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.
Similar content being viewed by others
References
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.
Garg A, Garg S, Zaneveld LJD, Singla AK. Review article: chemistry and pharmacology of the citrus bioflavonoid hesperedin. Phytother Res. 2001;15:655–69.
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.
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.
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.
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.
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.
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.
Calomme M, Pieters L, Vlietinck A, Berghe DV. Inhibition of bacterial mutagenesis by Citrus flavonoids. Planta Med. 1996;62:222–6.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Palmieri GF, Bonacucina G, Di Martino P, Martelli S. Gastro-resistant microspheres containing ketoprofene. Journal of Microencapsulation. 2002;19:111–9.
Giunchedi P, Conte U. Spray drying as preparation method of microparticulate drug delivery systems: an overview. STP Pharm Sci. 1990;5:276–90.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-009-9219-0