Precipitation of curcumin by pressure reduction of CO2-expanded acetone

Abstract

In this work, a technique of precipitation by pressure reduction of gas-expanded liquids (PPRGEL) has been utilized to precipitate ultra-fine particles of curcumin. Curcumin is a natural and pharmaceutically viable compound found in Indian spice, turmeric and possesses several medicinal properties. However, it suffers from low bioavailability due to its poor solubility in aqueous medium. Precipitation of ultrafine particles of such compounds improves their bioavailability due to increase in surface area and hence the dissolution rates. The PPRGEL process precipitates ultra-fine particles by generating large, rapid and uniform supersaturation in the solution produced by a sudden and large reduction (40–70K) in the solution temperature in a very short time (as low as 1min). In this work it was found that the particle size, size distribution and polymorphic behaviour of precipitated curcumin particles depends on initial CO2 pressure as well as on the additives used. Curcumin particles mostly precipitated in monoclinic form. However, curcumin particles precipitated at 40bar and with additives such as Tween 80 and PF68 were found to precipitate as a mixture of orthorhombic and monoclinic forms. Dissolution studies show that the precipitated curcumin particles dissolve faster than raw curcumin. Further, a mathematical model was used to estimate supersaturation, nucleation rates, growth rates and average sizes of particles precipitated by PPRGEL. Comparison of experimental particle sizes with the predicted particle sizes suggests that at lower initial pressures, heterogeneous nucleation mechanism dominates the particle formation process and at higher initial pressures, homogeneous nucleation mechanism seems to dominate the particle formation process.