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The Effects of Food on the Dissolution of Poorly Soluble Drugs in Human and in Model Small Intestinal Fluids

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This study was conducted to determine the effect of food on drug solubility and dissolution rate in simulated and real human intestinal fluids (HIF).


Dissolution rate obtained via the rotating disk method and saturation solubility studies were carried out in fed and fasted state HIF, fed dog (DIF), and simulated (FeSSIF) intestinal fluid for six aprotic low solubility drugs. The intestinal fluids were characterized with respect to physical–chemical characteristics and contents.


Fed HIF provided a 3.5- to 30-times higher solubility compared to fasted HIF and FeSSIF, whereas fed DIF corresponded well (difference of less than 30%) to fed HIF. The increased solubility of food could mainly be attributed to dietary lipids and bile acids. The dissolution rate was also 2 to 7 times higher in fed HIF than fasted HIF. This was well predicted by both DIF and FeSSIF (difference of less than 30%).


Intestinal solubility is higher in fed state compared to fasted state. However, the dissolution rate does not increase to the same extent. Dog seems to be a good model for man with respect to dissolution in the small intestine after intake of a meal, whereas FeSSIF is a poorer means of determining intestinal saturation solubility in the fed state.

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biopharmaceutical classification system

C s :

saturation solubility


coefficient of variation


dog intestinal fluid

D n :

dissolution number

D o :

dose number


evaporative light scattering


fed simulated small intestinal fluid

H acc :

number of hydrogen acceptors

H don :

number of hydrogen donors


human intestinal fluid

ΔH m :

change in melting entrophy


high-performance liquid chromatography



logP :

octanol/water patition coefficient


limit of quantification

M 0 :

the dose drug administered

M w :

molecular weight


mass to charge


partial least squares

S aq :

aqueuos solubility

t diss :

the time required for one particle of the drug to dissolve

T m :

melting point

t res :

the mean residence time



V 0 :

the initial gastric volume


  1. S. M. Caliph W. N. Charman C. J. Porter (2000) ArticleTitleEffect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats J. Pharm. Sci. 89 IssueID8 1073–1084 Occurrence Handle10906731 Occurrence Handle10.1002/1520-6017(200008)89:8<1073::AID-JPS12>3.0.CO;2-V Occurrence Handle1:CAS:528:DC%2BD3cXmtVWmsb4%3D

    Article  PubMed  CAS  Google Scholar 

  2. T. R. Bates P. J. Carrigan (1975) ArticleTitleApparent absorption kinetics of micronized griseofulvin after its oral administration on single and multiple-dose regiments to rats as a corn oil-in-water emulsion and aqueous suspension J. Pharm. Sci. 64 1475–1481 Occurrence Handle1185560 Occurrence Handle1:CAS:528:DyaE2MXlvVegsbg%3D

    PubMed  CAS  Google Scholar 

  3. R. G. Crounse (1963) ArticleTitleEffective use of griseofulvin Arch. Dermatol. 87 176–180 Occurrence Handle14024023 Occurrence Handle1:STN:280:DyaF383hsF2qug%3D%3D

    PubMed  CAS  Google Scholar 

  4. W. N. Charman M. C. Rogge A. W. Boddy B. M. Berger (1993) ArticleTitleEffect of food and a monoglyceride emulsion formulation on danazol bioavailability J. Clin. Pharmacol. 33 381–386 Occurrence Handle8473554 Occurrence Handle1:CAS:528:DyaK2cXivVSjtbw%3D

    PubMed  CAS  Google Scholar 

  5. W. N. Charman M. C. Rogge A. W. Boddy W. H. Barr B. M. Berger (1993) ArticleTitleAbsorption of danazol after administration to different sites of the gastrointestinal tract and the relationship to single- and double peak phenomena in the plasma profiles J. Clin. Pharmacol. 33 1207–1213 Occurrence Handle8126256 Occurrence Handle1:STN:280:DyaK2c7nt1Wjug%3D%3D

    PubMed  CAS  Google Scholar 

  6. V. H. Sunesen B. L. Pedersen H. G. Kristensen A. Müllerz (2005) ArticleTitleIn vivo in vitro correlations for a poorly soluble drug using the flow-through dissolution method with biorelevant dissolution media Eur. J. Pharm. Sci. 24 305–313 Occurrence Handle15734297 Occurrence Handle1:CAS:528:DC%2BD2MXhslWmsLc%3D

    PubMed  CAS  Google Scholar 

  7. B. Borgström (1967) ArticleTitlePartition of lipids between emulsified oil and micellar phases of glyceride-bile salt dispersions J. Lipid Res. 8 IssueID6 598–608 Occurrence Handle6057490

    PubMed  Google Scholar 

  8. O. Hernell J. E. Staggers M. C. Carey (1990) ArticleTitlePhysical–chemical behaviour of dietary and biliary lipids during intestinal digestion and absorption: 2. Phase analyses and aggregation states of luminal lipids during duodenal fat digestion in healthy adult beings Biochemistry 29 2041–2056 Occurrence Handle2328238 Occurrence Handle10.1021/bi00460a012 Occurrence Handle1:CAS:528:DyaK3cXpsF2rtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  9. T. Bates M. Gibaldi J. Kanig (1966) ArticleTitleSolubilizing properties of bile salt solutions J. Pharm. Sci. 55 191–199 Occurrence Handle5923268 Occurrence Handle1:CAS:528:DyaF28XltFajtg%3D%3D

    PubMed  CAS  Google Scholar 

  10. B. L. Pedersen A. Müllerz H. Brondsted H. G. Kristensen (2000) ArticleTitleA comparison of the solubility of danazol in human and simulated gastrointestinal fluids Pharm. Res. 17 IssueID7 891–894 Occurrence Handle10990211 Occurrence Handle10.1023/A:1007576713216 Occurrence Handle1:CAS:528:DC%2BD3cXms1Wlt7w%3D

    Article  PubMed  CAS  Google Scholar 

  11. L. J. Naylor V. Bakatselou N. Rodríguez-Hornedo N. D. Weiner J. B. Dressman (1995) ArticleTitleDissolution of steroids in bile salt solutions is modified by the presence of lecithin Eur. J. Pharm. Biopharm. 41 IssueID6 346–353 Occurrence Handle1:CAS:528:DyaK28Xlsl2quw%3D%3D

    CAS  Google Scholar 

  12. N. H. Zangenberg A. Müllerz H. G. Kristensen L. Hovgaard (2001) ArticleTitleA dynamic in vitro lipolysis model: II. Evaluation of the model Eur. J. Pharm. Sci. 14 237–244 Occurrence Handle11576829 Occurrence Handle1:CAS:528:DC%2BD3MXntV2hs70%3D

    PubMed  CAS  Google Scholar 

  13. A. M. Kaukonen B. J. Boyd C. J. H. Porter W. N. Charman (2004) ArticleTitleDrug solubilization behaviour during in vitro digestion of simple triglyceride lipid solution formulations Pharm. Res. 21 IssueID2 245–253 Occurrence Handle15032305 Occurrence Handle1:CAS:528:DC%2BD2cXhtlWqsbs%3D

    PubMed  CAS  Google Scholar 

  14. A. M. Kaukonen B. J. Boyd W. N. Charman C. J. Porter (2004) ArticleTitleDrug solubilization behaviour during in vitro digestion of suspension formulations of poorly water-soluble drugs in triglyceride lipids Pharm. Res. 21 IssueID2 254–260 Occurrence Handle15032306 Occurrence Handle1:CAS:528:DC%2BD2cXhtlWqsbo%3D

    PubMed  CAS  Google Scholar 

  15. L. Sek C. J. Porter A. M. Kaukonen W. N. Charman (2002) ArticleTitleEvaluation of in vitro digestion profiles of long and medium chain glycerides and the phase behaviour of their lipolytic products J. Pharm. Pharmacol. 54 IssueID1 29–41 Occurrence Handle11833493 Occurrence Handle10.1211/0022357021771896 Occurrence Handle1:CAS:528:DC%2BD38XhtlWru78%3D

    Article  PubMed  CAS  Google Scholar 

  16. G. A. Kossena B. J. Boyd C. J. H. Porter W. N. Charman (2003) ArticleTitleSeparation and characterisation of the colloidal phases produced in digestion of common formulation lipids and assessment of their impact on the apparent solubility of selected poorly water-soluble drugs J. Pharm. Sci. 92 IssueID3 634–648 Occurrence Handle12587125 Occurrence Handle10.1002/jps.10329 Occurrence Handle1:CAS:528:DC%2BD3sXitVajsr8%3D

    Article  PubMed  CAS  Google Scholar 

  17. J. O. Christensen K. Schultz B. Mollgaard H. G. Kristensen A. Müllertz (2004) ArticleTitleSolubilisation of poorly water-soluble drugs during in vitro lipolysis of medium- and long-chain triacylglycerol Eur. J. Pharm. Sci. 23 287–296 Occurrence Handle15489130 Occurrence Handle1:CAS:528:DC%2BD2cXos1ersbw%3D Occurrence Handle10.1016/j.ejps.2004.08.003

    Article  PubMed  CAS  Google Scholar 

  18. V. Bakatselou R. C. Oppenheim J. B. Dressman (1991) ArticleTitleSolubilization and wetting effects of bile salts on the dissolution of steroids Pharm. Res. 8 IssueID12 1461–1469 Occurrence Handle1808607 Occurrence Handle10.1023/A:1015877929381 Occurrence Handle1:CAS:528:DyaK38Xks1WntQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  19. J. H. Smidt Particlede J. C. A. Offringa D. J. A. Crommelin (1991) ArticleTitleDissolution rate of griseofulvin in bile salt solutions J. Pharm. Sci. 80 IssueID4 399–401 Occurrence Handle1865343

    PubMed  Google Scholar 

  20. W. I. Higuchi S. Prakongpan V. Surpuriya F. Young (1972) ArticleTitleCholesterol dissolution rate in micellar bile acid solutions: retarding effect of added lecithin Science 178 633–634 Occurrence Handle5086400 Occurrence Handle1:CAS:528:DyaE3sXjvVCktw%3D%3D

    PubMed  CAS  Google Scholar 

  21. E. Galia E. Nicolaides D. Hörter R. Löbenberg C. Reppas J. B. Dressman (1998) ArticleTitleEvaluation of various dissolution media for predicting in vivo performance of class I and II drugs Pharm. Res. 15 IssueID5 698–705 Occurrence Handle9619777 Occurrence Handle10.1023/A:1011910801212 Occurrence Handle1:CAS:528:DyaK1cXjtlWhsL8%3D

    Article  PubMed  CAS  Google Scholar 

  22. E. S. Kostewicz A. S. Carlsson G. Hanisch K. Krumkühler R. G. Nilsson L. Löfgren B. Abrahamsson (2002) ArticleTitleComparison of dog and human intestinal fluid and its impact on solubility estimations Eur. J. Pharm. Sci. 17 IssueID1 S1–S148

    Google Scholar 

  23. B. L. Pedersen H. Brondsted H. Lennernäs F. N. Christensen A. Müllertz H. G. Kristensen (2000) Pharm. Res. 17 IssueID2 183–189 Occurrence Handle10751033 Occurrence Handle10.1023/A:1007517414200 Occurrence Handle1:CAS:528:DC%2BD3cXitVOqurw%3D

    Article  PubMed  CAS  Google Scholar 

  24. H. Lennernas Ö. Ahrenstedt R. Hällgren L. Knutsson M. Ryde L. Paalzow (1992) ArticleTitleRegional jejunal perfusion, a new in vivo approach to study oral drug absorption in man Pharm. Res. 9 1243–1251 Occurrence Handle1448420 Occurrence Handle1:STN:280:DyaK3s%2FnvFajsA%3D%3D

    PubMed  CAS  Google Scholar 

  25. L. Knutson B. Odlind R. Hallgren (1989) ArticleTitleA new technique for segmental jejunal perfusion in man Am. J. Gastroenterol. 84 1278–1284 Occurrence Handle2801679 Occurrence Handle1:STN:280:DyaK3c%2FitlCgtA%3D%3D

    PubMed  CAS  Google Scholar 

  26. A. Lindahl A. L. Ungell L. Knutsson H. Lennernas (1997) ArticleTitleCharacterisation of fluids from the stomach and proximal jejunum in men and women Pharm. Res. 14 IssueID4 497–502 Occurrence Handle9144738 Occurrence Handle10.1023/A:1012107801889 Occurrence Handle1:CAS:528:DyaK2sXjtVWrsbk%3D

    Article  PubMed  CAS  Google Scholar 

  27. Y. Shi P. Burn (2004) ArticleTitleLipid metabolic enzymes: emerging drug targets for the treatment of obesity Nat. Rev. 3 695–710 Occurrence Handle1:CAS:528:DC%2BD2cXmtVOhtL0%3D

    CAS  Google Scholar 

  28. S. D. Mithani V. Bakatselou C. N. TenHoor J. B. Dressman (1996) ArticleTitleEstimation of the increase in solubility of drugs as a function of bile salt concentration Pharm. Res. 13 163–167 Occurrence Handle8668668 Occurrence Handle10.1023/A:1016062224568 Occurrence Handle1:CAS:528:DyaK28XhtFajs7k%3D

    Article  PubMed  CAS  Google Scholar 

  29. A. Scholz B. Abrahamsson S. M. Diebold E. Kostewicz B. I. Polentarutti A. L. Ungell J. B. Dressman (2002) ArticleTitleInfluence of hydrodynamics and particle size on the absorption of felodipine in labradors Pharm. Res. 19 IssueID1 42–46 Occurrence Handle11837699 Occurrence Handle10.1023/A:1013651215061 Occurrence Handle1:CAS:528:DC%2BD38XhtVSmsb0%3D

    Article  PubMed  CAS  Google Scholar 

  30. T. Gramatte (1994) ArticleTitleGriseofulvin absorption from different sites in the human small intestine Biopharm. Drug Dispos. 15 IssueID9 747–759 Occurrence Handle7888603 Occurrence Handle1:CAS:528:DyaK2MXisFOjsLg%3D

    PubMed  CAS  Google Scholar 

  31. D. B. Jack (1992) Handbook of Clinical Pharmacokinetic Data MacMillan Basingstoke

    Google Scholar 

  32. G. L. Amidon H. Lennernas V. P. Shah J. R. Crison (1995) ArticleTitleA theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability Pharm. Res. 12 IssueID3 413–420 Occurrence Handle7617530 Occurrence Handle10.1023/A:1016212804288 Occurrence Handle1:CAS:528:DyaK2MXksVGqur8%3D

    Article  PubMed  CAS  Google Scholar 

  33. W. L. Jorgensen (1998) BOSS—biochemical and organic simulation system P. v. R. Schleyer (Eds) The Encyclopedia of Computational Chemistry Wiley Athens, USA 3281–3285

    Google Scholar 

  34. L. Zhou D. Tan J. Theng L. Lim Y. Liu K. Lam (2001) ArticleTitleOptimized analytical method for cyclosporin A by high-performance liquid chromatography-electrospray ionization mass spectrometry J. Chromatogr., B 754 201–207 Occurrence Handle1:CAS:528:DC%2BD3MXit1Wnuro%3D

    CAS  Google Scholar 

  35. D. Hörter J. B. Dressmann (1997) ArticleTitleInfluence of physicochemical properties on dissolution of drugs in the gastrointestinal tract Adv. Drug Deliv. Rev. 25 IssueID1 3–14

    Google Scholar 

  36. W. Nernst E. Brunner (1904) ArticleTitleTheorie der reaktionsgeschwindigkeit in heterogenen systemen Z. Phys. Chem. 47 52–110 Occurrence Handle1:CAS:528:DyaD28XhtVCj

    CAS  Google Scholar 

  37. P. Singh S. J. Desai D. R. Flanagan A. P. Simonelli W. I. Higuchi (1968) ArticleTitleMechanistic study of the influence of micelle solubilization and hydrodynamic factors on the dissolution rate of solid drugs J. Pharm. Sci. 57 IssueID6 959–965 Occurrence Handle5671343 Occurrence Handle1:CAS:528:DyaF1cXkt1Wrur0%3D

    PubMed  CAS  Google Scholar 

  38. B. Agoram W. S. Woltosz M. B. Bolger (2001) ArticleTitlePredicting the impact of physiological and biochemical processes on oral drug bioavailability Adv. Drug Deliv. Rev. 50 IssueID1 S41–S67 Occurrence Handle11576695 Occurrence Handle1:CAS:528:DC%2BD3MXntVWku74%3D

    PubMed  CAS  Google Scholar 

  39. S. Klein J. Butler J. M. Hempenstall C. Reppas J. B. Dressman (2004) ArticleTitleMedia to simulate the postprandial stomach: I. Matching the physicochemical characteristics of standard breakfasts J. Pharm. Pharmacol. 56 605–610 Occurrence Handle15142337 Occurrence Handle10.1211/0022357023367 Occurrence Handle1:CAS:528:DC%2BD2cXkslyqur0%3D

    Article  PubMed  CAS  Google Scholar 

  40. P. H. J. M. Dunselman B. Edgar (1991) ArticleTitleFelodipine clinical pharmacokinetics Clin. Pharmacokinet. 21 IssueID6 418–430 Occurrence Handle1782737 Occurrence Handle1:STN:280:DyaK387ksFyrsA%3D%3D

    PubMed  CAS  Google Scholar 

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We are thankful to Dr. Ralf Nilsson, Dr. Lars Löfgren, and Dr. Göran Hansson for their excellent technical assistance in the lipid analysis, and Angela Ku for the PLS analysis.

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Correspondence to Bertil Abrahamsson.

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Persson, E.M., Gustafsson, AS., Carlsson, A.S. et al. The Effects of Food on the Dissolution of Poorly Soluble Drugs in Human and in Model Small Intestinal Fluids. Pharm Res 22, 2141–2151 (2005).

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