Influence of process and formulation parameters on the preparation of solid lipid nanoparticles by dual centrifugation

A promising strategy to formulate poorly water-soluble active pharmaceutical ingredients (APIs) is the application of these substances in solid lipid nanoparticles. These drug carrier systems are commonly prepared by high-pressure homogenization above the melting temperature of the utilized lipid.

While being very useful for large-scale production this method is quite resource-consuming and does not allow simultaneous processing of multiple samples, e.g. for screening purposes. For this reason, an alternative manufacturing process, dual centrifugation, is introduced to prepare solid lipid nanoparticles. The ingredients of the dispersions were directly weighed into 2 mL vessels at room temperature without the need to prepare a pre-mix emulsion. Due to an additional rotation of the samples in the heated centrifuge as well as the addition of grinding media an intensive stressing of the samples was achieved.

The emulsification process was finished within 10 min with sample temperatures of up to 90 °C being obtained. Dependent on the process set-up like grinding media size, filling ratio or process temperature and the composition of the lipid formulation, the achieved particles sizes were below 200 nm and had a narrow, monomodal size distribution.

Download the full article as a PDF here or read it here

Materials: The triglycerides trimyristin (Dynasan® 114, Tm = 56 °C), tripalmitin (Dynasan® 116, Tm = 66 °C) and tristearin (Dynasan® 118, Tm = 73 °C) from Hüls AG/Cremer Oleo (Witten, Germany) were kind gifts from the manufacturer. For the stabilization of the dispersions, poloxamer 188 (P188, Kolliphor® P188, BASF, Ludwigshafen, Germany; kind gift from manufacturer) was used. Sodium azide (Roth, Karlsruhe, Germany) was used as preservative. For all formulations bidistilled water was used.

The formulations were prepared in 2 mL DC-Twist-Top-vials from Andreas Hettich GmbH & Co KG (Tuttlingen, Germany; kind gift from the manufacturer). Yttrium stabilized zirconium dioxide beads were used in four different sizes (dGM = 0.1–0.2 mm, 0.3–0.4 mm, 0.5–0.7 mm and 0.8–1.0 mm) from Sigmund Lindner GmbH (Warmensteinach, Germany). The beads had a spherical shape and a material density of ρGM = 6.05 kg dm−3.

Article information: Denise Steiner, Heike Bunjes. Influence of process and formulation parameters on the preparation of solid lipid nanoparticles by dual centrifugation, International Journal of Pharmaceutics: X, Volume 3, 2021.

You might also like