Preparation method for solubilizing poorly oil-soluble compound in oil phase and the sustained release characteristics after subcutaneous administration in rats

Abstract

The aim of this study was to develop a simple preparation method for solubilizing poorly oil-soluble compound in oil phase and evaluate the sustained release characteristics of the oil-based formulation in rats. A pharmaceutical approach for solubilizing hydrophilic compounds (methylene blue and fluorescein sodium) into oil phase using propylene glycol (PG) as a water-soluble phase was carried out. From the investigation of oily solvents which prevented anti-solvent phenomenon occurring by the mixture of PG and oil, it was clear that triacetin was preferable as the third ingredient. Namely, regardless of ratio makeup, solutions comprising fatty acid, triacetin, and PG were useful for dissolving poorly oil-soluble compounds. Three formulations dissolving raloxifene hydrochloride (RXF), i.e., PG solution (Rp-1), water-in-oil (w/o) emulsion (Rp-2), and oleic acid/triacetin/PG (1:1:2, v/v/v) (Rp-3) were prepared in order to estimate the sustained release characteristics in rats. The eliminated amount of RXF into bile until 72 h after the subcutaneous administration of Rp-3 was one-ninth of that by Rp-1 and one-fifth of that by Rp-2, and the residual amount of RXF in the subdermal site after the administration of Rp-3 was 2.5-3.3-folds that by Rp-1 and 1.5-1.6-folds of that by Rp-2. These results suggested that the mixture of fatty acid/triacetin/PG is simple and stable for the preparation, and is remarkably useful as a sustained release formulation.