Zhang Dianrui, Tan Tianwei, Gao Lei, Zhao Wenfa, Wang Peng
College of Life Science and Technology, Beijing University of Chemical Technology, Bei Sanhuan Donglu, Beijing, PR China.
Drug Dev Ind Pharm. 2007 May;33(5):569-75. doi: 10.1080/03639040600975147.
The azalide azithromycin was proved to be clinically effective against Gram-positive and Gram-negative bacteria. But the low bioavailability caused by its poor solubility and gastrointestinal response limited its application in clinic. With the purpose of increasing its saturation solubility and dissolution velocity, azithromycin was produced as nanosuspensions by high pressure homogenization. Nanosuspensions could increase the drug-loading and reduce the administration dosage, thus the gastrointestinal response could be minimized. In order to enhance the stability of the nanosuspensions, we got the freeze-dried powder by lyophilization. After dispersed in distilled water, the nanoparticles had a bulk population of about 400 nm and a spherical figure (watched by transmission electron microscopy). The analysis of differential scanning calorimetry and powder X-ray diffraction demonstrated that the crystal state of azithromycin had changed. In vitro release studies showed that the dissolution rate of nanosuspension, compared with micronized powder, had been obviously increased.
氮杂内酯类阿奇霉素已被证明对革兰氏阳性菌和革兰氏阴性菌具有临床疗效。但其溶解度差导致生物利用度低以及胃肠道反应限制了它在临床上的应用。为了提高其饱和溶解度和溶解速度，通过高压均质法将阿奇霉素制成纳米混悬液。纳米混悬液可以增加载药量并减少给药剂量，从而将胃肠道反应降至最低。为了提高纳米混悬液的稳定性，我们通过冻干得到了冻干粉。分散于蒸馏水中后，纳米颗粒的大量群体约为400nm，呈球形（通过透射电子显微镜观察）。差示扫描量热法和粉末X射线衍射分析表明阿奇霉素的晶态发生了变化。体外释放研究表明，与微粉化粉末相比，纳米混悬液的溶解速率明显提高。
