Freeze dried multicomponent inclusion complexes of quercetin: Physicochemical evaluation and pharmacodynamic study
Freeze dried multicomponent inclusion complexes of quercetin: Physicochemical evaluation and pharmacodynamic study
The present study was undertaken to investigate the effect of cyclodextrin (CD) complexation in presenceof hydrophilic polymer on physicochemical properties as well as anti- inflammatory activity of quercetin (QUN). Theinitial phase solubility studies were carried out in presence and absence of hydrophilic polymers(hydroxypropylmethylcellulose, polyvinylpyrrolidone K30 and poloxamer 188) to study their effect on the stability andcomplexation efficiency of CDs. The binary (QUN-βCD and QUN-HPβCD) and multicomponent (QUN-βCD-POLOand QUN-HPβCD-POLO) inclusion complexes of QUN prepared using lyophilization technique. The complexes weresubjected to DSC, ATR-FTIR, XRPD and SEM analysis, and evaluated for drug content and saturation solubility. Thephase solubility studies revealed the formation of QUN-βCD and QUN-HPβCD complexes with 1:1 stoichiometry. Theincorporation of POLO increased the stability as well as complexation efficiency of CDs. FTIR and DSC analysisindicated hydrogen bonding interaction POLO with QUN and CDs. XRD and SEM analysis revealed greateramorphization in case of multicomponent inclusion complexes. All complexes showed uniform drug content. QUNHPβCD-POLO exhibited maximum solubility than the physical mixtures and other complexes. The pure QUN andQUN-HPβCD-POLO were tested for in vivo anti-inflammatory activity by Carrageenan induced rat paw edema method.QUN-HPβCD-POLO exhibited significant increase in anti-inflammatory activity as compared to pure QUN.
___
- [1] Borghetti GS, Lula IS, Sinisterra RD, Bassani VL. Quercetin/β-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture. AAPS PharmSciTech. 2009;10(1):235–242. [CrossRef]
- [2] Zheng Y, Haworth IS, Zuo Z, Chow MSS, Chow AHL. Physicochemical and structural characterization of quercetinbeta- cyclodextrin complexes. J Pharm Sci. 2005;94(5):1079–1089. [CrossRef]
- [3] Jullian C, Moyano L, Yañez C, Olea-Azar C. Complexation of quercetin with three kinds of cyclodextrins: An antioxidant study. Spectrochim Acta - Part A Mol Biomol Spectrosc. 2007;67(1):230–234. [CrossRef]
- [4] Anand David A, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev. 2016;10(20):84-89. [CrossRef]
- [5] Pralhad T, Rajendrakumar K. Study of freeze-dried quercetin-cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. J Pharm Biomed Anal. 2004;34(2):333–339. [CrossRef]
- [6] Li H, Zhao X, Ma Y, Zhai G, Li L, Lou H. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Control Release. 2009;133(3):238–244. [CrossRef]
- [7] Penalva R, González-Navarro CJ, Gamazo C, Esparza I, Irache JM. Zein nanoparticles for oral delivery of quercetin: Pharmacokinetic studies and preventive anti-inflammatory effects in a mouse model of endotoxemia. Nanomedicine. 2017;13(1):103–110. [CrossRef]
- [8] Jadhav P, Petkar B, Pore Y, Kulkarni A, Burade K. Physicochemical and molecular modeling studies of cefixime–larginine– cyclodextrin ternary inclusion compounds. Carbohydr Polym. 2013;98(2):1317–1325. [CrossRef]
- [9] Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85(10):1017–1025. [CrossRef]
- [10] Loftsson T, Masson M. Cyclodextrins in topical drug formulations: Theory and practice. Int J Pharm. 2001;225(1– 2):15–30. [CrossRef]
- [11] Jadhav P, Pore Y. Physicochemical, thermodynamic and analytical studies on binary and ternary inclusion complexes of bosentan with hydroxypropyl-β-cyclodextrin. Bull Fac Pharm Cairo Univ. 2016;55(1):147–154. [CrossRef]
- [12] Redenti E, Szente L, Szejtli J. Drug/cyclodextrin/hydroxy acid multicomponent systems. Properties and pharmaceutical applications. J Pharm Sci. 2000;89(1):1–8. [CrossRef]
- [13] Gajare P, Patil C, Kalyane N, Pore Y. Effect of hydrophilic polymers on pioglitazone complexation with hydroxypropyl-β-cyclodextrin. Dig J Nanomater Biostruct. 2009;4(4):891–897.
- [14] Pokharkar V, Khanna A, Venkatpurwar V, Dhar S, Mandpe L. Ternary complexation of carvedilol, beta-cyclodextrin and citric acid for mouth-dissolving tablet formulation. Acta Pharm. 2009;59(2):121–132. [CrossRef]
- [15] Davis M, Brewster M. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov. 2004;3:1023–1035. [CrossRef]
- [16] Higuchi T, Connors K. Phase solubility techniques. Adv Anal Chem Instr. 1965;117–212.
- [17] Shah M, Pore Y, Dhawale S, Burade K, Kuchekar B. Physicochemical characterization of spray dried ternary microcomplexes of cefuroxime axetil with hydroxypropyl-β-cyclodextrin. J Incl Phenom Macrocycl Chem. 2013;76:391– 401. [CrossRef]
- [18] Valero M, Pérez-Revuelta BI, Rodríguez LJ. Effect of PVP K-25 on the formation of the naproxen:β-cyclodextrin complex. Int J Pharm. 2003;253(1–2):97–110. [CrossRef]
- [19] Katzhendler I, Azoury R, Friedman M. Crystalline properties of carbamazepine in sustained release hydrophilic matrix tablets based on hydroxypropyl methylcellulose. J Control Release. 1998;54(1):69–85. [CrossRef]
- [20] Sinha V, Anitha R, Ghosh S, Nanda A, Kumria R. Complexation of celecoxib with β-cyclodextrin: Characterization of the interaction in solution and in solid state. J Pharm Sci. 2005;94:676–687. [CrossRef]
- [21] Loftsson T, Frikdriksdóttir H, Sigurkdardóttir AM, Ueda H. The effect of water-soluble polymers on drugcyclodextrin complexation. Int J Pharm. 1994; 110(2):169-177. [CrossRef]
- [22] Bodratti A, Alexandridis P. Formulation of poloxamers for drug delivery. J Funct Biomater. 2018;9(1):pii E11. [CrossRef]
- [23] Koontz JL, Marcy JE, O’Keefe SF, Duncan SE. Cyclodextrin inciusion complex formation and solid-state characterization of the natural antioxidants α-tocopherol and quercetin. J Agric Food Chem. 2009;57(4):1162–1171. [CrossRef]
- [24] Srivalli KMR, Mishra B. Improved aqueous solubility and antihypercholesterolemic activity of ezetimibe on formulating with hydroxypropyl-β-cyclodextrin and hydrophilic auxiliary substances. AAPS PharmSciTech. 2016;17(2):272–283. [CrossRef]
- [25] Yadav VR, Suresh S, Devi K, Yadav S. Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model. AAPS PharmSciTech. 2009;10(3):752–762. [CrossRef]
- [26] El-Maradny H, Mortada S, Kamel O, Hikal A. Characterization of ternary complexes of meloxicam-HPβCD and PVP or L-arginine prepared by the spray-drying technique. Acta Pharm. 2008;58(4):455–466. [CrossRef]
- [27] Chourasiya A, Upadhayay A, Shukla RN. Isolation of quercetin from the leaves of Azardirachta indica and antidiabetic study from the crude extracts. J Pharm Biomed Sci. 2012;25(25):179–181.
- [28] Zou A, Zhao X, Handge UA, Garamus VM, Willumeit-Römer R, Yin P. Folate receptor targeted bufalin/β- cyclodextrin supramolecular inclusion complex for enhanced solubility and anti-tumor efficiency of bufalin. Mater Sci Eng C. 2017;78:609–618. [CrossRef]
- [29] Bulani VD, Kothavade PS, Kundaikar HS, Gawali NB, Chowdhury AA, Degani MS, Juvekar AC. Inclusion complex of ellagic acid with β-cyclodextrin: Characterization and in vitro anti-inflammatory evaluation. J Mol Struct. 2016;1105:308–315. [CrossRef]
- [30] Brewster M, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007;59:645–666. [CrossRef]
- [31] Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Exp Biol Med. 1962;111:544–547. [CrossRef]
- [32] Kaidama WM, Gacche RN. Anti-inflammatory activity of quercetin in acute and chronic phases of inflammation in Guinea pigs. Am J Phytomed Clin Ther 2015;3(2):129-136.