Kannan Vinayagam, Balabathula Pavan, Divi Murali K, Thoma Laura A, Wood George C
a Department of Pharmaceutical Sciences , The University of Tennessee Health Science Center , Memphis , TN , USA and.
b Plough Center for Sterile Drug Delivery, The University of Tennessee Health Science Center , Memphis , TN , USA.
J Liposome Res. 2015;25(4):308-15. doi: 10.3109/08982104.2014.995671. Epub 2014 Dec 26.
The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.
评估了制剂和工艺参数对载紫杉醇长循环脂质体载药量和物理稳定性的影响。脂质体采用水化挤压法制备。研究了总脂质含量、胆固醇含量、饱和-不饱和脂质比例、药物-脂质比例等制剂参数以及挤压压力和挤压循环次数等工艺参数，并评估了它们对载药量和物理稳定性的影响。随着总磷脂含量的增加，载药量呈相应增加。双层膜中的胆固醇含量和饱和脂质含量对载药量有负面影响。对不同药物-脂质比例制备的脂质体进行的短期稳定性评估表明，1:60是实现1-1.3mg/mL载药量且无物理不稳定风险的最佳药物-脂质比例。随着挤压压力和挤压循环次数的增加，囊泡尺寸减小，但随着工艺压力或循环次数的变化，载药量未观察到显著趋势。制剂和工艺参数的优化导致了载紫杉醇长循环脂质体的物理稳定制剂，该制剂在储存期间保持大小、电荷和完整性。
