Multivariate design for the evaluation of lipid and surfactant composition effect for optimisation of lipid nanoparticles

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Susana Martins (Author) Other; Ingunn Tho (Author) Other; Eliana Souto (Author) Other; Domingos Ferreira (Author) FFUP; Martin Brandl (Author) Other

Journal

Title: European Journal of Pharmaceutical Sciences

Vol. 45

Pages: 613-623

ISSN: 0928-0987

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 38 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-B32

DOI: 10.1016/j.ejps.2011.12.015

Abstract (EN): Physicochemical properties of lipid nanoparticles (LN), such as size, size distribution and surface charge, have a major influence both, on in vitro stability and delivery of the incorporated drug in vivo. With the purpose of understanding how these properties are influenced by variations of LN composition (e.g. lipid and surfactant type and concentration) 2(2) factorial designs with centre point were applied for several types of lipids and surfactants in the present study. Tested factors and levels were the type and concentration of lipid (cetyl palmitate, Dynasan 114 and Witepsol E85) at the concentrations of 5%, 10% and 15%, in combination with type and concentration of surfactant (polysorbate 20, 40, 60 and 80 and poloxamer 188 and 407) at concentrations of 0.8%, 1.2% and 2.0%. Responses measured within the design space were the mean size and polydispersity index (photon correlation spectroscopy), content of microparticles (optical single particle sizing), macroscopic appearance, pH and zeta potential on the day of production, 1 and 2 years after production. Multivariate evaluation and modelling were performed starting with a principal component analysis (PCA) and followed by partial least square regression analysis (PLS) to assess both qualitative and quantitative influence of the investigated factors in the LN. Our study showed that both, lipid and surfactant concentration and the type of surfactant are crucial parameters for the particle size of the LN prepared by high pressure homogenisation (HPH). For LN stability during 2 years both, lipid and surfactant types and concentrations were identified as the most relevant parameters. Among the surfactants most suitable for producing LN with small sizes were the polysorbates and the lipid yielding best storage stability was cetyl palmitate. Furthermore, the models allowed the prediction of the mean size of LN that could be achieved with a certain lipid/surfactant combination and concentration. The obtained results are considered useful for future design of stable LN formulations without the need of extensive empirical testing of formulation parameters within the given HPH technology.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11