Ghanem et al . / IJDFR volume 3 Issue 6, Nov-Dec .2012 68 Ghanem et al / IJDFR volume 3 Issue 6, Nov-Dec .2012 Available online at www.ordonearresearchlibrary.org ISSN 2229-5054 INTERNATIONAL JOURNAL OF DRUG FORMULATION AND RESEARCH SOLUBILITY AND DISSOLUTION ENHANCEMENT OF QUERCETIN VIA PREPARATION OF ROTARY SOLVENT EVAPORATED AND FREEZE DRIED TERNARY SOLID DISPERSIONS Ahmed Shawky Mohamed Ghanem*, Dr. Hany Saleh Mohamed Ali, Dr. Sohair Mostafa El-Shanawany, Dr. El-Sayed Ali Ibrahim Faculty of Pharmacy, Assiut University, Egypt. Received: 11 Oct. 2012; Revised: 5 Nov. 2012; Accepted: 12 Dec. 2012; Available online: 5 Jan. 2013 INTRODUCTION Quercetin [QC] is one of the most prominent antioxidants [1]. In spite of its wide spectrum of bioactivity including antiviral [2], anticancer [3], antiinflammatory [4] and hepatoprotective actions [5], its therapeutic benefits is still limited because of its poor bioavailability [6] due to its poor solubility and limited dissolution [7]. Therefore, an efficient oral formulation of QC with an enhanced dissolution rate and hence, an improved bioavailability is highly desired. Various techniques have been used in an attempt to improve solubility and dissolution rates of poorly soluble drugs which includes solid dispersion, micronization, lipid based formulations, liquisolid compacts, and complexation [16]. Lately, a few attempts to enhance QC bioavailability have been reported in the literature. Indeed, it was proven that QC dissolution rate could be enhanced by complexation with cyclodextrins [17], development of biodegradable nanoparticles [18], and preparation of QC liposomes [19]. However, instability problem implicates the usefulness of these preparations. The solid dispersion technique for water-insoluble drugs provides an efficient method to improve the dissolution rate of such drugs [20,21]. In solid dispersion systems, a drug may exist as an amorphous form in Research Article ABSTRACT Quercetin (QC), a naturally occurring antioxidant drug has wide range of pharmacological activities. However, its limited aqueous solubility and dissolution restrict its bioavailability. Ternary solid dispersions (TSD) of QC in different ratios with hydrophilic carriers such as PVP K30 and PF 127 were prepared by freeze drying (FTSD) and rotary solvent evaporation (RTSD) techniques. The prepared dispersions were evaluated for solubility and dissolution in comparison to that of their physical mixtures and the drug powder. The aqueous solubility of QC powder was favored by formation of TSD with polyvinylpyrrolidone K30 (PVP K30) and pluronic F 127(PF 127), and improved from 7.6 ± 0.8 mg/l for QC to 256 ± 4.0 and 240 ± 0.75 mg/l for RTSD and FTSD respectively. The high solubility of QC from TSD could contribute to the enhanced dissolution, as the percent of QC dissolved at 300 min. (% D 300min ) increased from 33 for QC to 96.74 for RTSD and 85.9 for FTSD. Solid state characterization of TSD system using XRPD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, thus accounting for enhancement in dissolution rate. Keywords: Ternary solid dispersions, quercetin, freeze drying, solvent evaporation, dissolution, solubility.
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Ghanem et al . / IJDFR volume 3 Issue 6, Nov-Dec .2012
68 Ghanem et al / IJDFR volume 3 Issue 6, Nov-Dec .2012
Available online at www.ordonearresearchlibrary.org ISSN 2229-5054
INTERNATIONAL JOURNAL OF DRUG FORMULATION AND RESEARCH
SOLUBILITY AND DISSOLUTION ENHANCEMENT OF QUERCETIN VIA PREPARATION OF ROTARY SOLVENT EVAPORATED AND FREEZE DRIED TERNARY SOLID DISPERSIONS
Ahmed Shawky Mohamed Ghanem*, Dr. Hany Saleh Mohamed Ali, Dr. Sohair Mostafa El-Shanawany, Dr.
El-Sayed Ali Ibrahim Faculty of Pharmacy, Assiut University, Egypt.
Quercetin [QC] is one of the most prominent antioxidants [1]. In spite of its wide spectrum of
bioactivity including antiviral [2], anticancer [3], antiinflammatory [4] and hepatoprotective actions [5], its
therapeutic benefits is still limited because of its poor bioavailability [6] due to its poor solubility and
limited dissolution [7]. Therefore, an efficient oral formulation of QC with an enhanced dissolution rate and
hence, an improved bioavailability is highly desired.
Various techniques have been used in an attempt to improve solubility and dissolution rates of poorly
soluble drugs which includes solid dispersion, micronization, lipid based formulations, liquisolid compacts, and
complexation [16]. Lately, a few attempts to enhance QC bioavailability have been reported in the literature.
Indeed, it was proven that QC dissolution rate could be enhanced by complexation with cyclodextrins [17],
development of biodegradable nanoparticles [18], and preparation of QC liposomes [19]. However, instability
problem implicates the usefulness of these preparations.
The solid dispersion technique for water-insoluble drugs provides an efficient method to improve the
dissolution rate of such drugs [20,21]. In solid dispersion systems, a drug may exist as an amorphous form in
Research Article
ABSTRACT Quercetin (QC), a naturally occurring antioxidant drug has wide range of pharmacological activities. However, its limited aqueous solubility and dissolution restrict its bioavailability. Ternary solid dispersions (TSD) of QC in different ratios with hydrophilic carriers such as PVP K30 and PF 127 were prepared by freeze drying (FTSD) and rotary solvent evaporation (RTSD) techniques. The prepared dispersions were evaluated for solubility and dissolution in comparison to that of their physical mixtures and the drug powder. The aqueous solubility of QC powder was favored by formation of TSD with polyvinylpyrrolidone K30 (PVP K30) and pluronic F 127(PF 127), and improved from 7.6 ± 0.8 mg/l for QC to 256 ± 4.0 and 240 ± 0.75 mg/l for RTSD and FTSD respectively. The high solubility of QC from TSD could contribute to the enhanced dissolution, as the percent of QC dissolved at 300 min. (% D300min) increased from 33 for QC to 96.74 for RTSD and 85.9 for FTSD. Solid state characterization of TSD system using XRPD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, thus accounting for enhancement in dissolution rate. Keywords: Ternary solid dispersions, quercetin, freeze drying, solvent evaporation, dissolution, solubility.
Ghanem et al . / IJDFR volume 3 Issue 6, Nov-Dec .2012
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polymeric carriers such as PVP and pluronics® , and this may result in improved solubility and dissolution rate
as compared with crystalline material. The mechanisms for the enhancement of the dissolution rate of solid
dispersions have been proposed by several investigators. Drugs molecularly dispersed in polymeric carriers may
achieve the highest levels of particle size reduction and surface area enhancement, which result in improved
dissolution rates [22]. Furthermore, drug solubility and wettability may be increased by surrounding hydrophilic
carriers [23].
Freeze drying also known as lyophilization has been thought of as a molecular mixing technique
where the drug and carrier were co-dissolved in common solvent, frozen and then sublimed under vacuum
to obtain a lyophilized molecular dispersion [24].
The present study aimed to improve the solubility and dissolution of QC, a poorly soluble
bioflavonoid, via dispersion of the drug through the matrices of various hydrophilic carrier systems using
rotary solvent evaporation and freeze drying techniques.