Precipitation of curcumin using CO2-expanded acetone solution: experiments and mathematical modeling

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 edicinal 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 by increasing surface area and 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 minute's time. In this work it was found that the particle size, size distribution and polymorphic behavior of precipitated curcumin particles depend on initial pressure as well as on additives used. While particles precipitated mostly in monoclinic form, curcumin particles precipitated at 40 bar and with additives such as Tween 80 and Pluronic F 68 were found to precipitate as a mixture of orthorhombic and monoclinic forms. However for additive PEG, curcumin precipitated as mixture of rthorhombic and monoclinic forms when additive is in acetone solution. Further, a mathematical model was used to estimate supersaturation achieved, rate of nucleation, growth rate and particle sizes of curcumin precipitated by PPRGEL. Comparison of the experimental mean particle sizes with the predicted mean particle sizes suggests that at lower initial pressures, heterogeneous nucleation mechanism dominates to the particle formation process and at higher initial pressures, homogeneous nucleation mechanism seems to dominate the particle formation process.