An intravenous clarithromycin lipid emulsion with a high drug loading, H-bonding and a hydrogen-bonded ion pair complex exhibiting excellent antibacterial activity

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• 作者：Haoyu Gong ; Sicong Geng ; Qi Zheng ; Puxiu Wang ; Lifeng Luo ; Xiuzhi Wang ; Yan Zhang ; Yu Zhang ; Haibing He ; Xing Tang ; ^{tanglab@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Clarithromycin ; Cholesteryl hemisuccinate ; H-bonding and hydrogen-bonded ion pair complex ; Antibacterial activity ; Thin-film dispersed homogenization
• 刊名：Asian Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：11
• 期：5
• 页码：618-630
• 全文大小：2033 K

文摘

The aim of this study was to develop an intravenous clarithromycin lipid emulsion (CLE) with good stability and excellent antibacterial activity. The CLE was prepared by the thin-film dispersed homogenization method. The interaction between clarithromycin (CLA) and cholesteryl hemisuccinate (CHEMS) was confirmed by DSC, FT-IR and ¹H NMR analysis. The interfacial drug loading, thermal sterilization, freeze–thaw stability, and in vitro and in vivo antibacterial activity were investigated systematically. DSC, FT-IR and ¹H NMR spectra showed that CHEMS (CLA: CHEMS, M ratio 1:2) could interact with CLA through H-bonding and a hydrogen-bonded ion pair. The CHEMS was found necessary to maintain the stability of CLE. Ultracentrifugation showed that almost 88% CLA could be loaded into the interfacial layer. The optimized CLE formulation could withstand autoclaving at 121 °C for 10 min and remain stable after three freeze–thaw cycles. The in vitro susceptibility test revealed that the CLA–CHEMS ion-pair and CLE have similar activity to the parent drug against many different bacterial strains. The in vivo antibacterial activity showed that the ED₅₀ of intravenous CLE was markedly lower than that of CLA solution administrated orally. CLE exhibited pronounced antibacterial activity and might be a candidate for a new nanocarrier for CLA with potential advantages over the current commercial formulation.