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Hesperidin Gastroresistant Microparticles by Spray-Drying: Preparation, Characterization, and Dissolution Profiles

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Abstract

Gastroresistant microparticles for oral administration of hesperidin (Hd) were produced by spray-drying using cellulose acetate phthalate (CAP) as enteric polymer in different polymer/Hd weight ratio (1:1, 3:1, and 5:1), and a series of enhancers of the dissolution rate, such as sodium carboxymethylcellulose crosslinked (CMC), sodium dodecylbenzene sulfonate (SDBS), or Tween85. The raw materials and the microparticles were investigated by differential-scanning calorimetry, X-ray diffraction, infrared spectroscopy and imaged using scanning electron and fluorescence microscopy. In vitro dissolution tests were conducted using a pH-change method to investigate the influence of formulative parameters on the dissolution/release properties of the drug. CAP/Hd microparticles showed a good gastro-resistance but incomplete drug dissolution in the simulated intestinal fluid (SIF). The presence of the enhancers in the formulation produced well-formed microparticles with different size and morphology, containing the drug well coated by the polymer. All the enhancers were able to increase the dissolution rate of Hd in the simulated intestinal environment without altering CAP ability to protect Hd in the acidic fluid. The spray-drying technique and process conditions selected were effective in microencapsulating and stabilizing the flavonoid giving satisfactory encapsulation efficiency, product yield, and microparticles morphology, and a complete drug release in the intestine.

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References

  1. Barthe GA, Jourdan PS, McIntosh CA, Mansell RL. Radioimmunoassay for the quantitative determination of hesperedin and analysis of its distribution in Citrus sinensis. Phytochemistry 1988;27:249–54.

    Article  CAS  Google Scholar 

  2. Garg A, Garg S, Zaneveld LJD, Singla AK. Review article: chemistry and pharmacology of the citrus bioflavonoid hesperedin. Phytother Res. 2001;15:655–69.

    Article  PubMed  CAS  Google Scholar 

  3. Bok SH, Lee SH, Park YB, Bae KH, Son KH, Jeong TS, et al. Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA: cholesterol transferases are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J Nutr. 1999;129:1182–5.

    PubMed  CAS  Google Scholar 

  4. Hirata A, Murakami Y, Shoji M, Kadoma Y, Fujisawa S. Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression. Anticancer Res. 2005;25:3367–74.

    PubMed  CAS  Google Scholar 

  5. Horcajada MN, Coxam V. Hesperidin, a citrus flavanone, improves bone acquisition and prevents skeletal impairment in rats in nutritional aspects of osteoporosis. 2nd ed. New York: Elsevier; 2004. p. 103–20.

    Google Scholar 

  6. Yang M, Tanaka T, Hirose Y, Deguchi T, Mori H, Kawada Y. Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl)nitrosamine induced urinary bladder carcinogenesis in male ICR mice. Int J Can. 1997;73:719–24.

    Article  CAS  Google Scholar 

  7. Franke AA, Cooney RV, Custer LJ, Mordan LJ, Tanaka Y. Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents. Adv Exp Med Biol. 1998;439:237–28.

    PubMed  CAS  Google Scholar 

  8. Choi JS, Park KY, Moon SH, Rhee SH, Young HS. Antimutagenic effects of plant flavonoids in the Salmonella assay system. Arch Pharm Res. 1994;17:71–5.

    Article  PubMed  CAS  Google Scholar 

  9. Calomme M, Pieters L, Vlietinck A, Berghe DV. Inhibition of bacterial mutagenesis by Citrus flavonoids. Planta Med. 1996;62:222–6.

    Article  PubMed  CAS  Google Scholar 

  10. Tanaka T, Makita H, Kawabata K, Mori H, Kakumoto M. Modulation of N-methyl-N-amylnitrosamine induced tumorigenesis by dietary feeding of diosmin and hesperidin, alone and in combination. Carcinogenesis 1997;18:957–65.

    Article  PubMed  CAS  Google Scholar 

  11. Beninati S. Transglutaminase activity and protein polyamine binding capacity in animal and plants cells. In: Pandalai G, editor. Recent developments in phytochemistry. vol 1. Kerala: Research Signpost; 1997. p. 243–53.

    Google Scholar 

  12. Lentini A, Forni C, Provengano B, Beninati S. Enhancement of transglutaminase activity and polyamine depletion in B16-F10 melanoma cells by flavonoids naringenin and hesperitin correlate to reduction of the in vivo metastatic potential. Amino Acids. 2007;32:95–100.

    Article  PubMed  CAS  Google Scholar 

  13. Thacher SM, Rice RH. Keratinocyte-specific transglutaminase of cultured human epidermal cells: relation to cross-linked envelope formation and terminal differentiation. Cell 1985;40:685–95.

    Article  PubMed  CAS  Google Scholar 

  14. Benedetti L, Grignani F, Scicchitano BM, Jetten AM, Diverio D, Lococo F, et al. Retinoid-induced differentiation of acute promyelocytic leukemia involves PML-RAalpha-mediated increase of type II transglutaminase. Blood 1996;87:1939–50.

    PubMed  CAS  Google Scholar 

  15. Arani I, Adler-Storthz K, Trying SK, Brysk H, Brysk MM. Differentiation markers in oral carcinoma cell lines and tumors. Anticancer Res. 1997;17:4607–10.

    Google Scholar 

  16. Kanaze FI, Kokkolou E, Niopas I, Georgarakis M, Stergiou A, Bikiaris D. Thermal analysis study of flavonoid solid dispersion having enhanced solubility. J Therm Anal Calorim. 2006;83:283–90.

    Article  CAS  Google Scholar 

  17. Lauro MR, Maggi L, Conte U, De Simone F, Aquino RP. Quercetin gastro-resistant microparticles obtained by spray-drying technique. J Drug Del Sci Tech. 2005;15:363–9.

    CAS  Google Scholar 

  18. Lauro MR, De Simone F, Sansone F, Iannelli P, Aquino RP. Preparation and release chacteristics of naringin and naringenin gastro-resistant microparticles by spray-drying. J Drug Del Sci Tech. 2007;17:119–24.

    CAS  Google Scholar 

  19. Palmieri GF, Bonacucina G, Di Martino P, Martelli S. Gastro-resistant microspheres containing ketoprofene. Journal of Microencapsulation. 2002;19:111–9.

    Article  PubMed  CAS  Google Scholar 

  20. Giunchedi P, Conte U. Spray drying as preparation method of microparticulate drug delivery systems: an overview. STP Pharm Sci. 1990;5:276–90.

    Google Scholar 

  21. Gaylord N, Schor LM. Controlled release solid drug dosage forms based on mixture of water soluble non-ionic cellulose ethers and anionic surfactants. US Patent 1989;4849229.

  22. Tommasini S, Calabrò ML, Raneri D, Ficarra P, Ficarra R. Combined effect of pH and polysorbates with cyclodextrins on solubilization of naringenin. J Pharm Biomed Anal. 2004;36:327–33.

    Article  PubMed  CAS  Google Scholar 

  23. Sangalli ME, Giunchedi P, Colombo P, Gazzaniga A, La Manna A. Cross-linked sodium carboxymethylcellulose as a carrier for dissolution rate improvement of drugs. Boll Chim Farm. 1989;128:242–7.

    PubMed  CAS  Google Scholar 

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Correspondence to Maria Rosaria Lauro.

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Sansone, F., Rossi, A., Del Gaudio, P. et al. Hesperidin Gastroresistant Microparticles by Spray-Drying: Preparation, Characterization, and Dissolution Profiles. AAPS PharmSciTech 10, 391–401 (2009). https://doi.org/10.1208/s12249-009-9219-0

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