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β-Cyclodextrin-based inclusion complexes and nanocomposites of rivaroxaban for solubility enhancement

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Abstract

Rivaroxaban (RIV) is an oral anticoagulant used in the prevention of venous thromboembolism in adult patients after total hip replacement or total knee replacement surgery. It is practically insoluble in water and buffer systems (pH 3–9). The present study was aimed to investigate the β-CD-based inclusion complexes and nanocomposites of rivaroxaban (RIV) for solubility and dissolution enhancement. A novel solubility enhancement approach of inclusion complexation of RIV with β-CD using spray drying method combined with high pressure homogenization as a particle engineering method was used. Change in crystallinity of RIV nanocomposites was assessed by DSC and PXRD. The interaction of drug with β-CD was projected through 1H-NMR and FT-IR studies. Saturation solubility and in vitro dissolution study revealed a dramatic increase in solubility and dissolution of RIV, respectively. Thus, spray-dried β-CD-based nanocomposites could be an innovative approach for solubility and dissolution enhancement of RIV.

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References

  1. Duggan ST, Scott LJ, Rivaroxaban GL. A review of its use for the prevention of venous thromboembolism after total hip or knee replacement surgery. Drugs. 2009;69:1829–51.

    Article  CAS  Google Scholar 

  2. Bayer Inc., Canada. Product Monograph PrXARELTO®. 2018. Accessed 24 Feb 2018 (https://www.bayer.ca/omr/online/xarelto-pm-en.pdf).

  3. Roine J, Kaasalainen M, Peurla M, Correia A, Araujo F, Santos HA et al. Controlled dissolution of griseofulvin solid dispersions from electrosprayed enteric polymer micromatrix particles: physicochemical characterization and in vitro evaluation. Mol Pharm. 2015;12:2254–64.

    Article  CAS  Google Scholar 

  4. Seulki L, Sang KK, Dong YL, Kyeongsoon P, Tadiparthi S, Suy C et al. Cationic analog of deoxycholate as an oral delivery carrier for ceftriaxone. J Pharm Sci. 2005;94:2541–8.

    Article  Google Scholar 

  5. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–25.

    Article  CAS  Google Scholar 

  6. Miranda de J, de Miranda JC, Martins TEA, Veiga F, Ferraz HG. Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs. Braz J Pharm Sci. 2011;47:665–81.

    Article  Google Scholar 

  7. Li L, Ma P, Cao Y, Tao L, Tao YJ. Single-dose and multiple-dose pharmacokinetics of zaltoprofen after oral administration in healthy Chinese volunteers. Biomed Res. 2011;25:56–62.

    Article  Google Scholar 

  8. Jansook P, Loftsson T. CDs as solubilizers: effects of excipients and competing drugs. Int J Pharm. 2009;379:32–40.

    Article  CAS  Google Scholar 

  9. Brewster ME, Vandecruys R, Peeters J, Neeskens P, Verreck G, Loftsson T. Comparative interaction of 2-hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin with itraconazole: phase-solubility behaviour and stabilization of supersaturated drug solutions. Eur J Pharm Sci. 2008;34:94–103.

    Article  CAS  Google Scholar 

  10. George SJ, Vasudevan DT. Studies on the preparation, characterization, and solubility of 2-HP-β-cyclodextrin–meclizine HCI inclusion complexes. J Young Pharm. 2012;4:220–7.

    Article  CAS  Google Scholar 

  11. Ma S-X, Chen W, Yang X-D, Zhang N, Wang S-J, Liu L et al. Alpinetin/hydroxypropyl-β-cyclodextrin host–guest system: preparation, characterization, inclusion mode, solubilization and stability. J Pharm Biomed Anal. 2012;67–68:193–200.

    Article  Google Scholar 

  12. Swaminathan S, Pastero L, Serpe L, Trotta F, Vavia P, Aquilano D et al. Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity. Eur J Pharm Biopharm. 2010;74:193–201.

    Article  CAS  Google Scholar 

  13. Wang D, Li H, Gu J, Guo T, Yang S, Gou Z et al. Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions. J Pharm Biomed Anal. 2013;83:141–8.

    Article  CAS  Google Scholar 

  14. Granero GE, Maitre MM, Garnero C. Synthesis, characterization and in vitro release studies of a new acetazolamide-HP-[beta]-CD-TEA inclusion complex. Eur J Med Chem. 2008;43:464–70.

    Article  CAS  Google Scholar 

  15. Canbolat MF, Celebioglu A, Uyar T. Drug delivery system based on cyclodextrin–naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers. Colloids Surf B. 2014;115:15–21.

    Article  CAS  Google Scholar 

  16. Adhage NA, Vavia PR. β-Cyclodextrin inclusion complexation by milling. Pharm Pharmacol Commun. 2000;6:13–7.

    Article  CAS  Google Scholar 

  17. Magnusdottir A, Masson M, Loftsson T. Self-association and cyclodextrin solubilisation of NSAIDs. J Incl Pheno Macro Chem. 2002;44:213–8.

    Article  CAS  Google Scholar 

  18. Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizer. Adv Drug Del Rev. 2007;9:645–66.

    Article  Google Scholar 

  19. Sherje A, Kulkarni V, Murahari M, Nayak U, Bhat P, Suvarna V et al. Inclusion complexation of etodolac with hydroxypropyl-beta-cyclodextrin and auxiliary agents: formulation characterization and molecular modelling studies. Mol Pharm. 2017;14:1231–42.

    Article  CAS  Google Scholar 

  20. Suvarna V, Kajwe A, Murahari M, Pujar GV, Inturi BK, Sherje A. Inclusion complexes of nateglinide with HP-β-CD and L-Arginine for solubility and dissolution enhancement: preparation, characterization, and molecular docking Study. J Pharm Innov. 2017;12:168–81.

    Article  Google Scholar 

  21. Vakani S, Kajwe A, Suvarna V, Sherje AP. Influence of auxiliary agents on solubility and dissolution profile of repaglinide with hydroxypropyl-β-cyclodextrin: Inclusion complex formation and its solid-state characterization. J Incl Pheno Macro Chem. 2015;83:239–50.

    Article  CAS  Google Scholar 

  22. Sherje AP, Londhe V. Ternary inclusion complex of paliperidone with β-cyclodextrin and hydrophilic polymer for solubility and dissolution enhancement. J Pharm Innov. 2015;10:324–34.

    Article  Google Scholar 

  23. Sherje AP, Patel F, Murahari M, Suvarna V, Patel K. Study on effect of L-arginine on solubility and dissolution of Zaltoprofen: preparation and characterization of binary and ternary cyclodextrin inclusion complexes. Chem Phys Lett. 2018;694:120–8.

    Article  CAS  Google Scholar 

  24. Suvarna V, Thorat S, Nayak U, Sherje A, Murahari M. Host-guest interaction study of Efavirenz with hydroxypropyl-β-cyclodextrin and L-arginine by computational simulation studies: preparation and characterization of supramolecular complexes. J Mol Liq. 2018;259:55–64.

    Article  CAS  Google Scholar 

  25. Sangwai M, Vavia P. Amorphous ternary cyclodextrin nanocomposites of telmisartan for oral drug delivery: improved solubility and reduced pharmacokinetic variability. Inter J Pharm. 2016;453:423–32.

    Article  Google Scholar 

  26. Marques HC, Hadgraft J, Kellaway I. Studies of cyclodextrin inclusion complexes. I. The salbutamol-cyclodextrin complex as studied by phase solubility and DSC. Inter J Pharm. 1990;63:259–66.

    Article  Google Scholar 

  27. Baka E, Comer JEA, Takacs-Novak K. Study of equilibrium solubility measurement by saturation shake-flask method using hydrochlorothiazide as model compound. J Pharm Biomed Anal. 2008;46:335–41.

    Article  CAS  Google Scholar 

  28. Food and Drug Administration, FDA/Center for Drug Evaluation and Research, Office of Pharmaceutical Quality/Office of New Drug Products, Division of Biopharmaceutics. Dissolution methods. 2017. https://www.accessdata.fda.gov/scripts/cder/dissolution/dsp_SearchResults.cfm. Accessed 15 Dec 2017.

  29. Ribeiro L, Loftsson T, Ferreira D, Veiga F. Investigation and physicochemical characterization of vinpocetine- sulfobutyl ether beta-cyclodextrin binary and ternary complexes. Chem Pharm Bull. 2003;51:914–22.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are thankful to Symed Laboratories, Hyderabad, India and Gangwal Chemicals, Mumbai, India, respectively for gift sample of Rivaroxaban and β-cyclodextrin, respectively.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry & Quality Assurance, SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, 400 056, India

    Atul P. Sherje & Mrunal Jadhav

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  1. Atul P. Sherje
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  2. Mrunal Jadhav
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Correspondence to Atul P. Sherje.

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Sherje, A.P., Jadhav, M. β-Cyclodextrin-based inclusion complexes and nanocomposites of rivaroxaban for solubility enhancement. J Mater Sci: Mater Med 29, 186 (2018). https://doi.org/10.1007/s10856-018-6194-6

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