Computational models of the gastrointestinal environment. 2. Phase behavior and drug solubilization capacity of a type I lipid-based drug formulation after digestion

Woldeamanuel A. Birru, Dallas B. Warren, Sifei Han, Hassan Benameur, Christopher J. Porter, Colin W. Pouton, David K. Chalmers

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)


Lipid based drug formulations can greatly enhance the bioavailability of poorly water soluble drugs. Following the oral administration of formulations containing tri- or diglycerides, the digestive processes occurring within the GI tract hydrolyze the glycerides to mixtures of free fatty acids and monoglycerides that are, in turn, solubilized by bile. The behavior of drugs within the resulting colloidal mixtures is currently not well characterized. This work presents matched in vitro experimental and molecular dynamics (MD) theoretical models of the gastrointestinal microenvironment containing a digested triglyceride-based (Type I) drug formulation. Both the experimental and theoretical models consist of molecular species representing bile (glycodeoxycholic acid), digested triglyceride (1:2 glyceryl-1-monooleate and oleic acid) and water. We have characterized the phase behavior of the physical system using nephelometry, dynamic light scattering and polarizing light microscopy and compared these measurements to phase behavior observed in multiple molecular dynamics (MD) simulations. Using this model microenvironment, we have investigated the dissolution of the poorly water-soluble drug danazol; experimentally, using LC-MS, and theoretically by MD simulation. The results show how the formulation lipids alter the environment of the gastrointestinal tract and improve the solubility of danazol. The MD simulations successfully reproduce the experimental results showing the utility of MD in modeling the fate of drugs after digestion of lipid-based formulations within the intestinal lumen.
Original languageEnglish
Pages (from-to)580-592
Number of pages13
JournalMolecular Pharmaceutics
Issue number3
Publication statusPublished - 6 Mar 2017


  • bile
  • digestion
  • dynamic light scattering
  • gastrointestinal tract
  • lipid-based formulation
  • molecular dynamics
  • nephelometry
  • phase behavior
  • polarizing light microscopy
  • poorly water-soluble drug

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