Fluidized Bed Hot-Melt Granulation as a Tool to Improve Curcuminoid Solubility
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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.
KEY WORDScurcumin hot-melt granulation solid state stability dissolution rate
- 3.Srimal RC. Turmeric: a brief review of medicinal properties. Fitoterapia. 1997;68:483–93.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.Google Scholar
- 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.
- 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.CrossRefPubMedGoogle Scholar
- 14.Okonogi S, Puttipipatkhachorn S. Dissolution improvement of high drug-loaded solid dispersion. AAPS PharmSciTech. 2006;7(2)Google Scholar
- 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.Google Scholar
- 31.American Pharmacopeia. USP XXX: United States pharmacopeial convention, in: United States Pharmacopeial convention, USP: Rockville, MD 2008.Google Scholar
- 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.CrossRefGoogle 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. CrossRefGoogle 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. CrossRefGoogle Scholar