(776f) Size Reduction through Flash Nanoprecipitation to Improve Solubility, Dissolution, and Bioavailability of Clofazimine

Authors: 
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 poorly soluble riminophenazine antibiotic (logP= 7.66) approved by Food and Drug Administration (FDA) with good safety record. Thus, a reliable, efficacious, and fast-release formulation of clofazimine is highly desired. To improve the drug bioavailability and dissolution rate, clofazimine was encapsulated in nanoparticles prepared with three different surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, through the Flash Nanoprecipitation (FNP) process with high encapsulation efficiency. To convert liquid colloidal suspensions to powders, lyophilization and spray drying, were applied to solidify nanoparticles. Dissolution tests were carried out to evaluate release kinetics of clofazimine nanoparticles prepared by different surface coatings, comparing to raw clofazimine powder and its currently market product Lamprene®. Remarkably improved dissolution rate and supersaturation levels were observed with all clofazimine nanoparticles despite different release kinetics. Additionally, calorimetry technique was explored to study the crystallinity of clofazimine in nanoparticles. The results strongly suggest that the new clofazimine nanoparticles prepared with affordable materials can be used as viable cryptosporidiosis therapeutics.
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