Effect of drug loading and relative humidity on the mechanical properties and tableting performance of Celecoxib-PVP/VA 64 amorphous solid dispersions.

ABSTRACT

The mechanical properties of polymer-based amorphous solid dispersions (ASDs) are susceptible to changes in relative humidity (RH) conditions. The purpose of this study is to understand the impact of RH on both the mechanical properties and tableting performance of Celecoxib-polyvinyl pyrrolidone vinyl acetate co-polymer (PVP/VA 64) ASDs. The ASDs were prepared by solvent evaporation technique to obtain films for nanoindentation, which were also pulverized to obtain powder for compaction. Our results show that higher RH corresponds to lower Hardness, H, and Elastic Modulus, E. At a given RH, both the E and H increase with drug loading to a maximum and decrease with further drug loading. Using ASD powders with a narrow particle size range (d50 = 9-14 µm), we have demonstrated that increasing RH from 11% to 67% leads to improved tablet tensile strength for pure PVP/VA 64 and the ASDs. However, the extent of the increase in tablet tensile strength depends on their mechanical properties, H and E, and drug loading. At a higher compaction pressure and a higher RH, the effect of ASD mechanical properties on tabletability is less because the particles are nearly fully deformed so that bonding areas are approximately the same. Thus, difference in tablet strength is mainly contributed by the inter-particulate forces of attraction. Understanding the impact of these key processing conditions, i.e., RH and compaction pressure, will guide the design of an ASD tablet formulation with robust manufacturability.