The AAPS Journal

, 22:3 | Cite as

Mechanistic Deconvolution of Oral Absorption Model with Dynamic Gastrointestinal Fluid to Predict Regional Rate and Extent of GI Drug Dissolution

  • Alex Yu
  • Mark J. Koenigsknecht
  • Bart Hens
  • Jason R. Baker
  • Bo Wen
  • Trachette L. Jackson
  • Manjunath P. Pai
  • William Hasler
  • Gordon L. Amidon
  • Duxin SunEmail author
Research Article


Multiple approaches such as mathematical deconvolution and mechanistic oral absorption models have been used to predict in vivo drug dissolution in the gastrointestinal (GI) tract. However, these approaches are often validated by plasma pharmacokinetic profiles, but not by in vivo drug dissolution due to the limited data available regarding the local GI environment. It is also challenging to predict and validate in vivo dissolution in different regions of the GI tract (stomach, duodenum, jejunum, and ileum). In this study, the dynamic fluid compartment absorption and transport (DFCAT) model was used to predict the in vivo dissolution profiles of ibuprofen, which was administered as an 800-mg immediate-release tablet to healthy subjects, in different regions of the GI tract. The prediction was validated with concentration time-courses of ibuprofen (BCS class 2a) in different regions of the GI tract that we have obtained over the past few years. The computational model predicted that the dissolution of ibuprofen was minimal in the stomach (2%), slightly more in the duodenum (6.3%), and primarily dissolved in the jejunum (63%) and the ileum (25%). The detailed model prediction of drug dissolution in different regions of GI can provide a quantitative reference of in vivo dissolution that may provide valuable insight in developing in vitro tests for drug product optimization and quality.


mechanistic deconvolution modeling absorption dissolution 


Funding Information

This work was partially supported by grant no. HHSF223201510157C and grant no. HHSF223201310144C by the U.S. Food and Drug Administration (FDA). Bart Hens acknowledges the financial support from the Flemish Research Council (FWO–applicant number 12R2119N).

Supplementary material

12248_2019_385_MOESM1_ESM.docx (67 kb)
ESM 1 (DOCX 67 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Alex Yu
    • 1
  • Mark J. Koenigsknecht
    • 1
  • Bart Hens
    • 1
    • 2
  • Jason R. Baker
    • 3
  • Bo Wen
    • 1
  • Trachette L. Jackson
    • 4
  • Manjunath P. Pai
    • 5
  • William Hasler
    • 3
  • Gordon L. Amidon
    • 1
  • Duxin Sun
    • 1
    • 6
    Email author
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of MichiganAnn ArborUSA
  2. 2.Department of Pharmaceutical and Pharmacological SciencesKU LeuvenLeuvenBelgium
  3. 3.Department of Internal Medicine, College of MedicineUniversity of MichiganAnn ArborUSA
  4. 4.Department of Mathematics, College of Literature, Science, and the ArtsUniversity of MichiganAnn ArborUSA
  5. 5.Department of Clinical Pharmacy, College of PharmacyUniversity of MichiganAnn ArborUSA
  6. 6.North Campus Research Complex (NCRC)Ann ArborUSA

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