Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, CT 06269, United States.
Int J Pharm. 2012 Feb 28;423(2):410-8. doi: 10.1016/j.ijpharm.2011.12.019. Epub 2011 Dec 21.
A mathematical model has been developed to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes, and will be useful in formulation development to rapidly achieve optimized formulations. This model can also be used to compare drug encapsulation efficiencies of liposomes prepared via different methods, and will assist in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during liposome manufacturing for hydrophilic molecules. Liposome particle size as well as size distribution, lipid concentration, lipid molecular surface area, and bilayer thickness were used in constructing the model. Most notably, a Log-Normal probability function was utilized to account for sample particle size distribution. This is important to avoid significant estimation error. The model-generated predictions were validated using experimental results as well as literature data, and excellent correlations were obtained in both cases. A Langmuir balance study provided insight regarding the effect of media on the liposome drug encapsulation process. The results revealed an inverse correlation between media ionic strength and lipid average molecular area, which helps to explain the phenomenon of inverse correlation between media ionic strength and drug encapsulation efficiency. Finally, a web application has been written to facilitate use of the model allowing calculations to be easily performed. This model will be useful in formulation development to rapidly achieve optimized formulation.
已经开发出一种数学模型来预测亲水性药物在单层脂质体中的包封效率，这将有助于制剂开发，从而快速实现优化的配方。该模型还可用于比较通过不同方法制备的脂质体的药物包封效率，并有助于开发合适的过程分析技术，以实现对亲水分子脂质体制造过程中药物包封的实时监测和控制。该模型使用了脂质体粒径以及粒径分布、脂质浓度、脂质分子表面积和双层厚度来构建。值得注意的是，利用对数正态概率函数来解释样品粒径分布。这一点很重要，可以避免估计误差过大。使用实验结果和文献数据对模型生成的预测进行了验证，两种情况下都得到了很好的相关性。Langmuir 平衡研究提供了关于介质对脂质体药物包封过程影响的见解。结果表明，介质离子强度与脂质平均分子面积之间呈反比关系，这有助于解释介质离子强度与药物包封效率之间的反比关系现象。最后，编写了一个网络应用程序来方便使用该模型，从而可以轻松地进行计算。该模型将有助于制剂开发，从而快速实现优化的配方。
