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 degrees 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 degrees 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 degrees C were almost unchanged, while zeta-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.
Lu
Yan
Y
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Zhang
Yu
Y
Yang
Ziyi
Z
Tang
Xing
X
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D054709:Lecithins / Q000737:chemistry*; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry; D013242:Sterilization; D053719:Tandem Mass Spectrometry
D000900:Anti-Bacterial Agents; D004655:Emulsions; D005079:Excipients; D054709:Lecithins; D017291:Clarithromycin