Pentaerythritol as an excipient/solid-dispersion carrier for improved solubility and permeability of ursodeoxycholic acid

Abstract

In this study, the feasibility of using pentaerythritol as a novel excipient/solid-dispersion carrier for enhancing the biopharmaceutical properties of ursodeoxycholic acid (UA) is explored. The solid dispersion formulations of UA were prepared using a solvent evaporation technique. The prepared formulations were evaluated for UA content to assess the UA incorporation efficiency. The formulations were further characterized using photomicroscopy, scanning electron microscopy, particle size analysis, zeta potential analysis, infrared spectroscopy, thermal analysis, x-ray diffractometry, and solubility analysis. The performance of the selected formulation was evaluated by dissolution and permeability studies. A preliminary stability study was performed on the selected formulation. Solid dispersions of UA using pentaerythritol as a carrier were successfully prepared with UA incorporation efficiencies ranging from ~97 to 99 %. The formation of dispersions was supported by instrumental analysis. Compared to pure UA, a 22-fold increase in aqueous solubility of UA was observed in the optimized formulation. The biopharmaceutical characteristics of UA, i.e. the rate and extent of dissolution and permeability, were found to be significantly enhanced in the optimized formulation compared to pure UA. The formulation was also found to be functionally stable for six months when stored in controlled conditions of temperature and humidity. This study shows that pentaerythritol can serve as a potential solid dispersion carrier for active pharmaceutical ingredients (API) and contribute to the enhancement of their biopharmaceutical properties.