Effect of high pressure homogenization on physicochemical properties of curcumin nanoparticles prepared by...

Dissolution enhancement of poorly water soluble drugs is a major challenge in pharmaceutical industry. The aim of this study is to fabricate curcumin nanoparticles by antisolvent crystallization in the presence of PVP-K30 or HPMC with various concentrations as a stabilizer. The effect of high pressure homogenization on properties of curcumin particles is also investigated in this study. The antisolvent crystallization method followed by freeze drying (CRS-FD) and also antisolvent crystallization and high pressure homogenization followed by freeze drying (HPH-FD) were employed to modify curcumin particles. Physical mixtures of the drug and additives were also prepared for comparison purposes. The solid state analysis (DSC, XRPD and FT-IR studies), particle size measurement, morphological analysis, saturation solubility and dissolution behavior of the samples were investigated. The curcumin crystallized without using stabilizer produced polymorph 2 curcumin with lower crystallinity and higher solubility. The samples obtained in the presence of stabilizers showed higher solubility compared to its physical mixtures counterpart. It was found that the stabilizers used in the current study were capable of inhibiting the crystal growth of particles during crystallization. High pressure homogenizer method generated smaller particles compared to those samples that were not subjected to high pressure homogenizer (for example, 2748 nm for 5% PVP CRS-FD sample and 706 nm for 5% PVP HPH-FD sample). Particles obtained via HPH showed better solubility and dissolution rate compared to those samples that HPH was not employed (for example, the saturated solubility of 25% PVP CRS-FD sample was near 2 μg/ml while this amount was approximately 4.3 μg/ml for 25% HPH-FD sample. The effect of high pressure homogenization on dissolution rate is more pronounced for samples with lower stabilizer ratio. The samples prepared with high pressure homogenizer using 50% PVP showed 25-fold higher solubility compared to untreated curcumin. Generally, it can be concluded that the method of preparation, selection of suitable stabilizer and concentration of stabilizer play a critical role on particle size and dissolution rate of curcumin.