Skip to main content

Advertisement

SpringerLink
Log in

Fluidized Bed Hot-Melt Granulation as a Tool to Improve Curcuminoid Solubility

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Curcumin is the main bioactive component of Curcuma longa L. and has recently aroused growing interest from the scientific community. Unfortunately, the medicinal properties attributed to curcuminoids are impaired by their low oral bioavailability or low solubility in aqueous solutions. Many strategies have been studied to improve curcumin solubility; however, the preparation of granules using hydrophilic materials has never been attempted. The aim of this work was to develop curcumin granules by fluidized bed hot-melt granulation using the hydrophilic carrier Gelucire® 50:13. A two-level factorial design was used to verify the influence of Gelucire® 50:13 and lactose contents found in the granules on their size, morphology, bulk and tapped densities, flow, moisture content, and water activity. The granules obtained were also evaluated by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and infrared spectrometry. The curcumin solubility and dissolution rates in water were determined by liquid chromatography. The best formulation provides an increase of curcumin solubility of 4642-fold and 3.8-fold compared to the physical mixture. The dissolution tests showed a maximum drug release from granules after 45 min of 70% at pH 1.2 and 80% at pH 5.8 and 7.4, while for non-granulated curcumin, the release was below 20% in all pH. The solid-state characterization and solubility measurement showed good stability of granules over 9 months. The results attest that the fluidized bed hot-melt granulation with hydrophilic binders is an attractive and promising alternative to obtain solid forms of curcumin with enhanced bioavailability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895–900.

    CAS  PubMed  Google Scholar 

  2. Tilak JC, MB HM, Devasagayam TPA. Antioxidant availability of turmeric in relation to its medicinal and culinary uses. Phytother Res. 2004;18(10):798–804. https://doi.org/10.1002/ptr.1553.

    Article  PubMed  Google Scholar 

  3. Srimal RC. Turmeric: a brief review of medicinal properties. Fitoterapia. 1997;68:483–93.

    Google Scholar 

  4. Jayaprakasha GK, Jaganmoham R, Sakariah KK. Chemistry and biological activities of C. longa. Trends Food Sci Technol. 2005;16:533–48.

    Article  CAS  Google Scholar 

  5. Freitas LA, Teixeira CCC, Zamarioli CM. Tumeric: therapeutical actions and toxicity. In Tumeric: nutritional properties, uses and potential benefits. New York: Nova Science Publisher, Inc.; 2015. p. 1–50.

  6. Teixeira CC, Mendonca LM, Bergamaschi MM, Queiroz RH, Souza GE, Antunes LM, et al. Microparticles containing curcumin solid dispersion: stability, bioavailability and anti-inflammatory activity. AAPS PharmSciTech. 2016; https://doi.org/10.1208/s12249-015-0337-6.

  7. Tonnesen HH. Solubility, chemical and photochemical stability of curcumin in surfactant solutions—studies of curcumin and curcuminolds, XXVIII. Die Pharmazie. 2002;57(12):820–4.

    CAS  PubMed  Google Scholar 

  8. Bambirra MLA, Junqueira RG, Gloria MB. Influence of post harvest processing conditions on yield and quality of ground turmeric (Curcuma Longa L.). Braz Arch Biol Technol. 2002;45(4):423–9.

    Article  Google Scholar 

  9. Tonnesen HH. Solubility and stability of curcumin in solutions containing alginate and other viscosity modifying macromolecules. Studies of curcumin and curcuminoids. XXX. Die Pharmazie. 2006;61(8):696–700.

    PubMed  Google Scholar 

  10. Paradkar A, Ambike AA, Jadhav BK, Mahadik KR. Characterization of curcumin-PVP solid dispersion obtained by spray drying. Int J Pharm. 2004;271(1–2):281–6.

    Article  CAS  PubMed  Google Scholar 

  11. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50(1):47–60.

    Article  CAS  PubMed  Google Scholar 

  12. Araújo RR, Teixeira CCC, Freitas LAP. The preparation of ternary solid dispersions of an herbal drug via spray drying of liquid feed. Dry Technol. 2010;28(3):412–21. https://doi.org/10.1080/07373931003648540.

    Article  Google Scholar 

  13. Naksuriya O, Okonogi S, Schiffelers RM, Hennink WE. Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials. 2014;35(10):3365–83. https://doi.org/10.1016/j.biomaterials.2013.12.090.

    Article  CAS  PubMed  Google Scholar 

  14. Okonogi S, Puttipipatkhachorn S. Dissolution improvement of high drug-loaded solid dispersion. AAPS PharmSciTech. 2006;7(2)

  15. Yuksel N, Karatas A, Ozkan Y, Savaser A, Ozkan SA, Baykara T. Enhanced bioavailability of piroxicam using Gelucire 44/14 and labrasol: in vitro and in vivo evaluation. Europe J Pharmaceut Biopharmaceut : Off J Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV. 2003;56(3):453–9.

    Article  CAS  Google Scholar 

  16. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12(23/24):1068–75.

    Article  CAS  PubMed  Google Scholar 

  17. Martins RM, Machado MO, Pereira SV, Nosari ABFL, Tacon LA, Freitas LAP. Engineering active pharmaceutical ingredients by spray drying: effects on physical properties and in vitro dissolution. Dry Technol. 2012;30:905–13.

    Article  CAS  Google Scholar 

  18. Corrigan OI, Holohan EM, Reilly MR. Physicochemical properties of indomethacin and related compounds co-spray dried with polyvinylpyrrolidone. Drug Dev Ind Pharm. 1985;11:677–95.

    Article  CAS  Google Scholar 

  19. Law SL, Lo WY, Lin FM, H CC. Dissolution and absorption of nifedipine in polyethylene glycol solid dispersion containing phosphatidylcholine. Int J Pharmarceut. 1982;84:161–6.

    Article  Google Scholar 

  20. Mura P, Manderiolo A, Bramanti G, Ceccarelli L. Properties of solid dispersions of naproxen in various polyethyleneglycols. Drug Dev Ind Pharm. 1986;22:909–16.

    Article  Google Scholar 

  21. Ozeki T, Yuasa H, Kanaya Y, Oishi K. Application of the solid dispersion method to the controlled release of medicine. VIII. Medicine release and viscosity of the hydrogel of a water-soluble polymer in a three-component solid dispersion system. Chem Pharmaceut Bull. 1995;43:660–5.

    Article  CAS  Google Scholar 

  22. Craig DQ. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2002;231(2):131–44.

    Article  CAS  PubMed  Google Scholar 

  23. Ford JL. The current status of solid dispersions. Pharm Acta Helv. 1986;61(3):69–88.

    CAS  PubMed  Google Scholar 

  24. Achanta AS, Adusumilli PS, James KW, Rhodes CT. Hot-melt coating: water sorption behavior of excipient films. Drug Dev Ind Pharm. 2001;27(3):241–50.

    Article  CAS  PubMed  Google Scholar 

  25. Guimaraes TF, Comelli ACC, Tacon LA, Cunha TA, Marreto RN, Freitas LAP. Fluidized bed hot melt granulation with hydrophilic materials improves enalapril maleate stability. AAPS PharmSciTech. 2016;18(4):1302–10. https://doi.org/10.1208/s12249-016-0593-0.

    Article  PubMed  Google Scholar 

  26. Haramiishi Y, Kitazawa Y, Sakai M, Kataoka K. Study on fluidized melt-granulation. I. Examination of the factors on the glanulation. Yakugaku Zasshi: J Pharmaceut Soc Jap. 1991;111:515–23.

    Article  CAS  Google Scholar 

  27. Kidokoro M, Haramiishi Y, Sagasaki S, Shimizu T, Yamamoto Y. Application of fluidized hot-melt granulation (FHMG) for the preparation of granules for tableting; properties of granules and tablets prepared by FHMG. Drug Dev Ind Pharm. 2002;28(1):67–76. https://doi.org/10.1081/DDC-120001487.

    Article  CAS  PubMed  Google Scholar 

  28. Villanova JCO, Ayres E, Orefice RL. Design of prolonged release tablets using new solid acrylic excipients for direct compression. Eur J Pharm Biopharm. 2011;79:664–73.

    Article  CAS  PubMed  Google Scholar 

  29. Nist/Sematech. e-Handbook of statistical methods. 2012 [updated 2012, April]; Available from: http://www.itl.nist.gov/div898/handbook/.

  30. Harmonisation. ICo. Guidance for industry Q1A(R2) stability testing of new drug substances and products. In: Dept. of Health and Human Services, editor. Rockville, MD : U.S. : Food and Drug Administration, Center for Drug Evaluation and Research; 2003.

  31. American Pharmacopeia. USP XXX: United States pharmacopeial convention, in: United States Pharmacopeial convention, USP: Rockville, MD 2008.

  32. Damian F, Blaton N, Naesens L, Balzarini J, Kinget R, Augustijns P, et al. Physicochemical characterization of solid dispersions of the antiviral agent UC-781 with polyethylene glycol 6000 and Gelucire 44/14. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2000;10(4):311–22.

    Article  CAS  Google Scholar 

  33. Haque MK, Roos YH. Crystallization and X-ray diffraction of spray-dried and freeze-dried amorphous lactose. Carbohydr Res. 2005;340(2):293–301. https://doi.org/10.1016/j.carres.2004.11.026.

    Article  CAS  PubMed  Google Scholar 

  34. Geldart D, Abdullah EC, Hassanpour A, Nwoke LC, Wouters I. Characterization of powder flowability using measurement of angle of repose. China Particuology. 2006;4(3–4):104–7.

    Article  Google Scholar 

  35. Serajuddin AT. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999;88(10):1058–66.

    Article  CAS  PubMed  Google Scholar 

  36. Wang W, Zhou WB. Characterization of spray-dried soy sauce powders using maltodextrins as carrier. J Food Eng. 2012;109:399–405.

    Article  CAS  Google Scholar 

  37. Gupta MK, Tseng YC, Goldman D, Bogner RH. Hydrogen bonding with adsorbent during storage governs drug dissolution from solid-dispersion granules. Pharm Res. 2002;19(11):1663–72.

    Article  CAS  PubMed  Google Scholar 

  38. Chauhan B, Shimpi S, Paradkar A. Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2005;26(2):219–30. https://doi.org/10.1016/j.ejps.2005.06.005.

    Article  CAS  Google Scholar 

  39. Kakkar V, Kaur IP. Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium induced behavioural, biochemical and histopathological alterations in mice brain. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2011;49(11):2906–13. https://doi.org/10.1016/j.fct.2011.08.006.

    Article  CAS  Google Scholar 

Download references

Funding

The financial support from FAPESP (2013/23327-5; 2015/25128-5) and CNPq (PQ-2) is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Instituto Nacional de Ciência e Tecnologia-INCT-Nanotecnologia Farmacêutica, Universidade de São Paulo, Via do Café s/n, Campus USP, Ribeirão Preto, SP, 14040-903, Brazil

    Cristiane C. C. Teixeira, Elias de Paiva Junior & Luis Alexandre Pedro de Freitas

Authors
  1. Cristiane C. C. Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elias de Paiva Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luis Alexandre Pedro de Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luis Alexandre Pedro de Freitas.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teixeira, C.C.C., de Paiva Junior, E. & de Freitas, L.A.P. Fluidized Bed Hot-Melt Granulation as a Tool to Improve Curcuminoid Solubility. AAPS PharmSciTech 19, 1061–1071 (2018). https://doi.org/10.1208/s12249-017-0909-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-017-0909-8

KEY WORDS

Search

Navigation