Abstract
The aim of this study was to investigate the characteristics ofhydroxypropyl-β-cyclodextrin (HPCD) on the solubility,photostability and dissolution of carprofen (CP). It was found that the solubility of carprofen increased 52-fold when16% HPCD was added to H2O (w/v). The phase-solubility diagram revealed the formation of a 1 : 1 inclusion complex of CP-HPCD with a stability constant (ks) of 487 M-1. Formation of the inclusion complex of CP-HPCD was analyzed using differential scanning calorimetry (DSC). Changes in chemical shifts of the 1H-nuclear magnetic resonance spectra of CP-HPCD demonstrated that the inclusion site of CP by HPCD was carbazolyl aromatic ring skeleton rather thanthe side chain of propanoic acid. The photostability study revealed that theCP-HPCD complex could not significantly decrease the rate of photodegradation of CP, implying that the rate-determining step of CP mainly occurredat the side chain. The dissolution rates of CP were significantly enhanced as the proportions of HPCD increasedin the prepared discs. The dissolution of the physical mixture (in a 1 : 3 molarratio) increased by about 6-fold in comparison with the parent drug. The improvement of wettability and solubility of CP by complexing to HPCD was reflected in theenhanced dissolution rate.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
T.F. Yu and J. Perel: J. Clin. Pharmacol. 20, 447 (1980).
R.L. Williams, D.E. Furst, H.G. Mandel, D. Nicoll, J.J. Konikoff, and L.Z. Benet: J. Clin. Pharmacol. 21, 493 (1981).
W.M. O’Brien and G.F. Bagby: Pharmacotherapy 7, 16 (1987).
M.S. Islam and M.M. Narurkar: Drug Dev. Ind. Pharm. 17, 1229 (1991).
A. Shiotani, Y. Yamaoka, H.M. El-Zimaity, M.A. Saeed, W.A. Qureshi, and D.Y. Graham: Dig. Dis. Sci. 47, 38 (2002).
J.L. Wallace, W. McKnight, B.K. Reuter, and N. Vergnolle: Gastroenterology 119, 706 (2000).
N. Erden and N. Celebi: Int. J. Pharm. 48, 83 (1988).
L. Becker, B. Eberlein-konig, and B. Przybilla: Acta Derm. Venereol. 76, 337 (1996).
G.D. Guidi, R. Chillemi, L.L. Costanzo, S. Giuffrida, and G. Condorelli: J. Photochem. Photobiol. B: Biols. 17, 239 (1993).
O. Bekers, E.V. Uijtendaal, J.H. Beijnen, A. Bult, and W.J.M. Underberg: Drug Dev. Ind. Pharm. 17, 1503 (1991).
D. Duchêne and D. Wouessidjewe: Drug Dev. Ind. Pharm. 16, 2487 (1990).
O. Bekers, J.H. Beijnen, B.J. Vis, A. Suenaga, M. Otagiri, A. Bult, and W.J.M. Underberg: Int. J. Pharm. 72, 123 (1991).
S. Choudhury and K.F. Nelson: Int. J. Pharm. 85, 175 (1992).
M. Yamamoto, A. Yoshida, F. Hirayama, and K. Uekema: Int. J. Pharm. 49, 163 (1989).
A.B. Wu, C.Y. Chen, S.D. Chu, Y.C. Tsai, and F.A. Chen: J. Chromatogr. Sci. 39, 7 (2001).
T. Higuchi and K.A. Connors: Anal. Chem. Instrum. 4, 117 (1965).
J. Szejtli: Pharm. Technol. 36 (1991).
P.S. Manchand, D.L. Coffen, P.S. Belica, F. Wong, H.S.Wong, and L. Berger: Heterocycles 39, 833 (1994).
K. Harata: J. Chem. Soc., Chem. Commun. 546 (1993).
K. Uekema, F. Hirayama, T. Imai, M. Otagiri, and K. Harata: Chem. Pharm. Bull. 31, 3363 (1983).
M.A. Hassan, M.S. Suleiman, and N.M. Najib: Int. J. Pharm. 58, 19 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chen, FA., Wu, AB. & Chen, CY. Inclusion Complex of Carprofen with Hydroxypropyl-β-cyclodextrin. Journal of Inclusion Phenomena 46, 111–115 (2003). https://doi.org/10.1023/A:1025699207208
Issue Date:
DOI: https://doi.org/10.1023/A:1025699207208