Improvement of Stability and Dissolution of Prostaglandin E₁ by Maltosyl-β-cyclodextrin in Lyophilized Formulation

Abstract

To improve undesirable pharmaceutical properties of prostaglandin E₁ (PGE₁) in lyophilized formulation, potential use of highly water-soluble maltosyl-β-cyclodextrin (G₂-β-CyD) was examined, comparing it with parent β-cyclodextrin (β-CyD). Inclusion complexation of PGE₁ with G₂-β-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 testd. When the amorphous products were stored at 60°C, decomposition of PGE₁ was significantly decelerated by both G₂-β-CyD and β-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-β-CyD, while it tended to decrease by β-CyD, depending on the moisture-adsorbing and wetting properties along with crystallinity change of the additives. The limited data obtained here suggests that G₂-β-CyD may be preferable to β-CyD for the improvement of chemical instability and poor dissolution properties of PGE₁ in dry solids for injections.