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

Abstract 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.