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Prediction of Intestinal Drug Absorption Properties by Three-Dimensional Solubility Parameters

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Abstract

Purpose. The purpose of this study was to investigate the use of solubility parameters for the prediction of gastrointestinal absorption sites and absorption durations of drugs.

Methods. Three-dimensional solubility parameters of drug substances were calculated using an advanced parameter set based on the group contribution methods of Fedors and Van Krevelen/Hoftyzer. The results of the calculations were illustrated via Bagley diagram and related to absorption data reported in the literature.

Results. Solubility parameters of drugs which are known to be absorbed over a long period in human's digestive tract were found in a limited area within the Bagley diagram. From the three-dimensional solubility parameters of these substances, a region for optimal absorption with the centre coordinates δv = 20.3 (J ⋅ cm−3)0.5 and δh = 11.3 (J ⋅ cm−3)0.5 could be derived. Drugs with absorption sites along the whole gastrointestinal tract were found in this area. Drugs which are preferably absorbed from upper parts of the intestine are located in another typical region with partial solubility parameters δh of more than 17 (J ⋅ cm−3)0.5.

Conclusions. The method which is presented in this paper appears as a simple but effective method to estimate the absorption behaviour of new substances in drug research and development.

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REFERENCES

  1. W. I. Higuchi, N. F. H. Ho, J. Y. Park, and I. Komiya. Rate-limiting steps and factors in drug absorption. In L. F. Prescott, W. S. Nimmo. Drug absorption, MTP Press Limited, Lancaster UK, 1981, pp. 35–60.

    Google Scholar 

  2. N. Rouge, P. Buri, and E. Doelker. Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery. Int. J. Pharm. 136:117–139 (1996).

    Google Scholar 

  3. A. Tsuji and I. Tamai. Carrier-mediated intestinal transport of drugs. Pharm. Res. 13:963–977 (1996).

    PubMed  Google Scholar 

  4. G. L. Amidon, H. Lennernäs, V. P. Shah, and J. R. Crison. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12:413–420 (1995).

    PubMed  Google Scholar 

  5. L. X. Yu, E. Lipka, J. R. Crison, and G. L. Amidon. Transport approaches to the biopharmaceutical design of oral drug delivery systems: prediction of intestinal absorption. Adv. Drug Deliver. Rev. 19:359–376 (1996).

    Google Scholar 

  6. G. M. Grass. Simulation models to predict oral drug absorption from in vitro data. Adv. Drug Deliver. Rev. 23:199–219 (1997).

    Google Scholar 

  7. C. Hansch and J. M. Clayton. Lipophilic character and biological activity of drugs II: The parabolic case. J. Pharm. Sci. 62:1–21 (1973).

    Google Scholar 

  8. N. El-Tayar, R.-S. Tsai, B. Testa, P.-A. Carrupt, and A. Leo. Partitioning of solutes in different solvent systems: The contribution of hydrogen-bonding capacity and polarity. J. Pharm. Sci. 80:590–598 (1991).

    PubMed  Google Scholar 

  9. C. M. Hansen. The universality of the solubility parameter. Ind. Eng. Chem. Res. Devel. 8:2–11 (1969).

    Google Scholar 

  10. B. Testa, P.-A. Carrupt, P. Gaillard, F. Billois, and P. Weber. Lipophilicity in molecular modeling. Pharm. Res. 13:335–343 (1996).

    PubMed  Google Scholar 

  11. N. Bodor and M.-J. Huang. A new method for the estimation of the aqueous solubility of organic compounds. J. Pharm. Sci. 81:954–960 (1992).

    PubMed  Google Scholar 

  12. J. L. Mokrosz, B. Duszynska, and L. Strekowski. Topological inidices in correlation analysis. Part 3: The modelling of hydrophobic properties using molecular connectivity and shape indices. Pharmazie 47:538–541 (1992).

    Google Scholar 

  13. K. Palm, P. Stenberg, K. Luthmann, and P. Artursson. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 14:568–571 (1997).

    PubMed  Google Scholar 

  14. R. Gröning and F.-J. Braun. Threedimensional solubility parameters and their use in characterising the permeation of drugs through the skin. Pharmazie 51:337–341 (1996).

    PubMed  Google Scholar 

  15. R. Gröning, W. Sakran, F.-J. Braun, M. S. Adel, A: Abd El-Bary, and M. F. El-Miligi. Rectal absorption of drugs—indirect characterisation of the rectal membrane using the Bagley diagram and in vivo drug absorption data. Eur. J. Pharm. Biopharm. 42(Suppl.):55 S (1996).

    Google Scholar 

  16. R. F. Fedors. A method for estimating both the solubility parameters and molar volumes of liquids. Polymer Engin. Sci. 14:147–154 (1974).

    Google Scholar 

  17. D. W. Van Krevelen and P. J. Hoftyzer. Properties of polymers. Their estimation and correlation with chemical structures. Elsevier, Amsterdam, 1976.

    Google Scholar 

  18. J. Breitkreutz, J. Bolten, and R. Gröning. Publication in progress. The computer program SPWin 2.1 requires Microsoft Windows™ 3.1 or higher. It is available by correspondance to the author.

  19. A. F. M. Barton. Solubility parameters. Chem. Rev. 75:731–753 (1975).

    Google Scholar 

  20. E. B. Bagley, T. P. Nelson, and J. M. Scigliano. Three-dimensional solubility parameters and their relationship to internal pressure measurements in polar and hydrogen bonding solvents. J. Paint Technol. 43:35–42 (1971).

    Google Scholar 

  21. R. Gröning and G. Heun. Charakterisierung der Arzneistoffabsorption aus dem Gastrointestinaltrakt mit Hilfe der numerischen Dekonvolution. Pharm. Acta Helv. 64:71–75 (1989).

    PubMed  Google Scholar 

  22. A. H. Staib. Methods used to investigate drug absorption in the colon: A review. Workshop “Colon-Resorption und Colon-Targeting”. Düsseldorf, 1996.

  23. J. J. O'Brien and D. M. Campoli-Richards. Acyclovir—an updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 37:233–309 (1989).

    PubMed  Google Scholar 

  24. J. M. Cedarbaum. Clinical Pharmacokinetics of Anti-Parkinsonian Drugs. Clin. Pharmacokin. 13:141–178 (1987).

    Google Scholar 

  25. W. H. Barr, E. M. Zola, E. L. Candler, S. M. Hwang, A. V. Tendolkar, R. Shamburek, B. Parker, M. D. Hilty. Differential absorption of amoxicillin from the human small and large intestine. Clin. Pharmacol. Therap. 56:279–285 (1994).

    Google Scholar 

  26. J. Drewe, C. Beglinger, and T. Kissel. The absorption site of cyclosporin in the human gastrointestinal tract. Br. J. Clin. Pharmac. 30:35–39 (1992).

    Google Scholar 

  27. D. Brockmeier, H. G. Grigleit, H. Leonhardt. The absorption of piretanide from the gastro-intestinal tract is site-dependent. Eur. J. Clin. Pharmacol. 30:79–82 (1986).

    PubMed  Google Scholar 

  28. S. S. Davis, N. Washington, A. H. Short, V. A. John, P. Lloyd, S. M. Walker. Relationship between the rate of appearance of oxprenolol in the systemic circulation and the location of an oxprenolol oros 16/260 drug delivery system within the gastrointestinal tract as determined by scintigraphy Br. J. Clin. Pharmac. 26:435–443 (1988).

    Google Scholar 

  29. W. M. Meylan and P. H. Howard. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84:83–92 (1995).

    PubMed  Google Scholar 

  30. R. A. Conradi, P. S. Burton, and R. T. Borchardt. Physicochemical and biological factors that influence a drug's cellular permeability by passive diffusion. In V. Pliska, B. Testa, H. van de Waterbeemd, Lipophilicity in drug action and toxicology, VCH Verlagsgesellschaft, Weinheim, Germany, 1996, pp. 233–252.

    Google Scholar 

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  1. Institute for Pharmaceutical Technology, Westphalien Wilhelms University, Münster, Germany

    Jörg Breitkreutz

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  1. Jörg Breitkreutz
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Breitkreutz, J. Prediction of Intestinal Drug Absorption Properties by Three-Dimensional Solubility Parameters. Pharm Res 15, 1370–1375 (1998). https://doi.org/10.1023/A:1011941319327

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