Effect of ultrasound and stabilizers on nucleation kinetics of curcumin during liquid antisolvent precipitation

Nucleation kinetics of liquid antisolvent precipitation of a poorly water soluble drug curcumin in presence of ultrasound and surfactants have been estimated. Ultrasound and stabilizers were found to have opposing effects on induction time (τ<inf>ind</inf>), metastable zone width (MSZW) and nucleation rates (J) of curcumin during antisolvent precipitation. The use of ultrasound (in presence or absence of stabilizers) was found to decrease τ<inf>ind</inf> and MSZW drastically while the values of nucleation rates were found to increase. In contrast to these observations, use of stabilizers (in presence or absence of ultrasound) were found to increase MSZW, increase τ<inf>ind</inf> and lower the nucleation rates (J) of curcumin. The solid-liquid interfacial energies (γ<inf>SL</inf>) for curcumin in aqueous ethanolic solutions (with and without stabilizers) have also been calculated using experimentally estimated induction time (τ<inf>ind</inf>) and supersaturation data. The values of solid-liquid interfacial energies were found to be in the range of 1.5-3.5 mJ/m². In comparison to these values, the values of γ<inf>SL</inf> predicted by Mersmann equation and equation proposed by Bennema and Sohnel were found to be significantly higher and were in the range of 10-30 mJ/m².