Formulation of an intravenous emulsion loaded with a clarithromycin–phospholipid complex and its pharmacokinetics in rats

The purpose of this paper is to prepare a new formulation of clarithromycin emulsion (ClaE) with the clarithromycin–phospholipid complex which was analyzed by DSC. High-pressure homogenization, Nicomp™ 380 Particle Sizing system, and HPLC were used to prepare and investigate ClaE, while UPLC/MS/MS for pharmacokinetic study. Clarithromycin and soybean lecithin were reacted in dehydrated alcohol at a ratio of 1:10 for 3 h at 65 °C to prepare the complex. The ClaE formulation consisted of, according to quality percentage, the complex (clarithromycin 0.25% in ClaE), LCT 4%, MCT 16%, soybean lecithin 1.0%, F68 0.2%, Tween80 0.2%, glycerol 2.5%, sodium oleate 0.1% and l-cysteine 0.02%. ClaE was sterilized in a 100 °C revolving water bath for 30 min. The drug content, particle size distribution and entrapment efficiency of ClaE before and after sterilization and over 6 months storage at 10 °C were almost unchanged, while ζ-potential increased from −20.32 mV to −23.71 mV. These results show that ClaE has enough physicochemical stability to undergo sterilization and storage. The pharmacokinetic study showed that both ClaE and ClaS fitted a three-compartment model, their pharmacokinetic curves were similar and the main parameters showed no significant difference except Vss. ClaE has a great potential for clinical applications and industrial-scale production.