Abstract
The aqueous solubility of cyclosporin (CYA) was remarkably increased by the 2, 6-di-methyl-α-cyclodextrin (DM-α-CD) complex, forming a higher order complex. Analysis of the phase solubility diagram at 37°C estimated the stoichiometric ratio of the main complex to be 1: 3 (CYA: DM-α-CD) with a stability constant of 18600M-1. Kneading mixtures of CYA with DM-α-CD in various molar ratios (1: 3 to 1: 200) were prepared. The effects of DM-α-CD on the gastrointestinal absorption of CYA was then investigated in the rat. The mean absorption time and the mean residence time of CYA was shortened with the increase in the molar ratio of DM-α-CD to CYA. The maximal AUC was obtained after the administration of the 1: 30 kneading mixture. A further increase in the molar ratio of DM-α-CD showed insignificant changes with regard to the extent of bioavailability. The bioavailability of each mixture was almost the same as or slightly higher than that of Sandimmun®.
