Preparation and characterization of quercetin nanocrystals.

This study is to enhance the dissolution rate of a poorly water-soluble drug, quercetin, by fabricating nanocrystals using high-pressure homogenization. The particle size, crystallinity, dissolution, and antioxidant effects of fabricated quercetin nanocrystals have been investigated. Characterization of the original quercetin powder and nanocrystals was carried out by photon correlation spectroscopy (PCS), laser diffraction, scanning electron microscopy, differential scanning calorimetry (DSC), X-ray diffraction, dissolution tester, and so on. A PCS size of about 483 nm was obtained for the nanocrystals after 20 cycles of homogenization at 1500 bar. X-ray diffraction and DSC studies revealed that the lyophilized quercetin nanoparticles were crystalline after high-pressure homogenization. The percent dissolution efficiency, relative dissolution, mean dissolution time, difference factor (f(1)), and similarity factor (f(2)) were calculated for the statistical analysis. It was found that the dissolution of the drug nanocrystals was much higher than that of the pure drug at pH 6.8 and 1.2. The antioxidant activity and reducing power of the quercetin nanocrystals were more effective than the original quercetin.

[1]  A. C. Eissens,et al.  The Effect of Parenterally Administered Cyclodextrins on Cholesterol Levels in the Rat , 2004, Pharmaceutical Research.

[2]  Xiaomei Mu,et al.  Preparation and properties of poly(vinyl alcohol)-stabilized liposomes. , 2006, International journal of pharmaceutics.

[3]  Guohua Chen,et al.  Role of Freeze Drying in Nanotechnology , 2007 .

[4]  Bruno C. Hancock,et al.  Characteristics and significance of the amorphous state in pharmaceutical systems. , 1997, Journal of pharmaceutical sciences.

[5]  R. Müller,et al.  Development of ascorbyl palmitate nanocrystals applying the nanosuspension technology. , 2008, International journal of pharmaceutics.

[6]  C. Kandaswami,et al.  The antitumor activities of flavonoids. , 2005, In vivo.

[7]  Y. Wang,et al.  Fabrication of drug nanoparticles by evaporative precipitation of nanosuspension. , 2010, International journal of pharmaceutics.

[8]  W. Regelson,et al.  Review of the biology of Quercetin and related bioflavonoids. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[9]  P. Jain,et al.  In vitro antioxidant activity and phenolic content of Croton caudatum. , 2009 .

[10]  J. Sousa,et al.  Influence of cellulose ether polymers on ketoprofen release from hydrophilic matrix tablets. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[11]  Donald L. Wise,et al.  Nanosuspensions: A Formulation Approach for Poorly Soluble and Poorly Bioavailable Drugs , 2000 .

[12]  Oded Shoseyov,et al.  Rapid liquid chromatography-ultraviolet determination of organic acids and phenolic compounds in red wine and must. , 2004, Journal of chromatography. A.

[13]  M. Comalada,et al.  In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway , 2005, European journal of immunology.

[14]  M. Lawrence,et al.  Microemulsion-based media as novel drug delivery systems , 2000 .

[15]  Z. Zuo,et al.  Physicochemical and structural characterization of quercetin-beta-cyclodextrin complexes. , 2005, Journal of pharmaceutical sciences.

[16]  D. Bikiaris,et al.  Dissolution enhancement of flavonoids by solid dispersion in PVP and PEG matrixes: A comparative study , 2006 .

[17]  Chao Jianbin,et al.  Preparation and spectral investigation on inclusion complex of β-cyclodextrin with rutin , 2003 .

[18]  Peter C. H. Hollman,et al.  Optimization of a quantitative HPLC determination of potentially anticarcinogenic flavonoids in vegetables and fruits , 1992 .

[19]  S. G. Leitão,et al.  Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method , 2001, Phytotherapy research : PTR.

[20]  Kelly E Heim,et al.  Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. , 2002, The Journal of nutritional biochemistry.

[21]  B. Subramaniam,et al.  Pharmaceutical processing with supercritical carbon dioxide. , 1997, Journal of pharmaceutical sciences.

[22]  J. Carstensen,et al.  Solid State Stability , 2000 .

[23]  H. Hung,et al.  Analysis of drug dissolution data. , 1999, Statistics in medicine.

[24]  Qiang Zhang,et al.  In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery , 2010, Nanotechnology.

[25]  G. Liversidge,et al.  Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats , 1995 .

[26]  B. Ye,et al.  Liposomal Quercetin Efficiently Suppresses Growth of Solid Tumors in Murine Models , 2006, Clinical Cancer Research.

[27]  Rainer H Müller,et al.  Production and characterization of Hesperetin nanosuspensions for dermal delivery. , 2009, International journal of pharmaceutics.

[28]  P. Chattopadhyay,et al.  Production of griseofulvin nanoparticles using supercritical CO(2) antisolvent with enhanced mass transfer. , 2001, International journal of pharmaceutics.

[29]  Chun-ching Lin,et al.  Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticles. , 2008, International journal of pharmaceutics.

[30]  A. Noyes,et al.  The rate of solution of solid substances in their own solutions , 1897 .

[31]  V. Villari,et al.  The rutin/beta-cyclodextrin interactions in fully aqueous solution: spectroscopic studies and biological assays. , 2005, Journal of pharmaceutical and biomedical analysis.

[32]  Tayade Pralhad,et al.  Study of freeze-dried quercetin-cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. , 2004, Journal of pharmaceutical and biomedical analysis.

[33]  P. Costa,et al.  Modeling and comparison of dissolution profiles. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[34]  B. Dupont Overview of the lipid formulations of amphotericin B. , 2002, The Journal of antimicrobial chemotherapy.

[35]  S. Guterres,et al.  Protective properties of melatonin-loaded nanoparticles against lipid peroxidation. , 2005, International journal of pharmaceutics.

[36]  M. Nakano Places of emulsions in drug delivery. , 2000, Advanced drug delivery reviews.

[37]  L. Öner,et al.  Evaluation of in Vitro Dissolution Profile Comparison Methods of Immediate Release Gliclazide Tablet Formulations , 2005 .

[38]  H. Govers,et al.  Micellar solubility and micelle/water partitioning of polychlorinated biphenyls in solutions of sodium dodecyl sulfate. , 1995, Environmental science & technology.

[39]  R. Müller,et al.  Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. , 2001, Advanced drug delivery reviews.