Stability mechanisms for microwave-produced solid lipid nanoparticles

Abstract

Tween® 20 stabilised stearic acid solid lipid nanoparticles (SLNs) were prepared using a one-pot microwave-assisted microemulsion technique. Two model water-insoluble drugs, the carboxylic acid-based indomethacin, and the imidazole-based miconazole nitrate, were then used to load the SLNs, and their subsequent physical properties (particle size and zeta potential) were measured and used to predict dispersion stability.Drug-free SLNs had a particle size of 239 nm and a zeta potential of − 29 mV. Indomethacin-loaded SLNs had a particle size of 266 nm and zeta potential of − 30 mV. Miconazole-loaded SLNs had a particle size of 266 nm and zeta potential of + 15 mV. These values were found to be relatively stable (under mildly acidic conditions) and recommend the suitability of the SLNs as a drug carrier.In all cases, the particle size and zeta potential were shown to be pH-dependent. For particle size, a minimum value was obtained at approximately pH 5, which corresponds to the pKa of the lipid used (stearic acid) indicating stearic acid adsorption onto the surface is likely to be at least partly responsible for dispersion stability. We conclude that dispersion stability arises from a combination of electrostatic stability (from adsorbed stearic acid) and limited steric stability from non-ionic (Tween® 20) surface-associated micelles.Dispersions were found to be unstable under alkaline conditions despite the increasingly negative zeta potential of all dispersions. This was observed as an increasingly larger particle size at pH > 7 combined with the observation that particle sizes at pH > 7 were also unstable and continued to increase with time. Visual observations showed dispersions physically broke within a few days at pH values > 7.The encapsulation efficiency (EE) and loading capacity (LC) of drug-loaded SLNs were shown to be close to their theoretical maximum (100%) at low pH, but decreased to < 20%, in the case of indomethacin-loaded SLNs, at a pH >> 7. Interestingly, the EE and LC of miconazole-loaded SLNs when first formed were relatively unaffected by pH. pH control, therefore, is very important to particle stability, and the pH should be kept neutral to mildly acidic.