(203g) Design and Characterization of Fast-Release Clofazimine Nanoparticles to Improve Bioavailability

Zhang, Y., Princeton University
Feng, J., Princeton University
McManus, S. A., Princeton University
Lu, H. D., Princeton University
Ristroph, K. D., Princeton University
Prud’homme, R. K., Princeton University
Clofazimine is a lipophilic riminophenazine antibiotic recommended by World Health Organization (WHO) as multidrug therapy of leprosy. To improve the drug dissolution rate, clofazimine was encapsulated in nanoparticles prepared with three affordable surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, through the Flash Nanoprecipitation (FNP) process. Lyophilization and spray drying were applied and optimized to solidify nanoparticles. Dissolution tests were carried out to evaluate release profile of clofazimine nanoparticles prepared by different surface coatings in simulated gastric and intestinal fluids, comparing to raw clofazimine powder and commercial product Lamprene®. Remarkably improved dissolution rate and supersaturation levels were observed with all clofazimine nanoparticles despite different release kinetics. In addition, differential scanning calorimetry (DSC) was explored to study the physical state of clofazimine in nanoparticles. The results strongly suggest that the nanoparticles prepared with affordable coatings can be used as viable cryptosporidiosis therapeutics.