Solubilization and preformulation studies on PG-300995 (an anti-HIV drug)

This study investigates the solubilization of a potential anti-human immunodeficiency virus agent [PG-300995 or 2-(2-thiophenyl)-4-azabenzoimidazole] for oral administration. The intrinsic solubility of PG-300995 is 51 μg/mL. Multiple approaches including combinations of pH control and cosolvency, micellization, or complexation were used to improve the solubility of PG-300995. The combined techniques increased the solubility of both the unionized and ionized species. The solubility of the drug increased from 20 to 200 times depending on the pH and concentration of solubilization agents. The following formulations which contain the desired doses of 5 and 10 mg/mL were developed for oral administration. Formulation A: 10 mg/mL PG-300995 in 20% sulfobutyl ether-β-cyclodextrin at pH 2; formulations B: 5 mg/mL PG-300995 in 10% sulfobutyl ether-β-cyclodextrin at pH 2; formulation C: 5 mg/mL PG-300995 in 10% ethanol+40% propylene glycol at pH 2. No precipitation was observed after series dilution of these three formulations with water or pH 2 buffers. These formulations are stable for at least 6 months after storing at room temperature and 37°C.