Bioavailability Enhancement of Poorly Water Soluble and Weakly Acidic New Chemical Entity with 2-Hydroxy Propyl-β-Cyclodextrin: Selection of Meglumine, a Polyhydroxy Base, as a Novel Ternary Component

The purpose of the present study was to investigate the influence of a polyhydroxy base, N-acetyl glucamine (also know as Meglumine), as a ternary component on the complexation of DRF-4367, a poorly water-soluble and weakly acidic anti-inflammatory molecule, with 2-hydroxypropyl-β-cyclodextrin (HPβCD). The molecular inclusion of DRF-4367 with HPβCD alone and in combination with ternary component was aimed at improvement in solubility and, subsequently, dissolution rate-limited oral bioavailability. The solid complexes of DRF-4367 and HPβCD with or without meglumine (binary and ternary systems, respectively) were prepared as coevaporated product in different stoichiometric ratios and compared against physical mixture. The formation of inclusion complexes was confirmed by using classical instrumental techniques. Phase solubility studies suggested that meglumine was responsible for solubility improvement via multiple factors rather than just providing a favorable pH. Mechanisms and factors governing solubili...