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Current Drug Discovery Technologies


ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Ternary Inclusion Complexes of Rifaximin with β-Cyclodextrin and Sodium Deoxycholate for Solubility Enhancement

Author(s): Parminderjit Kaur, Ankit Rampal, Preet M. Singh Bedi and Neena Bedi

Volume 12, Issue 3, 2015

Page: [179 - 189] Pages: 11

DOI: 10.2174/1570163812666150817113230

Price: $65


Rifaximin is a rifamycin derivative, having extremely poor aqueous solubility. The objective of present study was to improve dissolution and solubility of drug using β-cyclodextrin inclusion complexes and also to evaluate the effect of presence of sodium deoxycholate on solubilization efficiency of β-cyclodextrin. The stochiometry of inclusion complexes of binary (drug-cyclodextrin) and ternary system (drug-cyclodextrin-sodium deoxycholate) were determined by phase solubility studies at 25°C. The stability constants (K1:2) calculated from phase solubility analysis were 126M-1 and 267M-1 for binary and ternary systems respectively. The inclusion complexes were prepared by solvent evaporation method with the inclusion efficiency of 43% and 56.9% for binary and ternary systems followed by their characterization using fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry and in-vitro antibacterial activity. The solubility of drug was improved by 4.3 and 11.9 folds in binary and ternary inclusion complexes, respectively. Therefore, it can be concluded that the ternary inclusion complexation having better solubilization efficiency as compared to binary complexation.

Keywords: β-cyclodextrin, FTIR, phase solubility, Rifaximin, ternary inclusion complexes, X-RD, antibacterial.

Graphical Abstract
Mehta P, Morre A, Kulkarni A. Effect of hydrophilic polymers on cefixime complexation with cyclodextrins. Int J Curr Pharm Res 2013; 5: 66-70.
Linderberg M, Dressman J. Classification of orally administered drugs on the WHO model list of essential medicines according to BCS. Eur J Pharm Biopharm 2004; 58: 265-78.
Vemula VR, Lagishetty V, Lingala S. Solubility Enhancement techniques. Int J Pharm Sci Rev Res 2010; 5: 41-51.
Khan AN, Durakshan M. Cyclodextrins: an overview. International Journal of Bioassays 2013; 6: 862-8.
Scarpignato C, Pelosini I. Rifaximin. A poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy 2005; 51: 36-66.
Patil JS, Kadam DS, Kamalapur MV. Inclusion complex system: A novel technique to improve the solubility and bioavailability of poorly soluble drugs: a review. Int J Pharm Sci Rev Res 2010; 2: 25-39.
Brewster M, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev 2007; 59: 645-69.
Mura P, Cirri M, Zerrouki N. Improvement of oxaprozin solubility and permeability by combined use of chitosan, cyclodextrin and bile salts. Eur J Pharm Biopharm 2011; 78: 385-93.
Elizabeth J, Dial J, Herbert L, Darkoh C. Bile salts improve antimicrobial activity of rifaximin. Antimicrob Agents Chemother 2010; 54: 618-9.
Higuchi T, Connors K. A phase solubility techniques. Advanced Analytical Chemical Instrumentation 1965; 4: 117-211.
Crestani JM, Martin ATE, Veiga F, Humberto G. Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs. J Pharm Sci 2011; 47: 665-81.
Bidyut N, Amrutansu P, Annapurna MM. Spectroscopic estimation of rifaximin in pure form and in tablet form. International Journal of Pharmacy and Technology 2010; 2: 1028-38.
Loftsson T, Masson M. Evaluation of cyclodextrin inclusion complexes. Int J Pharm 2005; 302: 456-503.
Haziadbic J, Elizovic A, Muzejin I. Effect of cyclodextrin inclusion complexation on the aqueous solubility of diazepam and nitrazepam: phase solubility analysis and thermodynamic properties. American Journal of Analytical Chemistry 2012; 3: 811-9.
Banchero M, Manna L. Use of lysine to enhance the supercritical complexation of ketoprofen and cyclodextrins. J Supercrit Fluids 2012; 67: 76-83.
Chadha R, Arora P, Gupta S. Complexation of nevirapine with β-cyclodextrin in the absence and presence of tween 80: characterization, thermodynamic parameters and permeability flux. Journal of Thermodynamic and Analytical Colorimetry 2011; 105: 1049-59.
Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: drug solubilization and stabilization. J Pharm Sci 2007; 85: 1017-25.
Hees VT, Piel G, Delattere L. Determination of the free included piroxicam ratio in cyclodextrin complexes: comparison between U.V. spectrophotometry and differential scanning calorimetry. Eur J Pharm Sci 2002; 15: 345-53.
Mukne PA, Nagarsenkar MS. Triamterene-β-cyclodextrin systems: preparation, characterization and in-vivo evaluation. AAPS PharmSciTech 2004; 5: E19.
Sinha VR, Anitha R, Kumria R, Ghosh S. Complexation of celecoxib with β-cyclodextrin: Characterization of interaction in solution and solid state. J Pharm Sci 2005; 94: 645-56.
Bugay DE. Characterization of the solid state: spectroscopic techniques. Adv Drug Deliv Rev 2001; 48: 43-65.
Ribreio L, Loftsson T, Veiga F. Investigation and physicochemical characterization of vinpocetine-sulfobutyl-ether-β-cyclodextrin binary and ternary system. Chem Pharm Bull (Tokyo) 2003; 8: 914-22.
Karanth H, Shenoy VS. Solubility parameters influence on the in-vitro release and antibacterial activity of sparfloxacin. Indian Drugs 2005; 42: 222-7.
Solanki NS, Yaduvanshi KS, Jain V, et al. Synthesis and Antimicrobial Activity of Di (Substituted Phenyl)-2 Pyrazoline Derivatives. Int J Pharm Tech Res 2012; 4: 1465-8.
Chalkley LJ, Koornof HJ. Antibacterial activity of ciprofloxacin against Staphylococcus aureus and E.coli determined by billiary curve method: Antibiotic comparisons and synergistic infections. Antimicrob Agents Chemother 1985; 28: 331-42.
Sathigiri S, Chadha G, Lee P, Babu J. Physicochemical characterization of efavirenz-cyclodextrin inclusion complexes. AAPS PharmSciTech 2009; 10: 81-7.
Ajmera A, Deshpande S, Kharadi S. Dissolution Rate Enhancement of Atorvastation, Fenobirate and Ezetimibe by inclusion complex with β-Cyclodextrin. Asian Journal of Pharmaceutical and Clinical Research 2012; 5: 73-6.
Priya SA, Siyakamavlli J, Stalin T. Improvement on dissolution rate of rifabutin with β-cyclodextrin. Int J Biol Macromol 2013; 60: 462-72.
Kulkarni S, Dalal S. Solid dispersion of rifaximin European Patent 000694 2010.
Ghagare MG, Kumar S, Ramachandaran D. Rifaximin Complexes United States Patent 002854, 2009.
Karanje V, Bhavsar VY. Formulation and development of micro particulate drug delivery system of solubilized rifaximin. AAPS PharmSciTech 2013; 14: 639-50.
Patel A, Vavia P. Preparation and evaluation of taste masked famotidine formulation using drug/cyclodextrin/polymer ternary complexation approach. AAPS PharmSciTech 2008; 9: 544-8.
Lamba SS, Chowdhary KR. A factorial study on the formulation development of the efavirenz by employing β-cyclodextrin and poloxamer-188. Int J Pharm Sci Res 2012; 3: 210-2.

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