title: A new tablet brittleness index.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xingchu
authors.initials: X
authors.lastname: Gong
authors.affiliation: Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA. Electronic address: sunx0053@umn.edu.
authors.forename: Changquan Calvin
authors.initials: CC
authors.lastname: Sun
mesh_terms: D001499:Bayes Theorem; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D004548:Elasticity; D005079:Excipients / Q000737:chemistry; D006244:Hardness; D006245:Hardness Tests; D007785:Lactose / Q000737:chemistry; D008956:Models, Chemical; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders; D011312:Pressure; D015203:Reproducibility of Results; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013718:Tensile Strength
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D011208:Powders; D013607:Tablets; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose
keywords: Brittleness; Elastic deformation; Friability; Powder technology; Strain; Tablet