Solvent injection-lyophilization of tert-butyl alcohol/water cosolvent systems for the preparation of drug-loaded solid lipid nanoparticles.

A simple procedure involving solvent injection-lyophilization (SIL) was used to prepare solid lipid nanoparticles (SLNs). A tert-butyl alcohol (t-BA) solution containing lipids was injected into a stirred aqueous solution containing lyoprotectants to form SLNs dispersed in a t-BA/water cosolvent system. The t-BA/water cosolvent SLN dispersion was subsequently lyophilized to obtain a dry product which, upon rehydration, formed an aqueous dispersion of spherical SLNs with a size under 200 nm. A lipophilic drug, cinnarizine, was dissolved in t-BA at a drug-to-lipid mass ratio of 1:20 and almost 100% of the drug was entrapped in the formed SLNs following the SIL process. Likewise, hydrophilic 5-fluorouracil, after being solubilized in t-BA through forming anhydrous reverse micelles, could be entrapped in SLNs with an encapsulation efficiency up to 15.6%. Differential scanning calorimetry and small angle X-ray scattering analysis proved that the lipids in the formed SLNs were in a stable beta-form, and there was no recrystallization expulsion of drugs during storage. In contrast to the conventional solvent injection method, the SIL procedure was not time-consuming and no relatively high-temperature evaporation was needed to remove organic solvents. Moreover, the efficiency of the lyophilization was markedly enhanced due to use of the t-BA/water cosolvent system. Thus, the SIL procedure was found to be an efficient method for preparing stable drug-loaded SLNs. Copyright 2010 Elsevier B.V. All rights reserved.