Preparation and characterization of micronized artemisinin via a Rapid Expansion of Supercritical Solutions (RESS) Method.

The particle sizes of pharmaceutical substances are important for their bioavailability. Bioavailability can be improved by reducing the particle size of the drug. In this study, artemisinin was micronized by the rapid expansion of supercritical solutions (RESS). The particle size of the unprocessed white needle-like artemisinin particles was 30 to 1200 µm. The optimum micronization conditions are determined as follows: extraction temperature of 62 °C, extraction pressure of 25 MPa, precipitation temperature 45 °C and nozzle diameter of 1000 µm. Under the optimum conditions, micronized artemisinin with a (mean particle size) MPS of 550 nm is obtained. By analysis of variance (ANOVA), extraction temperature and pressure have significant effects on the MPS of the micronized artemisinin. The particle size of micronized artemisinin decreased with increasing extraction temperature and pressure. Moreover, the SEM, LC-MS, FTIR, DSC and XRD allowed the comparison between the crystalline initial state and the micronization particles obtained after the RESS process. The results showed that RESS process has not induced degradation of artemisinin and that processed artemisinin particles have lower crystallinity and melting point. The bulk density of artemisinin was determined before and after RESS process and the obtained results showed that it passes from an initial density of 0.554 to 0.128 g·cm(-3) after the processing. The decrease in bulk density of the micronized powder can increase the liquidity of drug particles when they are applied for medicinal preparations. These results suggest micronized powder of artemisinin can be of great potential in drug delivery systems.

Preparation and physicochemical properties of 10-hydroxycamptothecin (HCPT) nanoparticles by supercritical antisolvent (SAS) process.

The goal of the present work was to study the feasibility of 10-hydroxycamptothecin (HCPT) nanoparticle preparation using supercritical antisolvent (SAS) precipitation. The influences of various experimental factors on the mean particle size (MPS) of HCPT nanoparticles were investigated. The optimum micronization conditions are determined as follows: HCPT solution concentration 0.5 mg/mL, the flow rate ratio of CO(2) and HCPT solution 19.55, precipitation temperature 35 °C and precipitation pressure 20 MPa. Under the optimum conditions, HCPT nanoparticles with a MPS of 180 ± 20.3 nm were obtained. Moreover, the HCPT nanoparticles obtained were characterized by Scanning electron microscopy, Dynamic light scattering, Fourier-transform infrared spectroscopy, High performance liquid chromatography-mass spectrometry, X-ray diffraction and Differential scanning calorimetry analyses. The physicochemical characterization results showed that the SAS process had not induced degradation of HCPT. Finally, the dissolution rates of HCPT nanoparticles were investigated and the results proved that there is a significant increase in dissolution rate compared to unprocessed HCPT.

A novel preparation method for camptothecin (CPT) loaded folic acid conjugated dextran tumor-targeted nanoparticles.

In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy.

Insulin nanoparticles for transdermal delivery: preparation and physicochemical characterization and in vitro evaluation.

AIM: This work is aimed to study the feasibility of insulin nanoparticles for transdermal drug delivery (TDD) using supercritical antisolvent (SAS) micronization process. METHODS: The influences of various experimental factors on the mean particle size (MPS) of insulin nanoparticles were investigated. Moreover, the insulin nanoparticles obtained were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric (TG) analyses. RESULTS: Under optimum conditions, uniform spherical insulin nanoparticles with a MPS of 68.2 +/- 10.8 nm were obtained. The Physicochemical characterization results showed that SAS process has not induced degradation of insulin. Evaluation in vitro showed that insulin nanoparticles were accorded with the Fick's first diffusion law and had a high permeation rate. CONCLUSION: These results suggest that insulin nanoparticles can have a great potential in TDD systems of diabetes chemotherapy.

Determination of paclitaxel and its analogues in the needles of Taxus species by using negative pressure cavitation extraction followed by HPLC-MS-MS.

A new separation method, negative pressure cavitation (NPC) extraction followed by HPLC-MS-MS for the determination of paclitaxel and its analogues in the needles of Taxus species is described in this study. Compared with three conventional extraction methods, NPC is a more effective, economical, and facile method for the separation of nature compounds from herbal plants. In contrast to high-temperature extraction, NPC at low temperature can minimize undesirable reactions such as thermal decomposition or degradation. In addition, the extraction mechanism of NPC was also illuminated. The effects of vacuum degree, extraction solvent, ratio of solid to liquid, time, and times extraction were studied and optimized. The optimum extraction conditions were as follows: vacuum degree -0.03 MPa, solvent 80% v/v alcohol, ratio of material to liquid 1:15 (g/mL), extraction time 60 min, extraction (x3). Using these conditions, the recoveries of 10-deacetyl-7-xylosylpaclitaxel, 10-deacetylpaclitaxel, cephalomannine, and paclitaxel were higher than 95.88, 95.82, 94.85, and 96.18%, respectively. The contents of paclitaxel, 10-deacetyl-7-xylosylpaclitaxel, 10-deacetylpaclitaxel, and cephalomannine for Taxus chinensis were 0.0053, 0.0467, 0.0132, and 0.0076%, and 0.0067, 0.0153, 0.0047, and 0.0064% for Taxus cuspidata, respectively. Furthermore, a comparison of SEM images observed the morphological changes of microstructures and cellular damage in yew needles.

In vitro and in vivo evaluation of camptothecin nanosuspension: a novel formulation with high antitumor efficacy and low toxicity.

The purpose of this study was to evaluate the in vitro and in vivo antitumor efficacy and the dose dependent toxicity of camptothecin nanosuspension (Nano-CPT) comparing with that of topotecan (TPT). A novel supercritical antisolvent (SAS) process-high pressure homogenization technique has been developed to prepare Nano-CPT. The cytotoxicity of Nano-CPT and TPT was investigated against MCF-7, HCT-8, and PC-3 cell lines using MTT assay, antitumor activity in vivo were evaluated against HCT-8 xenograft model, and the dose dependent toxicity in vivo during the treatment were investigated by body weight changes and relative organ weight variations. The Nano-CPT presents about 6 times in vitro cytotoxicity active than TPT against cell lines MCF-7, nearly the same in vivo antitumor activity with TPT and lower toxicity. The results confirm that Nano-CPT is a novel potential formulation with high antitumor efficacy and low toxicity.

Negative-pressure cavitation extraction for the determination of flavonoids in pigeon pea leaves by liquid chromatography-tandem mass spectrometry.

A new method, namely negative-pressure cavitation extraction (NPCE), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is presented for the extraction and quantification of flavonoids in pigeon pea leaves. This method combines the high efficiency of NPCE and the sensitivity and accuracy of MS/MS. The influential parameters of the NPCE procedure including liquid/solid ratio, extraction time, nitrogen flow and number of extraction cycles were optimized. Under optimized conditions, the efficiency of NPCE for extracting five flavonoids was compared to microwave-assisted extraction (MAE), ultrasonic extraction (USE) and heating reflux extraction (HRE). Additionally, structural disruption to pigeon pea leaves samples with different extraction methods was investigated by scanning electron microscopy. The relative recovery with NPCE was equivalent to or higher than that with USE and obviously higher than those with MAE and HRE which are usually conducted in higher temperatures. Furthermore, because NPCE was performed with nitrogen at room temperature, the degradation and oxidation of analytes were avoided. In addition, the NPCE method was validated in terms of repeatability and reproducibility, relative standard deviation for relative recovery was lower than 5.84 and 8.83%, respectively. The method was also successfully applied for the quantification of five flavonoids in pigeon pea leaves. All these results suggest that the developed NPCE-LC-MS/MS method represents an excellent alternative for the extraction and quantification of flavonoids in other plant materials.