Lu Yan, Wang YanJiao, Tang Xing
Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, China.
Int J Pharm. 2008 Jan 4;346(1-2):47-56. doi: 10.1016/j.ijpharm.2007.06.003. Epub 2007 Jun 14.
The purpose of this study is to develop a less painful intravenous clarithromycin emulsion (ClaE) and investigate its thermal sterile stability. The formulation of ClaE is composed of clarithromycin 0.25% (w/v), vitamin E 5% (w/v), medium chain triglyceride (MCT) 10% (w/v), egg lecithin 1.0% (w/v), Cremophor EL-40 (EL-40) 2% (w/v), Pluronic F-68 (F-68) 0.2% (w/v), Tween80 0.2% (w/v), glycerol 2.5% (w/v) and L-cysteine 0.05% (w/v) in water. High-pressure homogenization, photon correlation spectroscopy (PCS) and electrophoretic light scattering (ELS) technology, light microscopy and high-performance liquid chromatography (HPLC) methods were used in the preparation and evaluation of ClaE. Investigation of thermal sterile stability included the effects of different thermal sterile methods, thermal sterile time, drug concentrations and pH values. Sterilization in a 100 degrees C rotating water bath for 30 min was finally adopted as the sterilization method. The drug remaining was 98.6% and 96.5%, respectively, before and after thermal sterilization. Moreover, the pH value, particle size distribution (PSD), zeta-potential and entrapment efficiency (EE) of ClaE after sterilization were 7.95, 213.6 nm, -22.29 mV and 96.35%, respectively. This showed that ClaE had sufficient physicochemical stability to resist the sterilization process. Tests using animal models demonstrated that there was a marked pain reduction following the injection of ClaE compared with clarithromycin solution. Overall, ClaE described in this paper may be very suitable for industrial-scale production and clinical application.
本研究的目的是开发一种疼痛较轻的静脉注射用克拉霉素乳剂（ClaE），并研究其热无菌稳定性。ClaE的配方由0.25%（w/v）的克拉霉素、5%（w/v）的维生素E、10%（w/v）的中链甘油三酯（MCT）、1.0%（w/v）的蛋黄卵磷脂、2%（w/v）的聚氧乙烯蓖麻油EL-40（EL-40）、0.2%（w/v）的普朗尼克F-68（F-68）、0.2%（w/v）的吐温80、2.5%（w/v）的甘油和0.05%（w/v）的L-半胱氨酸在水中组成。在ClaE的制备和评价中使用了高压均质化、光子相关光谱（PCS）和电泳光散射（ELS）技术、光学显微镜和高效液相色谱（HPLC）方法。热无菌稳定性研究包括不同热无菌方法、热无菌时间、药物浓度和pH值的影响。最终采用在100℃旋转水浴中灭菌30分钟作为灭菌方法。热灭菌前后药物残留量分别为98.6%和96.5%。此外，灭菌后ClaE的pH值、粒度分布（PSD）、ζ电位和包封率（EE）分别为7.95、213.6nm、-22.29mV和96.35%。这表明ClaE具有足够的物理化学稳定性以抵抗灭菌过程。使用动物模型的试验表明，与克拉霉素溶液相比，注射ClaE后疼痛明显减轻。总体而言，本文所述的ClaE可能非常适合工业规模生产和临床应用。
