Abstract
The effect of cycloamylose on the aqueous solubility of flurbiprofen was investigated. To improve the solubility and bioavailability of flurbiprofen (poor water solubility), a solid dispersion was spray dried with a solution of flurbiprofen and cycloamylose at a weight ratio of 1:1. The physicochemical properties of solid dispersions were investigated using SEM, DSC, and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with a commercial product. Cycloamylose increased solubility of flurbiprofen approximately 12-fold and dissolution of it by 2-fold. Flurbiprofen was present in an unchanged crystalline state, and cycloamylose was a solubilizing agent for flurbiprofen in this solid dispersion. Furthermore, the dispersion gave higher AUC and Cmax values compared with the commercial product, indicating that it improved the oral bioavailability of flurbiprofen in rats. Thus, the solid dispersion may be useful to deliver flurbiprofen with enhanced bioavailability without changes in crystalline structure.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anderson, B. D. and Conradi, R. A., Predictive Relationships in the water solubility of salts of a nonsteroidal anti-inflammatory drug. J. Pharm. Sci., 74, 815–820 (1985).
Choi, H. G., Oh, Y. K., and Kim, C. K., In-situ gelling and mucoadhesive liquid suppository containing acetaminophen: enhanced bioavailability. Int. J. Pharm., 165, 23–32 (1998).
Choi, H. G., Lee, B. J., Yong, C. S., Rhee, J. D., Han, J. H., Lee, M. K., Park, K. M., and Kim, C. K., Terfenadine-β-cyclodextrin inclusion complex with the anti-histaminic activity enhancement. Drug Dev. Ind. Pharm., 27, 857–862 (2001).
Davies, N. M., Clinical pharmacokinetics of flurbiprofen and its enantiomers. Clin. Pharmacokinet., 28, 100–114 (1995).
Del Valle, E. M. M., Cyclodextrins and their uses: a review. Process Biochem., 39, 1033–1046 (2004).
Doherty, C. and York, P., Mechanisms of dissolution of furosemide: PVP solid dispersions. Int. J. Pharm., 34, 197–205 (1987).
Gessler, K, Usón, I., Takaha, T., Krauss, N., Smith, S. M., Okada, S., Sheldrick, G. M., and Saenger, W., V-Amylose at atomic resolution: X-ray structure of a cycloamylose with 26 glucose residues (cyclomaltohexaicosaose). Proc. Natl. Acad. Sci. U. S. A., 96, 4246–4251 (1999).
Gibaldi, M. and Perrier, D., Pharmacokinetics, 2nd ed. Marcel-Dekker, New York, (1982).
Gupta, G. D., Jain, S., and Jain, N. K., Formulation of an aqueous injection of flurbiprofen. Pharmazie, 52, 709–712 (1997).
Habib, M. J., Phan, M. T., and Owusu-Ababio, G., Dissolution profiles of flurbiprofen in phospholipid solid dispersions. Drug Dev. Ind. Pharm., 24, 1077–1082 (1998).
Higuchi, T. and Connors, K. A., Phase-solubility Techniques. Adv. Anal. Chem. Instrument., 117–212 (1965).
Kim, C. K. and Yoon, Y. S., Preparation and evaluation of flurbiprofen dry elixir as a novel dosage form using a spray drying technique. Int. J. Pharm., 120, 21–31 (1995).
Kitamura, S., Nakatani, K., Takaha, T., and Okada, S., Complex formation of large-ring cyclodextrins with iodine in aqueous solution as revealed by isothermal titration calorimetry. Macromol. Rapid Commun., 20, 612–615 (1999).
Lee, S. W., Kim, M. H., and Kim, C. K., Encapsulation of ethanol by spray drying technique: effects of citric acid. Int. J. Pharm., 187, 193–198 (1999).
Li, D. X., Oh, Y. K., Lim, S. J., Kim, J. O., Yang, H. J., Sung, J. H., Yong, C. S., and Choi, H. G., Novel gelatin microcapsule with bioavailability enhancement of ibuprofen using spray drying technique. Int. J. Pharm., 355, 277–284 (2008).
Li, D. X., Han, M. J., Prabagar, B., Yan, Y. D., Oh, D. H., Joe, J. H., Seo, Y., Kim, J. O., Park, S. M., Yong, C. S., and Choi, H. G., Enhanced oral bioavailability of flurbiprofen by combined use of micelle solution and inclusion compound. Arch. Pharm. Res., 33, 95–101 (2010).
Machida, S., Ogawa, S., Xiaohua, S., Takaha, T., Fujii, K., and Hayashi, K., Cycloamylose as an efficient artificial chaperone for protein refolding. FEBS Lett., 486, 131–135 (2000).
Newa, M., Bhandari, K. H., Li, D. X., Kim, J. O., Yoo, D. S., Kim, J. A., Yoo, B. K., Woo, J. S., Lyoo, W. S., Yong, C. S., and Choi, H. G., Preparation and evaluation of immediate release ibuprofen solid dispersions using polyethylene glycol 4000. Biol. Pharm. Bull., 31, 939–945 (2008).
Oh, D. H., Park, Y. J., Yang, H. J., Kim, Y. I., Kang, J. H., Hwang, D. H., Yong, C. S., and Choi, H. G., Physicochemical characterization and in vivo evaluation of flurbiprofenloaded solid dispersion without crystalline change. Drug Deliv., 18, 46–53 (2011).
Park, K.-M., Gao, Z.-G., and Kim, C.-K., Assay of flurbiprofen in rat plasma using HPLC with fluorescence detection. J. Liq. Chrom. Relat. Tech., 20, 1849–1855 (1997).
Park, K.-M., Lee, M.-K., Hwang, K.-J., and Kim, C.-K., Phospholipid-based microemulsions of flurbiprofen by the spontaneous emulsification process. Int. J. Pharm., 183, 145–154 (1999).
Prabagar, B., Yoo, B. K., Woo, J. S., Kim, J. A., Rhee, J. D., Piao, M. G., Yong, C. S., and Choi, H. G., Enhanced bioavailability of poorly water-soluble clotrimazole by inclusion with β-cyclodextrin, Arch. Pharm. Res., 30, 249–254 (2007).
Shimada, J., Handa, S., Kaneko, H., and Takada, T., Conformation of novel cycloamylose: Topological aspects and simulations. Macromolecules, 29, 6408–6421 (1996).
Society of Toxicology, Guiding Principles in the Use of Animals in Toxicology, (2008): www.toxicology.org/AI/FA/guidingprinciples.pdf.
Szente, L. and Szejtli, J., Cyclodextrins as food ingredients. Trends Food Sci. Technol., 15, 137–142 (2004).
Takaha, T. and Smith, S. M., The functions of 4-α-glucanotransferase and their use for the production of cyclic glucans. Biotechnol. Genet. Eng. Rev., 16, 257–280 (1999).
Tokumura, T., Muraoka, A., and Machida, Y., Improvement of oral bioavailability of flurbiprofen from flurbiprofen/beta-cyclodextrin inclusion complex by action of cinnarizine. Eur. J. Pharm. Biopharm., 73, 202–204 (2009).
Tomono, K., Mugishima, A., Suzuki, T., Goto, H., Ueda, H., Nagai, T., and Watanabe, J., Interaction between cycloamylose and various drugs. J. Incl. Phenom. Macrocycl. Chem., 44, 267–270 (2002).
Uchiyama, H., Tozuka, Y., Imono, M., and Takeuchi, H., Improvement of dissolution and absorption properties of poorly water-soluble drug by preparing spray-dried powders with α-glucosyl hesperidin. Int. J. Pharm., 392, 101–106 (2010).
Yamashita, K., Nakate, T., Okimoto, K., Ohike, A., Tokunaga, Y., Ibuki, R., Higaki, K., and Kimura, T., Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int. J. Pharm., 267, 79–91 (2003).
Yong, C. S., Yang, C. H., Rhee, J. D., Lee, B. J., Kim, D. C., Kim, D. D., Kim, C. K., Choi, J. S., and Choi, H. G., Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and menthol. Int. J. Pharm., 269, 169–176 (2004).
Yong, C. S., Li, D. X., Oh, D. H., Kim, J. A., Yoo, B. K., Woo, J. S., Rhee, J. D., and Choi, H. G., Retarded dissolution of ibuprofen in gelatin microcapsule by cross-linking with glutaradehyde. Arch. Pharm. Res., 29, 431–534 (2005).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Baek, H.H., Kwon, S.Y., Rho, SJ. et al. Enhanced solubility and bioavailability of flurbiprofen by cycloamylose. Arch. Pharm. Res. 34, 391–397 (2011). https://doi.org/10.1007/s12272-011-0306-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-011-0306-x