Subcutaneously injected ivermectin-loaded mixed micelles: formulation, pharmacokinetics and local irritation study

Abstract

Clinical application of ivermectin (IVM) is limited by several unfavorable properties, induced by its insolubility in water. Slight differences in formulation may change the plasma pharmacokinetics and efficacy. In this study, an IVM-loaded Soy phosphatidylcholine-sodium deoxycholate mixed micelles (IVM-SPC-SDC-MMs) were developed to improve its aqueous solubility, aiming to make it more applicable for clinical use. First, IVM-SPC-SDC-MMs were prepared using the co-precipitation method. After formulation optimization, the particle size was 9.46 ± 0.16 nm according to dynamic light scattering. The water solubility of IVM in SPC-SDC-MMs (4.79 ± 0.02 mg/mL) was improved by 1200-fold, comparing with free IVM (0.004 mg/mL). After subcutaneous administration, the pharmacokinetic study showed that IVM-SPC-SDC-MMs and commercially available IVM injection were bioequivalent. Also, the local irritation study confirmed that IVM-SPC-SDC-MMs reduced side reactions of the commercially available IVM injection. These results indicated that IVM-SPC-SDC-MMs represented a promising new drug formulation suitable for subcutaneous delivery of IVM.

Keywords:

• Ivermectin
• local irritation
• mixed micelles
• pharmacokinetic
• soy phosphatidylcholine-sodium–deoxycholate

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

This research was supported by the National Basic Research Program of China (973 program, no. 2013CB932504) and the National S & T Major Project of China (grant no. 2012ZX09304004001).