Influence of the drug deformation behaviour on the predictability of compressibility and compactibility of binary...

Various studies investigate the predictability of the compressibility and compactibility of tablet formulations based on the behaviour of the pure materials. However, these studies are limited to a few materials so far probably because of the complexity of the powder compaction process. One approach preventing the excessive increase in complexity is the extension of the investigations from pure materials to binary powder mixtures. The focus of this study is on the predictability of the compressibility and compactibility of binary mixtures consisting of an active pharmaceutical ingredient (API) and the excipient microcrystalline cellulose. Three APIs with markedly different deformation behaviour were used. The API concentration and type are systematically varied. For all three material combinations it is found that the in-die compressibility of the binary mixtures can be precisely predicted based on the characteristic compression parameters of the raw materials using the extended in-die compression function in combination with a volume-based linear mixing rule. Since the tablet porosity (out-of-die) also follows a linear mixing rule, the predictability can be further extended using the method of Katz et al. In contrast, the influence of the API concentration on compactibility or rather on tablet tensile strength is non-linear and strongly dependent on the deformation behaviour of the API, making the predictability more difficult. Neither the approach of Reynolds et al. nor this of Kuentz and Leuenberger are able to predict the compactibility when clear deviations from a linear mixing rule appear.