Combining Two Antitubercular Drugs, Clofazimine and 4-Aminosalicylic Acid, in Order to Improve Clofazimine Aqueous Solubility and 4-Aminosalicylic Acid Thermal Stability

Abstract

Four forms of a salt combining two antitubercular drugs, clofazimine and 4-aminosalicylic acid, are reported and the crystal structure of two of these forms are described. TG/DSC analysis of all four forms demonstrate an increase in the temperature at which degradation (upon decarboxylation) occurs in comparison to pure 4-aminosalicylic acid. Water solubility evaluation indicates a significant increase of the amount of clofazimine detected in water (10.26 ± 0.52 μg/mL for form I, 12.27 ± 0.32 μg/mL for form II, 7.15 ± 0.43 μg/mL for form III and 8.50 ± 1.24 μg/mL for form IV) in comparison to pure clofazimine (0.20 ± 0.03 μg/mL).

Keywords: 4-Aminosalicylic acid; Clofazimine; Differential scanning calorimetry; Polymorph; Salts; Solid-state; Solubility; Thermogravimetric analysis.