Vemuri S, Rhodes C T
Department of Pharmaceutics, College of Pharmacy, University of Rhode Island, Kingston 02881-0809.
J Pharm Pharmacol. 1994 Oct;46(10):778-83. doi: 10.1111/j.2042-7158.1994.tb03729.x.
A pH gradient across liposome bilayers was established in order to load a model drug (orciprenaline sulphate) into liposome vesicles. This method of liposome loading resulted in yields as high as 80-85% encapsulation. An eight-step process was designed to scale-up the process and was evaluated. In this process a diafiltration technique was successfully used to remove the excess orciprenaline sulphate present in the external medium. Finally, drug-loaded liposomes were lyophilized using lactose as an internal and external liposomal cryoprotectant. Five-month stability data for the liposomes is reported. An HPLC technique was used to determine the drug concentration and a laser light-scattering technique was employed to determine the liposome vesicle size and polydispersity factor. Liposomes prepared by the pH-gradient method showed high encapsulation efficiency. Upon storage at 2-8 degrees C the vesicle size increased and encapsulation efficiency decreased with time. These phenomena are attributed to gradual fusion of liposomes and loss of drug to the extra-liposomal media.
为了将模型药物（硫酸奥西那林）载入脂质体囊泡，在脂质体双层膜上建立了pH梯度。这种脂质体载入方法的包封率高达80 - 85%。设计了一个八步流程来扩大该工艺规模并进行了评估。在此过程中，成功使用了渗滤技术来去除外部介质中存在的过量硫酸奥西那林。最后，使用乳糖作为脂质体内外的冷冻保护剂，对载药脂质体进行冻干。报告了脂质体五个月的稳定性数据。使用高效液相色谱技术测定药物浓度，并采用激光散射技术测定脂质体囊泡大小和多分散性因子。通过pH梯度法制备的脂质体显示出高包封效率。在2 - 8℃储存时，囊泡大小随时间增加，包封效率随时间降低。这些现象归因于脂质体的逐渐融合以及药物向脂质体外介质的损失。
