Quality by Design-Based Crystallization of Curcumin Using Liquid Antisolvent Precipitation: Micromeritic, Biopharmaceutical, and Stability Aspects.

The aim of present study was to introduce the role of quality by design to produce curcumin crystals with enhanced dissolution rate and bioavailability. The liquid antisolvent method was used to produce crystals. The crystal growth was controlled using the Box-Behnken design. The variables used in the crystallization process included the ratio of pyrocatechol to polyethylene glycol (PEG) 1500, solvent addition rate, stirring time, and stirring speed. Combination of these variables was found to yield curcumin crystals of 2.45 ± 0.56 μm size and 0.321 polydispersity index that exhibited enhanced solubility, dissolution rate, product yield, and compressibility. The optimized curcumin crystals were characterized by Fourier-transform infrared spectrophotometer (FT-IR), nuclear magnetic resonance, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. The dissolution rate and oral bioavailability of optimized curcumin crystals were found to be 2.66- and 7.08-folds higher than its unprocessed form. The optimized crystals were found stable for 6 months under accelerated temperature of 40°C and 75% relative humidity as there was no significant difference observed in the crystal size and dissolution profile.