College of Pharmacy and Health Sciences, St. John's University, Queens, New York 11439, United States.
Mol Pharm. 2023 May 1;20(5):2556-2567. doi: 10.1021/acs.molpharmaceut.2c01118. Epub 2023 Mar 28.
The self-nano/microemulsifying drug delivery system is one of the well-established techniques for enhancing the solubility of poorly water-soluble drug molecules. The ratio of oil:surfactant:cosolvent plays a key role in globule size on dispersion into water, but there is very limited information on how a drug molecule affects the size. The rationale of this project was to illustrate the correlation between the particle size of nanoemulsion droplets and molecular descriptors of a drug. In the study, a self-nanoemulsifying preconcentrate containing drug with medium chain triglycerides (oil), dimethylacetamide (DMA, cosolvent), and Kolliphor EL (surfactant) was prepared for 40 drug molecules with diverse physicochemical properties. The self-nanoemulsifying preconcentrate was dispersed in water, and dynamic light scattering particle size was analyzed. A majority of drugs showed a significant increase in globule size compared to blank formulation, while few drugs showed a stark reduction in globule size. It is interesting to understand the attributes of molecules driving the self-emulsification and the diameter of nanoglobules. A systematic correlation of resultant particle size with 1D, 2D, and 3D molecular descriptors (overall more than 700 descriptors) was carried out for the data set using the PaDEL tool kit. The data compilation, curation, and analysis were performed using the SIMCA14 software. In the process of molecular descriptors screening, thereafter curation, 50 descriptors were selected using the genetic algorithm screening. The PLS-DA statistical method was employed for conversion of data into binomial systems. Final group of 5 descriptors: SpMiSpMin2_Bhe, RNCS, TDB9i, JG17, and ETA_Shape showed the correlation with particle size and classifying the drug molecules facilitating increase or decrease in particle size.
自微纳米乳化药物传递系统是提高疏水性药物分子溶解度的成熟技术之一。油：表面活性剂：共溶剂的比例在分散到水中时对球粒大小起着关键作用，但关于药物分子如何影响大小的信息非常有限。本项目的原理是说明纳米乳滴的粒径与药物分子描述符之间的相关性。在研究中，制备了含有药物的自微乳前体浓缩物，该药物包含中链甘油三酯（油）、二甲基乙酰胺（DMA，共溶剂）和 Kolliphor EL（表面活性剂），用于 40 种具有不同物理化学性质的药物。自微乳前体浓缩物在水中分散，分析动态光散射粒径。与空白配方相比，大多数药物的液滴粒径显著增加，而少数药物的液滴粒径明显减小。了解驱动自乳化和纳米液滴直径的分子属性是很有趣的。使用 PaDEL 工具包对数据集进行了系统的相关研究，结果粒径与 1D、2D 和 3D 分子描述符（总共超过 700 个描述符）进行了相关性分析。数据编译、管理和分析使用 SIMCA14 软件进行。在分子描述符筛选过程中，经过管理，使用遗传算法筛选出 50 个描述符。PLS-DA 统计方法用于将数据转换为二项系统。最终的 5 个描述符组：SpMiSpMin2_Bhe、RNCS、TDB9i、JG17 和 ETA_Shape 显示出与粒径的相关性，并对药物分子进行分类，促进粒径的增加或减少。
