ORIGINAL ARTICLES Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, India Enhancement of dissolution and oral bioavailability of gliquidone with hydroxy propyl-b-cyclodextrin S. Sridevi, A. S. Chauhan, K. B. Chalasani, A. K. Jain, P. V. Diwan Received November 15, 2002, accepted May 5, 2003 Dr. Prakash V. Diwan, Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad – 500 007 A.P., India
[email protected] Pharmazie 58: 807–810 (2003) The virtual insolubility of gliquidone in water results in poor wettability and dissolution characteristics, which may lead to a variation in bioavailability. To improve these characteristics of gliquidone, binary systems with hydroxypropyl-b-cyclodextrin (HP-b-CD) were prepared by classical methods such as physical mixing, kneading, co-evaporation and co-lyophilization. The solid state interaction between the drug and HP-b-CD was assessed by evaluating the binary systems with X-ray diffraction, differen- tial scanning calorimetry and IR- spectroscopy. The results establish the molecular encapsulation and amorphization of gliquidone. The phase solubility profile of gliquidone in aqueous HP-b-CD vehicle À1 resulted in an AL type curve with a stability constant of 1625 M . The dissolution rate of binary sys- tems was greater than that of pure drug and was significantly higher in the case of co-lyophilized and co-evaporated systems. Upon oral administration, [AUC]0-a was significantly higher in case of co-lyo- philized (2 times) and co-evaporated systems (1.5 times) compared to pure drug suspension while other binary systems showed only a marginal improvement. The study ascertained the utility of HP-b- CD in enhancing the oral bioavailability of gliquidone, and points towards a strong influence of the preparation method on the physicochemical properties.