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 thinfilm dispersed homogenization method. The...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 thinfilm 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.展开更多
Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to inv...Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate(GMS) as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets(ASA-ECT) was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.展开更多
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 thinfilm 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.
基金supported by the National Natural Science Foundation of China(No.81402858)the Liaoning Natural Science Foundation(No.2015020736)Shenyang Pharmaceutical University Long-term Training Fund(No.ZCJJ2014406)
文摘Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub-and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate(GMS) as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets(ASA-ECT) was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.
