A compression behavior classification system of pharmaceutical powders for accelerating direct compression tablet formulation design

Abstract

In this paper, a compression behavior classification system (CBCS) for direct compression (DC) pharmaceutical powders is presented. Seven descriptors from a series of compression models for powder compressibility, compactibility and tabletability analysis were included in the CBCS. A new tabletability index d was proposed to differentiate three categories of tensile strength (TS) vs. pressure relationships, and its physical meaning was explained thoroughly. 130 materials containing diverse pharmaceutical excipients and natural product powders (NPPs) were fully characterized and were compiled into an in-house developed material library, in which 70 materials with potential DC applications were used to justify the effectiveness of the CBCS. Principle component analysis (PCA) was used to uncover the latent structure of compression variables. Moreover, partial least squares (PLS) regression models are established in prediction of both tablet TS and solid fraction (SF) based on the raw materials' physical characteristics, the compression behavior indices and the compression force. The obtained scores and loadings are used to group the materials and the compression variables, respectively. Different categories of tabletability for DC powders were clearly clustered along two orthogonal directions pointing to the index d and the compression force. Finally, a multi-objective design space was identified under the latent variable space, summarizing the operationally possible region for both material properties and compression pressure required in DC tablet formulation design.

Keywords: Compactibility; Compressibility; Compression behavior classification system (CBCS); Design space; Formulation design; Tabletability.