注射用克拉霉素乳剂的制备及其体内外评价

Preparation and evaluation of clarithromycin emulsion for injection

目的制备克拉霉素乳剂并考察其刺激性和体内药物动力学行为。方法通过高压均质方法制备克拉霉素乳剂,并对其性质进行研究。以克拉霉素溶液剂为对照,观察了乳剂的刺激性和在大鼠体内的药物动力学行为。结果高压均质法制备克拉霉素乳剂,平均粒径为156 nm,zeta电位为-31.8 mV。于4℃留样观察6个月内样品稳定。与克拉霉素溶液剂相比,乳剂可以明显降低刺激性。两种制剂在大鼠体内的药物动力学曲线相似,符合双隔室模型。克拉霉素乳剂和溶液剂AUC0-t分别为(66.76±16.34)和(59.00±11.20)μg.h.mL-1。结论高压均质法可以制备出性质稳定的载药乳剂,克拉霉素乳剂可以明显降低静脉注射时引起的刺激性。

Aim To prepare clarithromycin emulsion and investigate its pharmacokinetics in rats. And to do irritation test of the emulsion. Methods High pressure homogenization method was used to prepare clarithromycin emulsion, and the Nicomp380 machine was used to test the mean particle size and zeta-potential of clarithromycin emulsion. Irritation of emulsion was also evaluated compared with the positive control of clarithromycin solution using rat paw lick test and rabbit ear vein irritation test. Microbiological assay method was used for determining the drug concentration in plasma. Pharmacokinetics of two dosage forms in rats was also studied. Results The mean particle size and zeta potential of clarithromycin emulsion were 156 nm and -31.8 mV, respectively. The emulsion was stable during the storage time at 4 ℃ for 6 month. The pain caused by emulsion reduced significantly compared with that of clarithromycin solution based on the results of rat paw lick test and rabbit ear vein test. The drug concentration-time curves of clarithromycin emulsion and clarithromycin solution were similar and could be described by two compartment model. AUC0-1 of clarithromycin emulsion and clarithromycin solution were （66.76± 16.34） and （59.00 ± 11.20） /μg · h · mL^-1, respectively. Conclusion Stable emulsion could be prepared using high pressure homogenization method, and irritation caused by iv injection could be reduced significantly by using clarithromycin emulsion.