To study physical compatibility between dibasic calcium phosphate and cohesive actives using powder rheometer and thermal methods

Abstract

Aim: An attempt is made to provide better understanding of the compatibility aspect of excipients with different properties of active pharmaceutical ingredient (API) using various rheological, thermal and morphological studies conducted on binary mixtures of Dibasic Calcium Phosphate anhydrous (DCP-A) and Dibasic Calcium Phosphate dihydrate (DCP-D) forms with cohesive API’s (Acetaminophen and Aspirin).

Method: Binary mixtures of DCP’s were prepared by addition of 0% w/w to 50% w/w of the API in each powder blend. Powder rheological analysis were conducted using FT4 powder rheometer, rotational shear cell and empirical approaches such as angle of repose (AOR), Hausner ratio (HR) and Carr’s index (CI). Thermal analysis was conducted using differential scanning calorimetry (DSC) and thermal effusivity. Morphological studies were conducted using Scanning Electron Microscopy (SEM) to determine the fundamental differences between powder materials.

Result/Conclusions: Powder rheometer showed distinctive understanding in the flowability behavior of binary mixtures with addition of increasing proportion of API’s than empirical approaches. Thermal approaches revealed the potential interaction of water of crystallization DCP-D while such interaction was absent in DCP-A. Binary mixtures prepared using DCP-D were better flowable while blends containing DCP-A were better in stability (physical), compressibility and permeability. This study allows the scientist to understand the powder packing of different blends with their flowability and compressibility parameter and helps selection of appropriate form of hydrate for relevant API.

• Cohesive powder
• compatibility
• effusivity
• flowability
• hydrates
• powder rheology

Acknowledgements

The authors would like to thank International Pharmaceutical Excipients Council for graduate student support.