title: Supersaturation in human gastric fluids.
abstract: OBJECTIVE
  The current study reports on supersaturation, precipitation and excipient mediated precipitation inhibition of five poorly soluble drugs (loviride, glibenclamide, itraconazole, danazol, and etravirine) in human and simulated gastric fluids.
  
  
  METHODS
  Upon induction of supersaturation in human gastric fluids (HGFs), simulated gastric fluid (SGF), and fasted state simulated gastric fluid (FaSSGF) using a solvent shift method, supersaturation and precipitation were assessed as a function of time. In addition, the precipitation inhibitory capacity of three polymers (Eudragit® E PO, HPMC-E5, and PVP K25) was investigated.
  
  
  RESULTS
  Supersaturation in human gastric fluids was observed for all model compounds, but proved to be relatively unstable (fast precipitation), except for itraconazole. Only modest excipient-mediated stabilizing effects on supersaturation were observed using HPMC-E5 and Eudragit® E PO whereas PVP K25 exerted no effect. In contrast to SGF, the observed precipitation behavior in FaSSGF was similar to the behavior in human gastric fluids.
  
  
  CONCLUSIONS
  The present study demonstrates that supersaturation stability of drugs in human gastric fluids is in general inferior to supersaturation stability in intestinal fluids. As the potential for excipient mediated precipitation inhibition in gastric fluids was only limited, our data suggest that supersaturation should preferably be targeted to the intestine.
authors.affiliation: Laboratory for Pharmacotechnology and Biopharmacy, KU Leuven, Herestraat 49, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Bevernage
authors.forename: Bart
authors.initials: B
authors.lastname: Hens
authors.forename: Joachim
authors.initials: J
authors.lastname: Brouwers
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
mesh_terms: D000328:Adult; D011232:Chemical Precipitation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005260:Female; D005750:Gastric Juice / Q000378:metabolism*; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D055815:Young Adult
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers; D011109:Polymethacrylic Acids; D012997:Solvents; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C518398:Eudragit E PO; D011205:Povidone