Gong Xingchu, Sun Changquan Calvin
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA.
Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA.
Eur J Pharm Biopharm. 2015 Jun;93:260-6. doi: 10.1016/j.ejpb.2015.04.007. Epub 2015 Apr 20.
Brittleness is one of the important material properties that influences the success or failure of powder compaction. We have discovered that the reciprocal of diametrical elastic strain at fracture is the most suitable tablet brittleness indices (TBIs) for quantifying brittleness of pharmaceutical tablets. The new strain based TBI is supported by both theoretical considerations and a systematic statistical analysis of friability data. It is sufficiently sensitive to changes in both tablet compositions and compaction parameters. For all tested materials, it correctly shows that tablet brittleness increases with increasing tablet porosity for the same powder. In addition, TBI increases with increasing content of a brittle excipient, lactose monohydrate, in the mixtures with a plastic excipient, microcrystalline cellulose. A probability map for achieving less than 1% tablet friability at various combinations of tablet tensile strength and TBI was constructed. Data from marketed tablets validate this probability map and a TBI value of 150 is recommended as the upper limit for pharmaceutical tablets. This TBI can be calculated from the data routinely obtained during tablet diametrical breaking test, which is commonly performed for assessing tablet mechanical strength. Therefore, it is ready for adoption for quantifying tablet brittleness to guide tablet formulation development since it does not require additional experimental work.
脆性是影响粉末压片成败的重要材料特性之一。我们发现，断裂时直径方向弹性应变的倒数是用于量化药物片剂脆性的最合适的片剂脆性指数（TBI）。基于应变的新TBI得到了理论考量以及脆碎度数据的系统统计分析的支持。它对片剂组成和压片参数的变化都足够敏感。对于所有测试材料，它正确地表明，对于相同的粉末，片剂脆性随片剂孔隙率的增加而增加。此外，在与塑性辅料微晶纤维素的混合物中，TBI随脆性辅料一水乳糖含量的增加而增加。构建了在片剂拉伸强度和TBI的各种组合下实现片剂脆碎度小于1%的概率图。市售片剂的数据验证了该概率图，建议将TBI值150作为药物片剂的上限。该TBI可以从片剂直径断裂试验过程中常规获得的数据计算得出，片剂直径断裂试验通常用于评估片剂机械强度。因此，它无需额外的实验工作即可用于量化片剂脆性以指导片剂配方开发。
