Effect of Co-Crystallization on Physicochemical and Pharmacokinetic Properties of Rifaximin

Rifaximin, a semi-synthetic derivative of rifamycin is a BCS class IV drug having poor physicochemical properties. These poor physicochemical properties pose a major challenge in dosage form production and limited bioavailability restricts the systemic use of rifaximin. This study focuses on the improvement of physicochemical properties and in-vivo bioavailability of rifaximin by utilizing co-crystallization approach. Co-crystallization of rifaximin with l-proline (amino acid) resulted in improvement of physicochemical properties like saturation solubility, dissolution rate, flow-ability, and 1.5-fold improvement in anti-microbial activity as compared to pure rifaximin. Ex-vivo permeation rate was improved approximately two-fold and in an in-vivo study utilizing Sprague Dawley rats, relative bioavailability was estimated to be 785.5967 +/- 55.8986. The data suggest exponential improvement of both, physicochemical properties and bioavailability in the co-crystallized form of rifaximin. This study might be a first step for the use of rifaximin in systemic infections and may open a path for rifaximin as a drug of choice for various bacterial infections.