Comparative Studies on Solubility and Dissolution Enhancement of Different Itraconazole Salts and Their Complexes

摘要

Itraconazole is a potent triazole antifungal drug which has low solubility at physiological pH conditions. Itraconazole is weakly basic (pKa =3.7) and highly hydrophobic drug. It is categorized as a BCS class II drug. The main objective of the present investigation was to improve the solubility of itraconazole, by preparation of salt forms itraconazole hydrochloride, mesylate and besylate by using addition reaction with hydrochloric acid, methane sulphonic acid and benzene sulphonic acid. Further inclusion complexes of itraconazole were prepared with Captisol (sulfobutyl ether_(7) β-cyclodextrin) by using physical mixing, kneading and co-evaporation techniques. The preparations were characterized by using X-ray diffraction, Fourier Transformed Infrared spectroscopy and Nuclear Magnetic Resonance spectroscopy. The solubility of prepared salt was found multifold than the solubility of itraconazole. The dissolution studies exhibited higher percentage drug dissolution from itraconazole complexes than that of the pure drug which can be attributed to the increase in drug solubility provoked by the complexation technique.