Preformulation studies to guide the development of raloxifene lipid-based delivery systems

Abstract

This study sought to evaluate raloxifene hydrochloride (RLX) solubility and compatibility with lipid excipients (oils, water-soluble and water-insoluble surfactants) with a view of assisting in the proper choice of excipients in the development of lipid-based drug delivery systems. Drug–lipid excipient compatibility was studied using thermal analysis (differential scanning calorimetry and thermogravimetry), and isothermal stress testing (IST) with a validated HPLC method. Drug solubility was determined using equilibrium solubility and pharmacopoeial methods. Among the eleven studied excipients, sunflower oil and soy lecithin presented clear signs of thermal interaction and reduction in the stability of RLX, while mixtures containing emulium® 22 showed a significant reduction in drug content. These three materials were considered incompatible with RLX. The solubility study revealed that RLX has higher solubility in castor oil and in its derivative, polyethoxylated castor oil. Plurol Isostearique® showed the best result among the water-insoluble surfactants. Thermal analysis associated with accelerated IST studies and together with solubility determinations have been shown to be a valuable strategy for the development of lipid-based drug delivery systems containing RLX.