A less irritant norcantharidin lipid microspheres: Formulation and drug distribution

Abstract

Lipid microspheres (LM) have recently been used as intravenous (i.v.) carriers for drugs, which are sufficiently soluble in oil. However, in the case of norcantharidin (NCTD), which is poorly soluble in both the water and oil phases, this approach is not feasible. In this study, NCTD-loaded LM was prepared by transferring the drug to the interfacial surface of the oil and aqueous phases to produce a less irritating i.v. formulation of NCTD. A probe type sonicator was used to disperse NCTD into the oil phase together with lecithin and Tween 80. A high-pressure homogenization process was used to prepare the lipid microspheres and localize the drug at the surfactant layer. The LM loaded with NCTD consisted of 0.02% drug. Characterization of LMs and short-term stability was performed by photon correlation spectroscopy (PCS) and a centrifugation test was also carried out. The results showed that NCTD-loaded LM (2 mg/ml) with over 80% NCTD loaded in the interfacial surface were stable for a period of 2 months, and were suitable for i.v. injection in terms of size and stability, whether be diluted or not. Such formulations produced less pain and irritation in animal studies.