Particle formation pathways and polymorphism of curcumin induced by ultrasound and additives during liquid antisolvent precipitation

Precipitation of curcumin, a poorly water-soluble drug, has been carried out by the liquid antisolvent technique in the presence of ultrasound and stabilizers. Curcumin particles with varied morphology were observed to have formed during precipitation in the presence of ultrasound and additives such as sodium dodecyl sulfate (SDS), Tween 80, hydroxyl propyl methylcellulose (HPMC), polyvinyl pyrrolidone (PVP), and bovine serum albumin (BSA). Characterization of the precipitated particles reveals that curcumin particles precipitated with ultrasound and large polymeric stabilizers such as HPMC, PVP, and BSA are superstructures formed by aggregation of several primary curcumin nanoparticles. The particles in these cases appeared to be loose aggregates (of ~1-5 μm in size) composed of several curcumin nanoparticles (~50-200 nm in size). On the other hand, curcumin particles precipitated in the presence of ultrasound and without additive as well as small-molecule stabilizers like SDS and Tween 80 appear more fused (the primary building blocks of these particles were not clearly visible). Moreover, curcumin particles precipitated in the presence of ultrasound only and particles precipitated in the presence of ultrasound along with additives were found to exist in the orthorhombic form, whereas raw curcumin and curcumin particles precipitated without any additive and without ultrasound were found to exist in the monoclinic form. The results obtained in this work suggest that curcumin particles with the desired physical form and morphology can be engineered through a careful manipulation/choice of ultrasound and additives during precipitation. This journal is