Abstract
Naringenin, a flavonoid specific to citrus fruits shows a variety of therapeutic effects like anti-inflammatory, anticarcinogenic, and antitumour effects. But it is associated with some limitations like poor water solubility, poor dissolution, lower half-life, and rapid clearance from the body. With the aim of improving amorphous nature, water solubility, and dissolution profile of naringenin and its complexes were prepared with β-cyclodextrin in three different molar ratios (1:1, 1:2, and 1:3) by solvent evaporation method. These complexes were characterized for solubility, drug content, chemical interaction (using FTIR), phase transition behavior (using DSC), crystallinity (using XRPD), surface morphology (using SEM), and in vitro dissolution study. The results were also critically compared with the results obtained from naringenin-phospholipid complexes (from author’s previous study). The prepared complexes showed high drug content (ranging from 69.53 to 84.38 %) and about two fold improvement in water solubility (from 41.81 to 76.31 μg mL−1 in the complex with 1:3 ratio). SEM of the complexes showed irregular and rough surface morphology. FTIR, DSC, and XRPD data confirmed the formation of the complex. Unlike the free naringenin which showed a total of only 48.78 % drug release at the end of 60 min, the complex showed 98.0–100 % in dissolution study. Thus it was concluded that the β-cyclodextrin of naringenin may be of potential use for improving bioavailability of poorly soluble phytoconstituents/herbal drugs. On critical comparison with the phospholipid complex of naringenin both the techniques were found almost equally effective in improving the solubility and the dissolution performance of naringenin in the complex form.
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Ortuño A, Garcia-Puig D, Fuster MD, Pérez ML, Sabater F, Porras I, Garcia-Lidon A, Del Rio AJ. Flavanone and nootkatone levels in different varieties of grapefruit and pummelo. J Agric Food Chem. 1995;43:1–5.
Kawaii S, Tomono Y, Katase E, Ogawa K, Yano M. Quantitation of flavonoids constituents in citrus fruits. J Agric Food Chem. 1999;47:3565–71.
Paganga G, Miller N, Rice-Evans C. The polyphenolic content of fruit and vegetables and their antioxidant activities: what does a serving constitute? Free Radic Res. 1999;30:153–62.
Middleton E, Kandaswami C. The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. In: Harborne JB, editor. The flavonoids: advances in research since 1986. London: Chapman and Hall; 1994. p. 619–52.
Benavente-Garcia O, Castillo J, Marin FR, Ortuño A, Del Rio JA. Uses and properties of citrus flavonoids. J Agric Food Chem. 1997;45:4505–15.
Montanari A, Chen J, Widmer W. Citrus flavonoids: a review of past biological activity against disease. Discovery of new flavonoids from Dancy tangerine cold pressed peel oil solids and leaves. In: Manthey, Buslig B, editors. Flavonoids in the living system. New York: Plenum; 1998. p. 103–16.
Ruh MF, Zacharewsky T, Connor K, Howell J, Chen I, Safe S. Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic activity. Biochem Phamacol. 1995;50:1485–93.
Miksicek RJ. Commonly occurring plant flavonoids have estrogenic activity. Mol Pharmacol. 1993;44:37–43.
Kuiper JM, Lemmen JG, Carlsson B, Corton JC, Safe SH, Van der Saag PT, Van der Burg B, Gustafsson JA. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinolology. 1998;139:4252–63.
Erlund I, Meririnne E, Alfthan G, Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr. 2001;131:235–41.
Semalty A, Semalty M, Rawat MSM. Essentials of Pharmaceutical Technology. Hyderabad: Pharma Med Press; 2011. p. 4–5.
Moneghini M, Kikig I, Perissutti B, Franceschinis E, Corteri A. Characterization of nimesulide-β-cyclodextrin system prepared by supercritical fluid impregnation. Eur J Pharm Bioparm. 2004;58:637–44.
Pralhad T, Kumar R. Study of freez-dried quercetin- cyclodextrin binary system by DSC, FTIR, X-ray diffraction and SEM analysis. J Pharm Biomed Anal. 2004;34:333–9.
Babu RJ, Pandit JK. Effect of cyclodextrin on the complexation and transdermal delivery of bupranolol through rat skin. Int J Pharm. 2004;271:155–65.
Rawat S, Jain SK. Solubility enhancement of celecoxib using β-cyclodextrin inclusion complexes. Eur J Pharm Biopharm. 2004;51:263–7.
Sajeesh S, Sharma CP. Cyclodextrin–insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery. Int J Pharm. 2006;325:147–54.
Chen X, Chen R, Guo Z, Li C. The preparation and stability of the inclusion complex of astaxanthin with β-CD. Food Chem. 2007;101:1580–4.
Semalty A, Semalty M, Singh D, Rawat MSM. Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery. J Incl Phenom Macrocycl Chem. 2010;67:253–60.
Singh D, Rawat MSM, Semalty A, Semalty M. Emodin–phospholipid complex: a potential of herbal drug in the novel drug delivery system. J Therm Anal Calorim. 2012;108:289–98.
Semalty A, Semalty M, Singh D, Rawat MSM. Phyto-phospholipid complex of catechin in value added herbal drug delivery. J Incl Phenom Macrocycl Chem. 2012;69:253–60.
Semalty A, Semalty M, Rawat MSM, Federico F. Supramolecular phospholipids-polyphenolic interactions: the PHYTOSOME strategy to improve the bioavailability of phytochemicals. Fitoterapia. 2010;81:306–14.
Semalty A, Semalty M, Rawat BS, Singh D, Rawat MSM. Pharmacosomes: the lipid based novel drug delivery system. Expert Opin Drug Deliv. 2009;6(6):599–612.
Singh D, Rawat MSM, Semalty A, Semalty M. Gallic acidphospholipid complex: drug incorporation and physicochemical characterization. Lett Drug Design Disc. 2011;8(3):284–91.
Magnusdottir M, Lofisson T. Cyclodextrins. J Incl Phenom Macroc Chem. 2002;44:213–8.
Rasheed A, Kumar A. Cyclodextrin as drug carrier molecule. Sci Pharm. 2008;76:567–98.
Magnusdottir A, Masson M, Loftsson T. Cyclodextrin in drug delivery. Expert Opin Drug Deliv. 2005;2:335–51.
Irie T, Uekama K. Pharmaceutical application of cyclodextrin. Toxicological issues and safety evaluation. J Pharma Sci. 1997;85:147–62.
Del VE. Cyclodextrins and their uses: a review. Process Biochem. 2004;39:1033–46.
Rinaki E, Valsami G, Macheras P. Quantitative biopharmaceutical classification system: the central role of dose/solubility ratio. Pharma Res. 2003;20:1917–9.
Vekama K. Design and evaluation of cyclodextrin based drug formulation. Chem Pharm Bull. 2004;52:900–15.
Sathigari S, Chadha G, Lee Y-HP, Wright N, Parsons DL, Rangari VK, Fasina O, Babu RB. Physicochemical characterization of efavirenz–cyclodextrin inclusion complexes. AAPS PharmSciTech. 2009. doi:10.1208/s12249-008-9180-3.
Rajendrakumar K, Madhusudan S, Pralhad T. Cyclodextrin complexes of valdecoxib: properties and anti-inflammatory activity in rat. Eur J Pharm Biopharm. 2005;60:39–46.
Zielenkiewicz W, Koźbiał M, Golankiewicz B, Poznański J. Enhancement of aqueous solubility of tricyclic acyclovir derivatives by their complexation with hydroxypropyl-β-cyclodextrin. J Therm Anal Calorim. 2010;101:555–60.
Menezes PP, Serafini MR, Quintans-Júnior LJ, Silva GF, Oliveira JF, Carvalho FMS, Souza JCC, Matos JR, Alves PB, Matos IL, Hădărugă DI, Araújo AAS. Inclusion complex of (−)-linalool and β-cyclodextrin. J Therm Anal Calorim. 2013. doi:10.1007/s10973-013-3367-x.
Ambrus R, Aigner Z, Catenacci L, Bettinetti G, Szabó-Révész P, Sorrenti M. Physico-chemical characterization and dissolution properties of nifluminic acid-cyclodextrin-PVP ternary systems. J Therm Anal Calorim. 2011;104:291–7.
Singh D, Rawat MSM, Semalty A, Semalty M. Chrysophanol–phospholipid complex. J Therm Anal Calorim. 2013;111:2069–77.
Acknowledgements
Authors are thankful to Wadia Institute of Himalayan Geology, Dehradun, Uttarakhand for providing SEM facility. Facilities provided by the UGC-DAE Consortium for Scientific Research, Indore (M.P.) are thankfully acknowledged.
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Semalty, A., Tanwar, Y.S. & Semalty, M. Preparation and characterization of cyclodextrin inclusion complex of naringenin and critical comparison with phospholipid complexation for improving solubility and dissolution. J Therm Anal Calorim 115, 2471–2478 (2014). https://doi.org/10.1007/s10973-013-3463-y
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DOI: https://doi.org/10.1007/s10973-013-3463-y