Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles

Abstract

Objective: The essential aim of this article is to prepare solid lipid nanoparticles (SLNs) by emulsification and solvent displacement method and to determine the best process conditions to obtain submicron particles. Methods: The emulsification and solvent displacement method is a modification of the well-known emulsification–diffusion method, but without dilution of the system. The extraction of the partially water-miscible solvent from the emulsion globules is carried out under reduced pressure, which causes the diffusion of the solvent toward the external phase, with subsequent lipid aggregation in particles whose size will depend on the process conditions. The critical variables affecting the process, such as stirring rate, the proportion of phases in the emulsion, and the amount of stabilizer and lipid, were evaluated and optimized. Results: By this method, it was possible to obtain a high yield of solids in the dispersion for the lipids evaluated (Compritol^® ATO 888, Geleol^®, Gelucire^® 44/14, and stearic acid). SLNs of up to ∼20 mg/mL were obtained for all lipids evaluated. A marked reduction in size, between 500 and 2500 rpm, was seen, and a transition from micro- to nanometric size was observed. The smaller particle sizes obtained were 113 nm for Compritol^® ATO 888, 70 nm for Gelucire^® 44/14, 210 nm for Geleol^®, and 527 nm for stearic acid, using a rotor–stator homogenizer (Ultra-Turrax^®) at 16,000 rpm. The best phase ratio (organic/aqueous) was 1 : 2. Conclusions: The process proposed in this study is a new alternative to prepare SLNs with technological potential.

• Emulsification and solvent displacement
• emulsification–diffusion method
• lipids
• nanoparticles
• solid lipid nanoparticles