Formulation of Diacerein Cocrystal Using β-Resorcylic Acid for Improvement of Physicomechanical and Biopharmaceutical Properties

Abstract

Diacerein (DIA) is an approved treatment for osteoarthritis. However, its clinical effectiveness is limited because of its poor aqueous solubility, which causes bioavailability issues. The current study aimed to augment the functionality of DIA using a cocrystallization approach. A newly developed cocrystal of DIA with β-resorcylic acid (RA) was produced at different ratios via the antisolvent crystallization technique. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform IR (FT-IR) spectroscopy, and scanning electron microscopy (SEM) were carried out to investigate the formation of the cocrystals. The cocrystallized samples were further evaluated for their biopharmaceutical properties. The DSC study demonstrated a “W”-type phase diagram with a sharp endothermic event at a DIA:RA molar ratio of 1:3. A distinct PXRD pattern at the optimized ratio confirmed the formation of a novel cocrystal, and this was confirmed using FT-IR analysis. SEM analysis revealed the topographical variation of the prepared cocrystal, suggesting the generation of a new solid phase. Physicomechanical properties such as apparent solubility, dissolution, packability, compressibility, compactibility, and stability exhibited the improved functionality of the prepared cocrystal compared with pure DIA. Significant enhancement of bioavailability (3.2-fold) was observed for the prepared cocrystal relative to DIA alone. Hence, the fast dissolving capability and improved tabletability and bioavailability of the DIA−RA cocrystal make it a more favorable candidate for better dosage form development.