Skip to main content
SpringerLink
Log in

In Vitro System to Evaluate Oral Absorption of Poorly Water-Soluble Drugs: Simultaneous Analysis on Dissolution and Permeation of Drugs

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. The aim of the present work was to develop a new in vitro system to evaluate oral absorption of poorly water-soluble drugs by utilizing Caco-2 monolayers.

Methods. Caco-2 monolayer was mounted between side-by-side chambers, which enabled the simultaneous assay of dissolution and permeation of drugs (dissolution/permeation system; D/P system). Apical and basal sides of the chamber were filled with buffer solutions. Drugs were applied to the apical side as powder, suspension, or solution, and then, the permeated amounts into the basal side were monitored for 2 h. At the same time, dissolved amounts of drugs at the apical side were detected. The amount of drug applied to the D/P system was based on its in vivo clinical dose.

Results. Sodium taurocholate (5 mM, apical side) and bovine serum albumin (4.5% w/v, basal side) increased the permeated amount of poorly water-soluble drugs. Both additives were considered to be effective at mimicking in vivo conditions of intestinal drug absorption. From the correlation between the permeated amount of 13 drugs (% dose/2 h) in the D/P system and their percentage dose absorbed in humans in vivo, this system was found to be useful in evaluating oral absorption of poorly water-soluble drugs.

Conclusions. With attempts made to mimic the physiologic conditions of the human GI tract, in vivo oral absorption of drugs was quantitatively assessed in the D/P system in vitro. This system is quite useful to predict the oral absorption of poorly water-soluble drugs after administration as solid dosage forms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. G. L. Amidon, Oh Doo-Man, and R. L. Curl. Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: A mathematical model. Pharm. Res. 10:264-270 (1993).

    Google Scholar 

  2. G. L. Amidon, H. Lennernas, V. P. Shah, and J. 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).

    Google Scholar 

  3. I. J. Hidalgo, T. J. Raub, and R. T. Borchardt. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology. 96:736-749 (1989).

    Google Scholar 

  4. P. Artursson and J. Karlsson. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 175:880-885 (1991).

    Google Scholar 

  5. S. Yamashita, Y. Tanaka, Y. Endoh, Y. Taki, T. Sakane, T. Nadai, and H. Sezaki. Analysis of drug permeation across Caco-2 monolayer: implication for predicting in vivo drug absorption. Pharm. Res. 14:486-491 (1997).

    Google Scholar 

  6. J. D. Irvine, L. Takahashi, K. Lockhart, J. Cheong, J. W. Tolan, H. E. Selick, and J. R. Grove. MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. J. Pharm. Sci. 88:28-33 (1999).

    Google Scholar 

  7. R. Palma, N. Vidon, G. Houin, A. Pfeiffer, M. Rongier, J. Barre, and J. J. Bernier. Influence of bile salts and lipids on intestinal absorption of griseofulvin in man. Eur. J. Clin. Pharmacol. 31:319-325 (1986).

    Google Scholar 

  8. W. N. Charman, M. C. Rogge, A. W. Boddy, and B. M. Berger. Effect of food and a monoglyceride emulsion formulation on danazol bioavailability. J. Clin. Pharmacol. 33:381-386 (1993).

    Google Scholar 

  9. H. Lange, R. Eggers, and J. Bircher. Increased systemic availability of albendazole when taken with a fatty meal. Eur. J. Clin. Pharmacol. 34:315-317 (1988).

    Google Scholar 

  10. P. C. Sheen, S. I. Kim, J. J. Petillo, and A. T. Serajuddin. Bioavailability of a poorly water-soluble drug from tablet and solid dispersion in humans. J. Pharm. Sci. 80:712-714 (1991).

    Google Scholar 

  11. M. Winkler, B. Ringe, K. Schneider, A. Maibucher, L. Farber, H. Wietholtz, M. Manns, and R. Pichlmayr. Enhanced bioavailability of cyclosporine using a new oral formulation (Sandimmun optoral) in a liver-grafted patient with severe cholestasis. Transpl. Int. 7:147-148 (1994).

    Google Scholar 

  12. J. B. Dressman and C. Reppas. In vitro–in vivo correlations for lipophilic, poorly water-soluble drugs. Eur. J. Pharm. Sci. 11(Suppl. 2):S73-S80 (2000).

    Google Scholar 

  13. M. J. Ginski, R. Taneja, and J. E. Polli. Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 System. AAPS PharmSci. 1:E3, 1-12 (1999).

    Google Scholar 

  14. M. J. Ginski and J. E. Polli. Prediction of dissolution–absorption relationships from a dissolution/Caco-2 system. Int. J. Pharm. 177:117-125 (1999).

    Google Scholar 

  15. M. Kobayashi, N. Sada, M. Sugawara, K. Iseki, and K. Miyazaki. Development of a new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract. Int. J. Pharm. 221:87-94 (2001).

    Google Scholar 

  16. T. L. Peeters, G. Vantrappen, and J. Janssens. Bile acid output and the interdigestive migrating motor complex in normal and in cholecystectomy patients. Gastroenterology. 79:678-681 (1980).

    Google Scholar 

  17. A. Tangerman, A. van Schai, and E. W. van der Hoek. Analysis of conjugated and unconjugated bile acids in serum and jejunal fluid of normal subjects. Clin. Chim. Acta 159:123-132 (1986).

    Google Scholar 

  18. T. Kimura, H. Sezaki, and K. Kakemi. Effect of bile salts on the gastrointestinal absorption of drugs. IV. Site of intestinal absorption of sodium taurocholate and its consequence on drug absorption in the rat. Chem. Pharm. Bull. 20:1656-1662 (1972).

    Google Scholar 

  19. S. Yamashita, T. Furubayashi, M. Kataoka, T. Sakane, H. Sezaki, and H. Tokuda. Optimized condition for prediction of intestinal drug permeability using Caco-2 cells. Eur. J. Pharm. Sci. 10:195-204 (2000).

    Google Scholar 

  20. S. S. Davis, J. G. Hardy, and J. W. Fara. Transit of pharmaceutical dosage forms through the small intestine. Gut 27:886-892 (1986).

    Google Scholar 

  21. S. Yamashita, K. Konishi, Y. Yamazaki, Y. Taki, T. Sakane, H. Sezaki, and Y. Furuyama. New and better protocols for a short-term Caco-2 cell culture system. J. Pharm. Sci. 91:669-679 (2002).

    Google Scholar 

  22. J. B. Dressman, G. L. Amidon, C. Reppas, and V. P. Shah. Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharm. Res. 15:11-22 (1998).

    Google Scholar 

  23. E. Galia, E. Nicolaides, D. Horter, R. Lobenberg, C. Reppas, and J. B. Dressman. Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs. Pharm. Res. 15:698-705 (1998).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Setsunan University, Nagaotoge-cho 45-1, Hirakata, Osaka, 573-0101, Japan

    Makoto Kataoka, Yoshie Masaoka, Yukako Yamazaki, Toshiyasu Sakane, Hitoshi Sezaki & Shinji Yamashita

Authors
  1. Makoto Kataoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshie Masaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yukako Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshiyasu Sakane
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hitoshi Sezaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shinji Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Makoto Kataoka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kataoka, M., Masaoka, Y., Yamazaki, Y. et al. In Vitro System to Evaluate Oral Absorption of Poorly Water-Soluble Drugs: Simultaneous Analysis on Dissolution and Permeation of Drugs. Pharm Res 20, 1674–1680 (2003). https://doi.org/10.1023/A:1026107906191

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026107906191

Search

Navigation