Teixeira Maíra T, Sá-Barreto Lívia C L, Gratieri Taís, Gelfuso Guilherme M, Silva Izabel C R, Cunha-Filho Marcílio S S
Laboratory of Food, Drugs and Cosmetics (LTMAC), University of Brasília (UnB), 70910-900, Brasília, DF, Brazil.
Faculty of Ceilândia, University of Brasília (UnB), 72220-900, Brasília, DF, Brazil.
AAPS PharmSciTech. 2017 May;18(4):1393-1401. doi: 10.1208/s12249-016-0615-y. Epub 2016 Sep 1.
Tablet subdivision is a common practice used mainly for dose adjustment. The aim of this study was to investigate how the technical aspects of production as well as the method of tablets subdivision (employing a tablet splitter or a kitchen knife) influence the accuracy of this practice. Five drugs commonly used as subdivided tablets were selected. For each drug, the innovator drug product, a scored-generic and a non-scored generic were investigated totalizing fifteen drug products. Mechanical and physical tests, including image analysis, were performed. Additionally, comparisons were made between tablet subdivision method, score, shape, diluent composition and coating. Image analysis based on surface area was a useful tool as an alternative assay to evaluate the accuracy of tablet subdivision. The tablet splitter demonstrates an advantage relative to a knife as it showed better results in weight loss and friability tests. Oblong, coated and scored tablets had better results after subdivision than round, uncoated and non-scored tablets. The presence of elastic diluents such as starch and dibasic phosphate dehydrate conferred a more appropriate behaviour for the subdivision process than plastic materials such as microcrystalline cellulose and lactose. Finally, differences were observed between generics and their innovator products in all selected drugs with regard the quality control assays in divided tablet, which highlights the necessity of health regulations to consider subdivision performance at least in marketing authorization of generic products.
片剂分割是一种主要用于剂量调整的常见做法。本研究的目的是调查生产的技术方面以及片剂分割方法（使用片剂分割器或菜刀）如何影响这种做法的准确性。选择了五种常用作分割片剂的药物。对于每种药物，研究了创新药物产品、刻痕仿制药和无刻痕仿制药，共计十五种药物产品。进行了包括图像分析在内的机械和物理测试。此外，还对片剂分割方法、刻痕、形状、稀释剂组成和包衣进行了比较。基于表面积的图像分析是评估片剂分割准确性的一种有用的替代检测工具。片剂分割器相对于刀具具有优势，因为它在失重和脆碎度测试中显示出更好的结果。与圆形、未包衣和无刻痕的片剂相比，长方形、包衣和刻痕的片剂在分割后效果更好。淀粉和磷酸二氢钙等弹性稀释剂的存在比分微晶纤维素和乳糖等塑性材料在分割过程中表现出更合适的性能。最后，在所有选定药物的分割片剂质量控制检测方面，观察到仿制药与其创新产品之间存在差异，这突出了健康法规至少在仿制药上市许可中考虑分割性能的必要性。
