Preparation of stabilized lidocaine particles by a combination of supercritical CO₂ technique and particle surface control

摘要

Lidocaine particles were prepared by the rapid expansion of the supercritical fluids into aqueous solution (RESAS). About 150–300 nm lidocaine particles could be temporarily observed when collected in water at concentration of 10 mg/cc, but the particles developed into 50 μm needle crystals just 30 min later. To prevent the fast aggregation of the particles as well as further crystal growth, modifications on particle surfaces by adding surfactants and introduction of electrostatic repulsion between particles were conducted. When a surfactant (sucrose stearic acid ester S-1570) was added to the collecting aqueous solution, the particle growth was alleviated and no large needle crystals were formed. However, the long-term stability needs to be improved because the lidocaine particles tend to grow from submicron to a few microns in a few days even stored in the 1% S-1570 solution. Electrostatic repulsion between particles is found effective to stabilize the submicron particles during the storage. When the pH value of the aqueous solution with 1% S-1570 was adjusted to 8.5 by adding KOH, the lidocaine particles suspending in this solution showed good stability that the particle size was able to be controlled in submicron level in 3 months.