Abstract
The purpose of the present work was to investigate the interaction of drugs and octanol with hydroxypropyl β- (HPβCD) and γ- (HPγCD) cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD) and randomly methylated-β-cycoldextrin (RMβCD) and to describe the interaction by theoretical models. The poorly soluble steroid drugs progesterone, estrone and prednicarbate were used as model compounds in this study. Hexane and chloroform were also investigated in combination with HPβCD. Octanol formed a complex with all cyclodextrins and the saturation of the aqueous solution with this solvent therefore had a significant effect on the solubilization and extraction potential of cyclodextrins. Hexane had less affinity for cyclodextrins, but the drugs were poorly soluble in this solvent and it could therefore not be used in phase-distribution investigations. Previously we have derived equations that can be used to account for the competitive interaction between two guest compounds that compete for space in the cyclodextrin cavity. These equations were rearranged to calculate the complexation efficacy from phase-solubility data. An equation was derived that obtains intrinsic solubility (S 0) and intrinsic partition coefficient (P) from the slopes of the phase-solubility and phase-distribution profiles. Investigation of the data showed that the results could not be sufficiently explained by the “classical” drug/cyclodextrin complex model that recognizes the possibility of competitive interactions but ignores any contribution from higher order complexes or aggregation of the cyclodextrin complexes. Relative difference in solubilization potential of different cyclodextrins cannot be translated to relative differences in extraction efficacy. Thus, for these three steroid compounds, RMβCD and SBEβCD gave the best solubilization potential whereas the best extraction efficacy was observed with HPγCD.
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References
Connors, K.A.: Binding constants, pp. 372. John Wiley & Sons, New York (1987)
Higuchi, T., Zuck, D.A.: Solubilizing action of caffeine on benzoic acid. J. Am. Pharm. Assoc. 41(1), 176−179 (1952)
Avdeef, A.: Assesment of distribution-pH profiles. In: Pliska, V., Testa B., Van-De-Waterbeemd, H. (eds.) Lipophilicity in Drug Action and Toxicology, pp. 109–138. John Wiley & Sons, Weinhem (1996)
Masson, M., Sigurdardottir, B.V., Matthiasson, K., Loftsson, T.: Investigation of drug-cyclodextrin complexes by a phase-distribution method: some theoretical and practical considerations. Chem. Pharm. Bull. 53(8), 958–964 (2005)
Masson, M., Sigurjonsdottir, J.F. Jonsdottir, S., Loftsson, T.: Examination of F-19-NMR as a tool for investigation of drug-cyclodextrin complexes. Drug Dev. Ind. Pharm. 29(1), 107–112 (2003)
Evans, C.H., Partyka, M., Van Stam, J.: Naphthalene complexation by β-cyclodextrin: influence of added short chain branched and linear alcohols. J. Incl. Phenom. Macrocycl. Chem. 38(1–4), 381–396 (2000)
Loftsson, T., Masson, M., Brewster, M.E.: Self-association of cyclodextrins and cyclodextrin complexes. J. Pharm. Sci. 93(5), 1091–1099 (2004)
Loftsson, T., Hreinsdóttir, D., Másson, M.: Evaluation of cyclodextrin solubilization of drugs. Int. J. Pharm. 302, 18–28 (2005)
Nunez, F.A.A., Yalkowsky, S.H.: Correlation between log P and ClogP for some steroids. J. Pharm. Sci. 86(10), 1187–1189 (1997)
Hurwitz, A.R., Liu, S.T.: Determination of aqueous solubility and pka values of estrogens. J. Pharm. Sci. 66(5), 624–627 (1977)
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Másson, M., Karlsson, F.J., Valdimarsdóttir, M. et al. Cyclodextrins and the liquid-liquid phase distribution of progesterone, estrone and prednicarbate. J Incl Phenom Macrocycl Chem 57, 481–487 (2007). https://doi.org/10.1007/s10847-006-9238-3
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DOI: https://doi.org/10.1007/s10847-006-9238-3