Schaefer M J, Singh J
Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.
Drug Dev Ind Pharm. 2001 Apr;27(4):345-50. doi: 10.1081/ddc-100103734.
The purpose of this article was to determine the shelf life of etoposide in poly(lactic-co-glycolic acid) (PLGA) microspheres prepared with and without additives (i.e., tricaprin and isopropyl myristic acid ester [IPM]). The microspheres were prepared by a single-emulsion solvent extraction technique with and without 25% w/w additive. The batches of microspheres were subjected to an accelerated stability study at two elevated temperatures (70 degrees C and 80 degrees C or 80 degrees C and 90 degrees C). Samples were taken at 7, 14, 21, 28, and 35 days for estimation of drug content by high-performance liquid chromatography (HPLC). The drug stability in the microspheres was determined by plotting the log percentage drug remaining versus time to obtain the degradation rate constant k of etoposide at the measured temperature. This degradation rate constant was then used in the Arrhenius equation to obtain the activation energy of etoposide, which was utilized to determine the shelf life of the microspheres at room temperature. The results showed that all three microsphere formulations had good long-term stability at room temperature (6.62-8.86 years at 25 degrees C). The plain microspheres were shown to possess a shelf life of 6.62 years, and the IPM and tricaprin were the most stable with shelf lives of 8.25 and 8.86 years, respectively.
本文的目的是确定依托泊苷在添加和未添加添加剂（即三辛酸甘油酯和肉豆蔻酸异丙酯[IPM]）的聚乳酸-乙醇酸共聚物（PLGA）微球中的保质期。微球采用单乳液溶剂萃取技术制备，添加和未添加25%w/w的添加剂。将微球批次在两个升高的温度（70℃和80℃或80℃和90℃）下进行加速稳定性研究。在第7、14、21、28和35天取样，通过高效液相色谱法（HPLC）测定药物含量。通过绘制剩余药物对数百分比与时间的关系图来确定微球中药物的稳定性，以获得在测量温度下依托泊苷的降解速率常数k。然后将该降解速率常数用于Arrhenius方程，以获得依托泊苷的活化能，该活化能用于确定微球在室温下的保质期。结果表明，所有三种微球制剂在室温下均具有良好的长期稳定性（25℃下为6.62 - 8.86年）。未添加添加剂的微球保质期为6.62年，IPM和三辛酸甘油酯最稳定，保质期分别为8.25年和8.86年。
