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

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.

Homayouni A ，Sohrabi M ，Amini M ，Varshosaz J ，Nokhodchi A ... -  《-》

Comparing various techniques to produce micro/nanoparticles for enhancing the dissolution of celecoxib containing PVP.

One of the major challenges in pharmaceutical development is the poor dissolution performance of drugs. Celecoxib (CLX) is a poorly water soluble drug with its bioavailability being limited by its poor dissolution. In this study several particle engineering methods were employed on CLX using various ratios of CLX:PVP-K30. Micro/nanoparticles of CLX:PVP were prepared by using spray drying (SD), antisolvent crystallization followed by freeze drying (CRS-FD) and spray drying (CRS-SD) techniques. The suspension obtained through antisolvent crystallization was also subjected to high pressure homogenization followed by freeze drying (HPH-FD). Particle size measurements, saturation solubility, optical and scanning electron microscopy, DSC, XRPD, FT-IR and dissolution test were performed to characterize the physicochemical and pharmaceutical properties of the samples. The results showed that spray dried samples in the presence of (50%) PVP produced spherical particles and exhibited a high dissolution rate. Interestingly in the antisolvent crystallization technique, spherical nanoparticles of drug-PVP were obtained in the range of 291-442 nm. The average particle size was dependent on the concentration of the PVP used during the crystallization process. Solid state analysis showed that these particles were completely amorphous in nature. Also interesting to note was that at concentration of 5% PVP, when the suspension of nanoparticles was subjected to the high pressure homogenization process, the crystallinity of CLX increased. Despite the partial crystallinity of particles produced, they showed excellent dissolution behavior. It can thus be concluded that the method of preparation of CLX micro/nanoparticles had a big impact on the dissolution rate when the concentration of PVP was low (e.g., 5%). At high PVP concentration (e.g., 50%) all methods used to prepare engineered CLX particles showed better dissolution with no significant differences in their dissolution efficiency.

Homayouni A ，Sadeghi F ，Varshosaz J ，Garekani HA ，Nokhodchi A ... -  《-》

Curcumin nanoparticles containing poloxamer or soluplus tailored by high pressure homogenization using antisolvent crystallization.

Curcumin is a natural active constituent of Curcuma longa from Zingiberaceae family that shows many different pharmacological effects such as anticancer, antioxidant, anti-inflammatory, antimicrobial and antiviral effect. However, its bioavailability is profoundly limited by its poor water solubility. In this study antisolvent crystallization followed by freeze drying was used for the preparation of curcumin nanoparticles. The presence of different ratios of hydrophilic polymers (poloxamer 188 & soluplus) on physicochemical properties of curcumin nanoparticles was also investigated. In addition, the effect of high pressure homogenization (HPH) on solubility and dissolution properties of curcumin was investigated. All nanoparticle formulations were examined to determine their particle size distribution, saturation solubility, morphology (SEM), solid state (DSC, XRPD and FT-IR) and dissolution behavior. It was observed that curcumin crystallized in the presence of polymers exhibited better solubility and dissolution rate in comparison with original curcumin. The results showed that the concentration of the stabilizer and the method used to prepare nanoparticles can control the dissolution of curcumin. The crystallized nanoparticles showed polymorph 2 curcumin with lower crystallinity and higher dissolution rate. Curcumin nanoparticles containing 50% soluplus prepared via HPH method presented 16-fold higher solubility than its original form. In conclusion, samples crystalized and proceed with HPH technique showed smaller particle size, better re-dispersibility, higher solubility and dissolution rate in water compared with a sample prepared using a simple antisolvent crystallization process.

Homayouni A ，Amini M ，Sohrabi M ，Varshosaz J ，Nokhodchi A ... -  《-》

Antisolvent precipitation technique: A very promising approach to crystallize curcumin in presence of polyvinyl pyrrolidon for solubility and dissolution enhancement.

Curcumin with a vast number of pharmacological activities is a poorly water soluble drug which its oral bioavailability is profoundly limited by its dissolution or solubility in GI tract. Curcumin could be a good anticancer drug if its solubility could be increased. Therefore, the aim of the present study was to increase the dissolution rate of curcumin by employing antisolvent crystallization technique and to investigate the effect of polyvinyl pyrrolidone K30 (PVP) as colloidal particles in crystallization medium on resultant particles. Curcumin was crystalized in the presence of different amounts of PVP by antisolvent crystallization method and their physical mixtures were prepared for comparison purposes. The samples were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The solubility and dissolution of the treated and untreated curcumin were also determined. Antisolvent crystallization of curcumin led to the formation of particles with no definite geometric shape. It was interesting to note that the DSC and XRPD studies indicated the formation of a new polymorph and less crystallinity for particles crystallized in the absence of PVP. However, the crystallized curcumin in the presence of PVP was completely amorphous. All crystalized curcumin samples showed much higher dissolution rate compared to untreated curcumin. The amount of curcumin dissolved within 10 for treated curcumin in the presence of PVP (1:1 curcumin:PVP) was 7 times higher than untreated curcumin and this enhancement in the dissolution for curcumin samples crystallized in the absence of PVP was around 5 times. Overall' the results of this study showed that antisolvent crystallization method in the absence or presence of small amounts of PVP is very efficient in increasing the dissolution rate of curcumin to achieve better efficiency for curcumin.

Sadeghi F ，Ashofteh M ，Homayouni A ，Abbaspour M ，Nokhodchi A ，Garekani HA ... -  《-》

Promising dissolution enhancement effect of soluplus on crystallized celecoxib obtained through antisolvent precipitation and high pressure homogenization techniques.

Poor solubility and dissolution of hydrophobic drugs have become a major challenge in pharmaceutical development. Drug nanoparticles have been widely accepted to overcome this problem. The aim of this study was to manufacture celecoxib nanoparticles using antisolvent precipitation and high pressure homogenization techniques in the presence of varying concentrations of soluplus(®) as a hydrophilic stabilizer. Antisolvent crystallization followed by freeze drying (CRS-FD) and antisolvent crystallization followed by high pressure homogenization and freeze drying (HPH-FD) were used to obtain celecoxib nanoparticles. The obtained nanoparticles were analyzed in terms of particle size, saturation solubility, morphology (optical and scanning electron microscopy), solid state (DSC, XRPD and FT-IR) and dissolution behavior. The results showed that celecoxib nanoparticle can be obtained when soluplus was added to the crystallization medium. In addition, the results showed that the concentration of soluplus and the method used to prepare nanoparticles can control the size and dissolution of celecoxib. Samples obtained in the presence of 5% soluplus through HPH technique showed an excellent dissolution (90%) within 4min. It is interesting to note that celecoxib samples with high crystallinity showed better dissolution than those celecoxib samples with high amorphous content, although they had the same concentration of soluplus. DSC and XRPD proved that samples obtained via HPH technique are more crystalline than the samples obtained through only antisolvent crystallization technique.

Homayouni A ，Sadeghi F ，Varshosaz J ，Afrasiabi Garekani H ，Nokhodchi A ... -  《-》