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

Abstract

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. [6][7][8] DL-glutamic acid, 11 and 11102 | CrystEngComm, 2014, 16, 11102-11114 This journal is † Electronic supplementary information (ESI) available: Experimental materials and methods, table on precipitated curcumin form details, comparative XRPD patterns of form 1, form 2 and form 3 with the precipitated curcumin particles, hydrogen bonding in different curcumin forms, FTIR spectra of precipitated curcumin particles, and the SEM micrograph of raw curcumin. See

Effect of high pressure homogenization on physicochemical properties of curcumin nanoparticles prepared by antisolvent crystallization using HPMC or PVP

“…According to the hydrophobicity of CUR it could be predicted that the generated crystals could aggregate together and the crystals become large. This result has also been reported for CUR prepared with antisolvent crystallization [31,32]. Yadav and Kumar reported that curcumin nanocrystals could be prepared by antisolvent precipitation however these particles aggregated simply after a while in the absence of any stabilizer.…”

Curcumin nanosuspension: Screening for antioxidant and antibacterial activities and study of protein adsorption

“…The particle size and the particle morphology of CN and CNS at a curcumin concentration of 0.1 mg/ml was observed using SEM (Figure 1). The diameter size of most particles ranged from 200 to 300 nm and exhibited a rice seed-like morphology which was was similar to polymorphism of curcumin prepared by ultrasound and stabilizers from previous study (Thorat et al, 2014). As shown in Figure 1, the unmodified CN and modified CNS were comparable in size and particle morphology.…”

Solid-State Phase Transformations and Storage Stability of Curcumin Polymorphs

“…The particles precipitated with HPMC and ultrasound consisted of rice seed like particles ( Figure 12C−J) composed of aggregates of rod like primary nanoparticles. 26 The particle morphology remains the same and without much fusion of primary units even after 3 years of storage ( Figure 12K−N). Figure 13C−N presents SEM images of curcumin particles precipitated with ultrasound and PVP.…”