Nimodipine-loaded mixed micelles: formulation, compatibility, pharmacokinetics, and vascular irritability study

Abstract

Xu Song,1* Yu Jiang,2* Chunjuan Ren,1 Xun Sun,1 Qiang Zhang,3 Tao Gong,1 Zhirong Zhang1 1Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 2Center for Drug Evaluation, State Food and Drug Administration, 3State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Peking, People's Republic of China*These authors contributed equally to this workBackground: The clinical application of nimodipine (NIM) is limited by several unfavorable properties, which are induced by its low aqueous solubility. In the present study, nimodipine-loaded egg phosphatidylcholine-sodium glycocholate mixed micelles (NIM-EPC-SGC-MMs) were prepared to improve the water solubility of NIM, thus allowing it to be more applicable for clinical use.Methods: NIM-EPC-SGC-MMs were prepared using the coprecipitation method and the factors influencing formulation quality were optimized. After formulation, water solubility, solubilizing efficiency, drug loading, particle size, physical compatibility, pharmacokinetics, and vascular irritability were determined.Results: The mean size of the NIM-EPC-SGC-MMs was 6.099 ± 0.048 nm under optimized conditions. The water solubility of NIM in EPC-SGC-MMs was enhanced 250-fold compared with free NIM. The physical compatibility, pharmacokinetic, and vascular irritability studies showed that, in comparison to the commercially available NIM injections, NIM-EPC-SGC-MMs presented better physical compatibility, the same pharmacokinetic profile, and less risk of local vascular irritation and phlebitis.Conclusion: EPC-SGC-MMs represent a promising new formulation suitable for the intravenous delivery of NIM.Keywords: drug loading, nimodipine injection, physical compatibility, solubilizing efficiency