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

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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.

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Acknowledgments

M. D. L. thanks University of Seville for a Grant from IV Research Plan of University of Seville. L. M. B. is especially grateful to Junta de Andalucía (Spain) for financial support (Project No. P09-CTS5029). Microscopy Services (Centro de Investigación, Tecnología e Innovación de la Universidad de Sevilla, CITIUS) technical support is also grateful. Authors also thank Dr. Álvarez-Fuentes for technical support.

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Authors and Affiliations

  1. Dpto. Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/Prof. García González n°2, 41012, Seville, España

    Matilde Durán-Lobato, Mercedes Fernández-Arévalo & Lucía Martín-Banderas

  2. Dpto. Estadística e Investigación Operativa, Facultad de Matemáticas, Universidad de Sevilla, C/Tarfia s/n, 41012, Seville, España

    Alicia Enguix-González

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  1. Matilde Durán-Lobato
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  3. Mercedes Fernández-Arévalo
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Correspondence to Matilde Durán-Lobato.

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Durán-Lobato, M., Enguix-González, A., Fernández-Arévalo, M. et al. Statistical analysis of solid lipid nanoparticles produced by high-pressure homogenization: a practical prediction approach. J Nanopart Res 15, 1443 (2013). https://doi.org/10.1007/s11051-013-1443-6

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  • DOI: https://doi.org/10.1007/s11051-013-1443-6

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