Lenor Zeeh Pharmaceutical Experiment Station, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, Wisconsin 53705, USA.
AAPS PharmSciTech. 2012 Dec;13(4):1103-9. doi: 10.1208/s12249-012-9830-3. Epub 2012 Aug 21.
The purpose of this research was to investigate the relationship of drug solubility in a complex lipid mixture to that of the individual ingredients with the goal of substantiating a quantitative equation that can be applied in formulation development of lipid dosage forms. To this end, the solubility of four drugs, which span a large range of physicochemical properties, was evaluated in 18 lipid ingredients that cover the major lipid classes. To assess the solubility relation in complex lipid mixtures in an unbiased manner, the experiments were created as an experimental design with the ability to detect cubic curvature in the solubility-lipid composition space. The results demonstrated that for all drugs, irrespective of their significantly distinct physicochemical properties, solubility in lipid mixtures can be readily estimated as a simple weighted average of the drug solubility in the individual ingredients. This result is of great value to formulators who can minimize a large number of solubility experiments once a basis set of solubility is determined in individual lipids.
本研究旨在探讨药物在复杂脂质混合物中的溶解度与各成分溶解度之间的关系，以期建立一个可应用于脂质剂型制剂开发的定量方程。为此，评估了跨越广泛物理化学性质范围的四种药物在涵盖主要脂质类别的 18 种脂质成分中的溶解度。为了以无偏方式评估复杂脂质混合物中的溶解度关系，实验设计为具有在溶解度-脂质成分空间中检测立方曲率的能力。结果表明，对于所有药物，无论其物理化学性质有多么明显的不同，均可将其在脂质混合物中的溶解度作为药物在各成分中的溶解度的简单加权平均值来轻松估算。这一结果对于制剂开发者具有重要意义，因为一旦确定了各脂质中的溶解度基础数据集，他们就可以大大减少大量溶解度实验。
