Investigating the Solubilities of the Nitrate and Isomorphous Bromide and Chloride Salts of Dapsone

Abstract

Dapsone, the major drug for leprosy, has broader application against dermatoses, malaria, and AIDS-related diseases. Besides its antimicrobial/ antiprotozoal activity, dapsone has anti-inflammatory properties. However, because of its low aqueous solubility, the high oral doses required and associated side effects limit the tolerability and efficacy of dapsone free base. As a strategy to improve the drug's solubility, new salts of dapsone were prepared. The chloride, bromide, and nitrate salts of dapsone were completely characterized by X-ray diffraction (single and powder), spectroscopic (FT-IR), and thermal (DSC and TGA) techniques. The X-ray results revealed that dapsone chloride and dapsone bromide are isomorphous compounds. Dapsone salts decompose without melting and are thermally less stable than dapsone free base. The equilibrium solubility of dapsone salts was compared to dapsone free base in three aqueous media: HCl buffer pH 1.2, acetate buffer pH 4.5, and phosphate buffer pH 6.8. The highest solubility values were obtained in acid media, and dapsone bromide was found to be slightly more soluble than dapsone free base. The solubility values obtained for the nitrate and chloride salts of dapsone at pH 1.2 cannot be considered real, since the PXRD patterns show their total/partial conversion.