奥卡西平半片制剂的往复筒溶出方法研究及分剂量评价

Study on Oxcarbazepine Half-tablet Preparation by Reciprocating Cylinder Method and Partial Dose Evaluation

关键词:  奥卡西平  刻痕片  往复筒法  溶出曲线  分剂量

Key words:  oxcarbazepine  scored tablet  reciprocating cylinder method  dissolution curve  dosage segmentation

摘要:

目的 建立往复筒溶出方法考察奥卡西平刻痕片仿制药与原研药分割后半片制剂的体外溶出行为相似性，评价原研药和仿制药的分剂量药学特性差异。方法 以pH 1.2盐酸溶液、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液和水(均含0.5%十二烷基硫酸钠250 mL)为溶出介质，往复频率为10 dip·min^-1，采用往复筒溶出装置测定仿制药和原研药的溶出曲线，结合相似因子(f₂)法评价仿制药和原研药的溶出行为相似性，并与桨法进行比较。采用脆碎度检测仪及电子天平，通过人工掰分法和切药器法测定各厂家半片制剂的脆碎度、分割后质量差异及质量损失。结果 仿制药A在4种溶出介质中的f₂均>50，与原研药的溶出行为相似；仿制药B在4种溶出介质中f₂均<50，和原研药的溶出行为不相似。仿制药A、B分割后质量差异、质量损失和脆碎度均高于原研药。结论 采用往复筒法测定奥卡西平半片制剂的溶出曲线相较于桨法具有良好的区分力，且仿制药的分剂量质量控制相较于原研药仍有一定差距。

Abstract:

OBJECTIVE To establish a reciprocating tube dissolution method to investigate the similarity of in vitro dissolution behavior of oxcarbazepine scored tablet preparations between the original and generic drugs, and to evaluate the differences in dose-specific pharmaceutical properties between the original and generic drugs. METHODS Using 250 mL of pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer, and water(all 0.5% sodium dodecyl sulfate) as the dissolution medium, and reciprocating frequency of 10 dip min^-1, using a reciprocating tube dissolution device to determine the dissolution curves of generic drugs and original research drugs, and combining the similarity factor(f₂) method to evaluate the similarity of dissolution behavior between generic drugs and original research drugs, and compared the result with paddle method. The friability, weight variation and loss of mass of half-tablets were determined by friability tester and electronic balance through splitting by hand and by the cutting device respectively. RESULTS The f₂ of generic drug A in 4 dissolution medium were higher than 50 and showed its similarity to original drug. While the generic drug B was not consistent with the dissolution behavior of original drug as its f₂ factorswere all less than 50 in 4 dissolution. The post-segmentation weight variation, loss of mass and fragility of generic drug A and B were higher than those of the original drug. CONCLUSION The dissolution curve of oxcarbazepine half tablet preparation measured by the reciprocating cylinder method has good discrimination compared to the paddle method, and there is still a certain gap in the quality control of the generic drug in different doses compared to the original research drug.