Statistical analysis of solid lipid nanoparticles produced by high-pressure homogenization: a practical prediction approach

Abstract

Lipid nanoparticles (LNPs) are a promising carrier for all administration routes due to their safety, small size, and high loading of lipophilic compounds. Among the LNP production techniques, the easy scale-up, lack of organic solvents, and short production times of the high-pressure homogenization technique (HPH) make this method stand out. In this study, a statistical analysis was applied to the production of LNP by HPH. Spherical LNPs with mean size ranging from 65 nm to 11.623 μm, negative zeta potential under –30 mV, and smooth surface were produced. Manageable equations based on commonly used parameters in the pharmaceutical field were obtained. The lipid to emulsifier ratio (R L/S) was proved to statistically explain the influence of oil phase and surfactant concentration on final nanoparticles size. Besides, the homogenization pressure was found to ultimately determine LNP size for a given R L/S, while the number of passes applied mainly determined polydispersion. α-Tocopherol was used as a model drug to illustrate release properties of LNP as a function of particle size, which was optimized by the regression models. This study is intended as a first step to optimize production conditions prior to LNP production at both laboratory and industrial scale from an eminently practical approach, based on parameters extensively used in formulation.