Use of Proteins to Increase the Aqueous Solubility of Rifapentine

Abstract

Parenteral formulations of the poorly soluble antituberculosis antibiotic rifapentine were developed. Proteins (human serum albumin, succinylated gelatin, and sodium caseinate) were used to produce water-soluble forms of rifapentine by precipitation or homogenization. Ultrasonic homogenization gave the best results, i.e., stable colloidal suspensions with 9 – 10 mg of rifapentine per mL (practically 100 times greater than its water solubility). Dilution of the suspensions led to dissociation of the aggregates formed during the solubilization and formation of a clear solution. The particle size decreased to 10 – 20 nm, which corresponded to the particle size in a solution of the proteins at the same concentration. This would not cause embolization upon infusion of such water-soluble forms of rifapentine. The results indicated that the selected approach was promising for designing parenteral formulations of rifapentine.