。以HPMC(X1)用量和HPMC K15M/K4M用量之比(X2)为考察因素,以盐酸美金刚在2,6和10h的累积释放度Y2h,Y6h,Y10h为考察指标,利用2因素3水平中心复合设计-效应面法优化处方。在4种介质中考察了盐酸美金刚缓释片的体外释药行为。结果最终优化处方中的HPMC用量为片质量的60.0%,HPMCK15M/K4M用量之比为70∶30,所得缓释片在2,6和10h三点的累积释放度符合20%≤Y2h≤30%,40%≤Y6h≤60%和Y10h≥80%的要求,在12h内释放平稳、完全。结论采用中心复合设计-效应面法优化的处方预测性良好,制得的盐酸美金刚缓释片体外释放符合要求。

Preparation of Memantine Hydrochloride Extended-release Tablets and study on its released behavior in vitro

Objective To prepare Memantine Hydrochloride Extended release Tablets, and to investigate its release behavior in vitro. Methods Memantine Hydrochloride Extended-release Tablets were prepared by employing the mixture of HPMC K15M and HPMC K4M as the basic matrix materials. A central composite design-response surface methodology（CCD-RSM） with two factors and three levels was used to optimize the formulation. The HPMC content（X1 ） and HPMC K15M/K4M ratio（X2 ） level were used as two independent factors and the accumulative release amounts at 2,6 and 10 h were used as three dependent variables. In vitro drug release behavior of Memantine Hydrochloride Extended-release Tablets was studied in four different types of release media. Results The optimized formulation contained 60.0% of HPMC in the total tablet weight with the HPMC K15M/ K4M ratio of 70 ： 30. The accumulative release percentages（Y） at 2 ,6 and 10 h were consistent with the criterion of 20%≤Y2 h ≤30%,40%≤Y6 h≤60% ,Y10 h≥80%, respectively. In vitro release data proved that the drug release from the formulation was steady and complete during 12 h. Conclusion The central composite design response surface methodology was successfully used to optimize the formulation of Memantine Hydrochloride Extended release Tablets. The in vitro release profiles of the tablets prepared comply with the guidelines published by the Center for Drug Evaluation, SFDA（CDE）.