AAPS PharmSciTech

, Volume 13, Issue 1, pp 159–166 | Cite as

Improved Bioavailability of Poorly Water-Soluble Drug Curcumin in Cellulose Acetate Solid Dispersion

  • Shuxin Wan
  • Yingqian Sun
  • Xiuxiang Qi
  • Fengping Tan
Research Article

Abstract

Curcumin (Cur), one of the most widely used natural active constituents with a great variety of beneficial biological and pharmacological activities, is a practically water-insoluble substance with a short biologic half-life. The aim of this study was to develop a sustained-release solid dispersion by employing water-insoluble carrier cellulose acetate for solubility enhancement, release control, and oral bioavailability improvement of Cur. Solid dispersions were characterized by solubility, in vitro drug release, Fourier transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry studies. The in vivo performance was assessed by a pharmacokinetic study. Solid-state characterization techniques revealed the amorphous nature of Cur in solid dispersions. Solubility/dissolution of Cur was enhanced in the formulations in comparison with pure drug. Sustained-release profiles of Cur from the solid dispersions were ideally controlled in vitro up to 12 h. The optimized formulation provided an improved pharmacokinetic parameter (Cmax = 187.03 ng/ml, tmax = 1.95 h) in rats as compared with pure drug (Cmax = 87.06 ng/ml, tmax = 0.66 h). The information from this study suggests that the developed solid dispersions successfully enhanced the solubility and sustained release of poorly water-soluble drug Cur, thus improving its oral bioavailability effectively.

Key words

bioavailability cellulose acetate curcumin solid dispersion sustained release 

References

  1. 1.
    Visser MR, Baert L, Klooster GV, Schueller L, Geldof M, Vanwelkenhuysen I, Kock HD, Meyer SD, Frijlink HW, Rosier J, Hinrichs WLJ. Inulin solid dispersion technology to improve the absorption of the BCS class IV drug TMC240. Eur J Pharm Biopharm. 2010;74:233–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50:47–60.PubMedCrossRefGoogle Scholar
  3. 3.
    Huang JJ, Wigent RJ, Bentzley CM, Schwartz JB. Nifedipine solid dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend for controlled drug delivery: effect of drug loading on release kinetics. Int J Pharm. 2006;319:44–54.PubMedCrossRefGoogle Scholar
  4. 4.
    Tanaka N, Imai K, Okimoto K, Ueda S, Tokunaga Y, Ohike A, Ibuki R, Higaki K, Kimura T. Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine. J Control Release. 2005;108:386–95.PubMedCrossRefGoogle Scholar
  5. 5.
    Yang MS, Cui FD, You BG, Wang L, Yue P, Kawashima Y. A novel pH-dependent gradient-release delivery system for nitrendipine II. Investigations of the factors affecting the release behaviors of the system. Int J Pharm. 2004;286:99–109.PubMedCrossRefGoogle Scholar
  6. 6.
    Cui J, Yu B, Zhao Y, Zhu WW, Li HL, Lou HX, Zhai GX. Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems. Int J Pharm. 2009;371:148–55.PubMedCrossRefGoogle Scholar
  7. 7.
    Shaikh J, Ankola DD, Beniwal V, Singh D, Kumar MNVR. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci. 2009;37:223–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Ozeki T, Yuasa H, Kanaya Y. Application of the solid dispersion method to the controlled release of medicine: IX. Difference in the release of flurbiprofen from solid dispersions with poly(ethylene oxide) and hydroxypropylcellulose and the interaction between medicine and polymers. Int J Pharm. 1997;155:209–17.CrossRefGoogle Scholar
  9. 9.
    Hernandez JI, Ghaly ES, Malave A, Marti A. Controlled-release matrix of acetaminophen–ethylcellulose solid dispersion. Drug Dev Ind Pharm. 1994;20(7):1253–65.CrossRefGoogle Scholar
  10. 10.
    Shaikh NA, Abidi SE, Block LH. Evaluation of ethylcellulose as a matrix for prolonged release formulations. II. Sparingly water-soluble drugs: ibuprofen and indomethacin. Drug Dev Ind Pharm. 1987;13(14):2495–518.CrossRefGoogle Scholar
  11. 11.
    Iqbal Z, Babar A, Muhammad A. Controlled-release naproxen using micronized ethyl cellulose by wet-granulation and solid dispersion method. Drug Dev Ind Pharm. 2002;28(2):129–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Zhou HY, Chen XG, Liu CS, Meng XH, Liu CG, Yu LJ. Release characteristics of three model drugs from chitosan/cellulose acetate multimicrospheres. Biochem Eng J. 2006;31:228–33.CrossRefGoogle Scholar
  13. 13.
    Lu B. New techniques and new dosage forms of drugs. 2nd ed. Beijing: People’s Medical Publishing House; 2005. p. 406.Google Scholar
  14. 14.
    Lindstedt B, Ragnarsson G, Hjartstam J. Osmotic pumping as a release mechanism for membrane-coated drug formulations. Int J Pharm. 1989;56:261–8.CrossRefGoogle Scholar
  15. 15.
    Jiang TM, Tan FP, Du JL, Ding FX. Preparation and in vitro release of glipizide loaded controlled release micropheres. J Tsinghua Univ (Sci & Tech). 2004;44(6):732–5.Google Scholar
  16. 16.
    Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–18.PubMedCrossRefGoogle Scholar
  17. 17.
    Tiyaboonchai W, Tungpradit W, Plianbangchang P. Formulation and characterization of curcuminoids loaded solid lipid nanoparticles. Int J Pharm. 2007;337:299–306.PubMedCrossRefGoogle Scholar
  18. 18.
    Yallapu MM, Jaggi M, Chauhan SC. β-cyclodextrin–curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colliod Surf B. 2010;79:113–25.CrossRefGoogle Scholar
  19. 19.
    Liu LX, Wang XC. Improved dissolution of oleanolic acid with ternary solid dispersions. AAPS Pharm Sci Tech. 2007;8(4):E1–5.CrossRefGoogle Scholar
  20. 20.
    Liu CX, Bai RB. Preparation of chitosan/cellulose acetate blend hollow fibers for adsorptive performance. J Membr Sci. 2005;267:68–77.CrossRefGoogle Scholar
  21. 21.
    Juppo AM, Boissier C, Khoo C. Evaluation of solid dispersion particles prepared with SEDS. Int J Pharm. 2003;250:385–401.PubMedCrossRefGoogle Scholar
  22. 22.
    Sinha S, Ali M, Baboota S, Ahuja A, Kumar A, Ail J. Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS Pharm Sci Tech. 2011;11(2):518–27.CrossRefGoogle Scholar
  23. 23.
    Ahuja N, Katare OP, Singh B. Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers. Eur J Pharm Biopharm. 2007;65:26–38.PubMedCrossRefGoogle Scholar
  24. 24.
    Modi A, Tayade P. Enhancement of dissolution profiles by solid dispersion (kneading) technique. AAPS Pharm Sci Tech. 2006;7(3):E1–6.CrossRefGoogle Scholar
  25. 25.
    Cui F, Yang M, Jiang Y, Cun D, Lin W, Fan Y, Kawashima Y. Design of sustained-release nitrendipine microspheres having solid dispersion structure by quasi-emulsion solvent diffusion method. J Control Release. 2003;91:357–84.CrossRefGoogle Scholar
  26. 26.
    Tanaka N, Imai K, Okimoto K, Ueda S, Tokunaga Y, Ibuki R, Higaki K, Kimura T. Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipin (II): in vivo evaluation. J Control Release. 2006;112:51–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Rao BS, Seshasayana A, Saradhi SVP, Kumar NR, Narayan CPS, Murthy KVR. Correlation of ‘in vitro’ release and ‘in vivo’ absorption characteristics of rifampicin from ethylcellulose coated nonpareil beads. Int J Pharm. 2001;230:1–9.CrossRefGoogle Scholar
  28. 28.
    Takka S, Sakr A, Goldberg A. Development and validation of an in vitro–in vivo correlation for buspirone hydrochloride extended release tablets. J Control Release. 2003;88:147–57.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Shuxin Wan
    • 1
  • Yingqian Sun
    • 1
  • Xiuxiang Qi
    • 1
  • Fengping Tan
    • 1
  1. 1.Tianjin Key Laboratory of Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and TechnologyTianjin UniversityTianjinPeople’s Republic of China

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