D-最优混料试验设计法优化阿德福韦酯片处方  

Formula Optimization of Adefovir Dipivoxil Tablets by D-optimal Mixture Design

作　　者：张春燕[1] 赵迎春[1] 范义凤[1] 

机构地区：[1]南通大学附属医院药学部,江苏南通226001

出　　处：《中国药师》2017年第12期2160-2164,共5页China Pharmacist

摘　　要：目的:优化阿德福韦酯片处方,并考察其体外溶出度。方法:以填充剂用量(X_1,%)、崩解剂用量(X_2,%)和黏合剂用量(X_3,%)为影响因素,以脆碎度(Y_1,%)、崩解时限(Y_2,min)、阿德福韦酯30 min溶出度(Y_3,%)为评价指标,采用D-最优混料试验设计法对阿德福韦酯片处方进行优化;采用f_2相似因子法比较阿德福韦酯片仿制制剂和参比制剂的体外溶出行为相似性;通过高温、高湿、光照试验初步评价仿制制剂的稳定性。结果:阿德福韦酯片的最优处方组成为:填充剂一水乳糖用量占片重67.0%、崩解剂交联羧甲基纤维素钠占片重8.0%,黏合剂预胶化淀粉占片重12.0%,制备的片剂脆碎度较低、崩解时限较短、药物溶出度高。阿德福韦酯片仿制制剂和参比制剂在4种溶出介质中的溶出相似因子f_2均大于50。影响因素试验结果要求本品应防潮保存。结论:通过D-最优混料试验设计法优化得到的阿德福韦酯片处方与参比制剂体外溶出一致性良好,制备工艺可行,能够满足制剂大生产的要求。Objective： To optimize the formula of adefovir dipivoxil tablets and investigate the dissolution in vitro. Methods： The formula was optimized by the D-optimal mixture design, the effects of the amount of filler （X1, % ）, the amount of disintegrant agent （ X2, % ） and the amount of binder （X3, % ） were selected as the independent variables, and the friability （ Y1, % ）, disintegration time （ Y2, min） and dissolution of adefovir dipivoxil （ Y3, % ） were the dependent variables. The similarity of the serf-prepared prepa- ration and the reference preparation was obtained by using f2 similarity factor. The stability of adefovir dipivoxil tablets was evaluated preliminarily by high temperature, high humidity and strong light testing. Results： The optimal formula of adefovir dipivoxil tablets was as follows ： the amount of lactose monohydrate was 67.0%, the weight of croscarmellose sodium was 8.0% and the amount of pregelati- nized starch was 12.0%. The prepared tablets had lower friability, shorter disintegration time and higher drug dissolution rate. The dissolution similarity factors of the serf-prepared tablets and the reference preparation in four dissolution media were all greater than 50. The results of influencing factor tests showed that the product should be moisture preservation. Conclusion： The formula of adefovir dip- ivoxil tablets optimized by the D-optimal mixture design is similar to that of the reference preparation, and the preparation process is feasible, which can meet the requirements of large production.

关 键 词：阿德福韦酯片 D-最优混料试验设计法 脆碎度 崩解时限 溶出度 

分 类 号：R944.4[医药卫生—药剂学]