Analytical method development for powder characterization: Visualization of the critical drug loading affecting the processability of a formulation for direct compression

摘要

Characterization of particulate systems (powders) is one of the remaining scientific challenges. Evaluation of powder behaviour is often empirical and the decision-making processes are experience-based. There is a need for development of analytical instrumentation enabling more fundamental understanding of powder behaviour. Flowability and tabletability, two key factors in commercial scale manufacturing of tablets with direct compression (DC) approach, were analysed for formulations containing increasing amounts of several model active pharmaceutical ingredients (APIs). Flowability was investigated using a ring shear tester and tablets were prepared at four different compression pressures using a single punch tablet press. Thereby, a material sparing screening approach was developed to estimate the influence of APIs on behaviour of a given DC formulation. Additionally, this approach is useful for estimating the low threshold amount of API (wt%), at which the properties of an API start affecting the powder behaviour of a given formulation (API-excipient mixture). This threshold will be referred to as critical drug loading. The flowability of microcrystalline cellulose (reference grade pH 102) was used as a threshold for adequate flowability of model formulations. The threshold for tablet tensile strength was set to 2 MPa.