奈韦拉平片的制备及溶出度评价

Preparation and in vitro dissolution of nevirapine tablets

目的制备奈韦拉平片并考察其体外溶出度。方法以原料药粒径大小(X1,D50/μm)、填充剂配比(X2)、崩解剂用量(X3,%)为考察因素,以片剂硬度(Y1,N)、奈韦拉平在45 min的溶出度(Y2,%)为片剂考察指标,采用Box-Behnken效应面法优化奈韦拉平片处方;并利用f2相似因子法比较自制制剂和参比制剂的体外溶出相似性。结果奈韦拉平片的最优处方组成为:奈韦拉平原料药的平均粒径(D50)为25μm,填充剂微晶纤维素和一水乳糖比例为1.5∶1、崩解剂用量占片重6.5%,制备的片剂可压性较好、药物能够快速溶出;在4种溶出介质中自制的奈韦拉平片与参比制剂药物体外溶出具有较好的相似性。结论通过Box-Behnken效应面法优化得到的奈韦拉平片处方与参比制剂体外溶出一致性良好,制备工艺可行,有望应用于工业化生产。

Objective To prepare nevirapine tablets and evaluate their in vitro dissolution behaviors. Methods The formulation of nevirapine tablets was optimized by Box-Behnken design response surface methodology. The nevirapine particle size distribution（X1, D50/μm）, the ratio of microcrystalline cellulose to lactose monohydrate（X2）, and amount of disintegration（X3, %） were chosen as independent variables, while tablet hardness（Y1, %）, and nevirapine dissolution at 45 min（Y2, %） were dependent variables. The release rate of nevirapine tablets and that of the reference preparations were compared by f2 similarity factor. Results The optimum formulation of nevirapine tablets was as follows： the nevirapine particle size distribution was 25 μm, the ratio of microcrystalline cellulose to lactose monohydrate was 1.5∶1, and the amount of disintegration was 6.5%. The prepared nevirapine tablets had better compressibility and faster dissolution. The dissolution profile of nevirapine tablets and the reference preparations were similar in different dissolution media. Conclusion The Box-Behnken design response surface methodology is successfully used to optimize the formulation of nevirapine tablets. Nevirapine tablets have good in vitro dissolution consistency with the reference preparations, and it may be used in industrial production.