Precipitation of advanced nanomedicines (curcumin) using supercritical processing; experimental study, design and optimizing operating conditions

Abstract

Curcumin is a known herbal medicine with numerous therapeutic effects and low bioavailability. Reducing the particle size of this medicine is a confirmed solution to increase its dissolution rate and bioavailability. To do so, Curcumin nanoparticles were produced in the present work by the supercritical gas anti-solvent (GAS) method. First, the minimum GAS operating pressure (Pmin) required to precipitate fine Curcumin particles from two solvents DMSO and ethanol was estimated using Peng-Robinson equation of state (PR-EoS). Then, Curcumin nanoparticles were precipitated from these two solvents under different operating conditions, specified by the Box–Behnken design method. Given the desired operating variables including pressure (120, 180, and 240 bar), temperature (308, 328, and 348 K), initial concentration (5, 35, and 65 mg/ml), flow rate of the supercritical carbon dioxide (scCO2) (10, 50, and 90 ml/min), and stirring rate (500, 1500, and 2500 rpm), their influence on the particle size of Curcumin was investigated, and optimum conditions were determined. At 240 bar and 328 K, nano Curcumin particles with the size of 230 nm and 81 nm were precipitated from DMSO and ethanol solutions with the initial concentration of 5 mg/ml and stirring rate of 1500 rpm, respectively. Results show that scCO2 flow rate is not a significant parameter.The remarkable reduction in the particle size of Curcumin from 28 ± 10 μm of the original sample to nano-scale confirms GAS efficiency. Also, the dissolution rate of the nanoparticles, produced in the optimal condition is much higher than the original sample, which can be due to their nano-metric size and lower degree of crystallinity.