title: Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities.
abstract: OBJECTIVE
  To characterize human gastric fluid with regard to rheological properties and gastric lipase activity. In addition, traditional physicochemical properties were determined.
  
  
  METHODS
  Fasted HGA were collected from 19 healthy volunteers during a gastroscopic examination. Rheological characterization of the aspirates was conducted on a TA AR-G2 rheometer, using cone and plate geometry. Lipase activity was measured by continuous titration of released free fatty acid from tributyrate. Further, pH, osmolality, buffer capacity, and surface tension were measured and the total protein content and bile salt level were determined using assay kits.
  
  
  RESULTS
  Rheological examination of HGA showed non-Newtonian shear-thinning behavior with predominant elastic behavior in the linear range. The apparent viscosity was measured to be in the range of 1.7-9.3 mPas at a shear rate of 50s(-1). The FaSSGF and HCl pH 1.2 have no shear-thinning properties and showed lower viscosity (1.1 mPas at 50 s(-1)). The observed viscosity of the HGA will decrease the intrinsic dissolution rate of drugs. The activity of the gastric lipase was 7.4 ± 4.0 U/mL (N = 6, n = 3) and 99.0 ± 45.3 U/mL (N = 19, n = 3) at pH 2.8 and 5.4, respectively. pH, surface tension, buffer capacity, bile salt concentration, and osmolality were measured and compared with literature data.
  
  
  CONCLUSIONS
  The rheological behavior and the mean apparent viscosity of HGA are significantly different from that of water and should therefore be considered important during development of gastric simulated media. Further, the activity of the HGL is active even under fasted gastric conditions and might contribute to the digestion and emulsification of lipid-based drug delivery systems in the entire gastrointestinal tract. HGL should therefore be considered in gastric evaluation of lipid-based drug delivery systems.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pernille Barbre
authors.initials: PB
authors.lastname: Pedersen
authors.forename: Peter
authors.initials: P
authors.lastname: Vilmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Bar-Shalom
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.forename: Stefania
authors.initials: S
authors.lastname: Baldursdottir
mesh_terms: D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000737:chemistry; D002021:Buffers; D016503:Drug Delivery Systems; D005215:Fasting; D005260:Female; D005750:Gastric Juice / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D015203:Reproducibility of Results; D012212:Rheology / Q000379:methods*; D012995:Solubility; D013270:Stomach / Q000187:drug effects / Q000502:physiology; D013499:Surface Properties; D013500:Surface Tension; D013997:Time Factors; D014783:Viscosity
chemical_list: D001647:Bile Acids and Salts; D002021:Buffers; D008055:Lipids; D008049:Lipase
keywords: Biological characterization; Fasted state; Human gastric fluid; Lipase activity; Physicochemical characteristics; Rheological characterization; Simulated gastric media