RijksInstituut voor Volksgezondheid en Milieu RIVM (National Institute for Public Health and the Environment), Bilthoven, The Netherlands.
AAPS PharmSciTech. 2010 Mar;11(1):126-32. doi: 10.1208/s12249-009-9365-4. Epub 2010 Jan 15.
At present, the ease of subdivision of scored tablets is estimated in vivo. In order to replace such in vivo testing and to develop a surrogate test which uses in vitro techniques, the association between physical parameters of scored tablets and their ease of subdivision was studied. The physical properties of 23 brands of scored tablets of which their ease of subdivision in vivo was known were established. Statistical modeling using a logistic regression model was used to fit the data and estimate the contribution of each physical parameter to the goodness of the fit. For scored oblong tablets, the critical parameters for their ease of subdivision are: diameter; diameter/width ratio; depth of score line and resistance to crushing. Criteria for each of these parameters were derived. All criteria need to be complied with to guarantee sufficient ease of subdivision of scored oblong tablets. For scored round tablets the critical parameters, in decreasing order of importance, for their ease of subdivision, are: resistance to crushing, diameter, score mark (one- or two-sided), and shape (flat or biconvex). A five-parameter predictive model was developed, showing excellent discrimination. For development, the proposed surrogate tests are sufficiently reliable. For release testing and stability studies, resistance to crushing of a scored tablet is a reliable predictor of its ease of subdivision.
目前，评估刻痕片剂的易分割性是在体内进行的。为了替代这种体内测试并开发一种使用体外技术的替代测试，研究了刻痕片剂的物理参数与其易分割性之间的关系。确定了 23 个已知体内易分割性的刻痕片剂品牌的物理特性。使用逻辑回归模型进行统计建模来拟合数据，并估计每个物理参数对拟合优度的贡献。对于刻痕长形片剂，其易分割性的关键参数是：直径；直径/宽度比；刻痕线的深度和抗压强度。推导出了这些参数的标准。为了保证刻痕长形片剂有足够的易分割性，所有标准都需要符合。对于刻痕圆形片剂，其易分割性的关键参数（按重要性降序排列）为：抗压强度、直径、刻痕标记（单面或双面）和形状（平或双凸）。开发了一个五参数预测模型，显示出极好的区分能力。对于开发，所提出的替代测试足够可靠。对于放行测试和稳定性研究，刻痕片剂的抗压强度是其易分割性的可靠预测指标。
