IMPROVEMENT OF STABILITY AND DISSOLUTION OF PROSTAGLANDIN-E(1) BY MALTOSYL-BETA-CYCLODEXTRIN IN LYOPHILIZED FORMULATION

To improve undesirable pharmaceutical properties of prostaglandin E1 (PGE1) in lyophilized formulation, potential use of highly water-soluble maltosyl-beta-cyclodextrin (G2-beta-CyD) was examined, comparing it with parent beta-cyclodextrin (beta-CyD). Inclusion complexation of PGE1 with G2-beta-CyD in an aqueous solution was estimated by the solubility method, circular dichroism and carbon-13 nuclear magnetic resonance spectroscopies. PGE1 was freeze-dried with various additives and subjected to stability and dissolution tests. When the amorphous products were stored at 60-degrees-C, decomposition of PGE1 was significantly decelerated by both G2-beta-CyD and beta-CyD, while it was accelerated by mannitol as an inert ingredient. During storage, the rapid dissolving property of PGE1 was maintained by complexation with G2-beta-CyD, while it tended to decrease by beta-CyD, depending on the moisture-adsorbing and wetting properties along with crystallinity change of the additives. The limited data obtained here suggests that G2-beta-CyD may be preferable to beta-CyD for the improvement of chemical instability and poor dissolution properties of PGE1 in dry solids for injections.