Composing Novel Diclofenac Potassium and l-Proline Salt Cocrystal as a Strategy to Increase Solubility and Dissolution

Abstract

This research dealt with the multicomponent crystal developed from diclofenac potassium and l-proline to improve the pharmaceutical performance of this anti-inflammatory drug. Slow evaporation of the component mixture at a 1:1 M ratio, supported by ultrasonication, yielded a new salt cocrystal, which was characterized using thermal analysis, Karl Fischer titration, infrared spectrophotometry, powder diffractometry, and single crystal diffractometry. This salt cocrystal was confirmed as a tetrahydrate that comprised diclofenac potassium, l-proline, and water (1:1:4), named DKPH. The new salt cocrystal enhanced the solubility of diclofenac potassium by up to 3.56 folds and accelerated the intrinsic dissolution rate of 3.36 folds. It was supported by the solid and solution phase intermolecular interaction study. A different phase, which indicated a monohydrate form of the salt cocrystal, was found from the low humidity chamber during the isotherm sorption study. However, the tetrahydrate, DKPH, was proven as a stable form under ambient conditions.

Keywords: Diclofenac potassium; Hydrate; Intrinsic dissolution; Multicomponent; Pseudo polymorph; Salt cocrystal; Solubility; Solute–solute interaction; Stability; l-proline.