The delayed dissolution of paracetamol products in the canine fed stomach can be predicted in vitro but it does not affect the onset of plasma levels

Int J Pharm. 2005 May 30;296(1-2):87-93. doi: 10.1016/j.ijpharm.2005.02.028. Epub 2005 Apr 7.

Abstract

Although it is generally believed that paracetamol can be used as a marker of gastric emptying, there have been reports in the literature that show delayed dissolution of immediate release paracetamol tablets using standard in vitro setups and food-simulating media, delayed disintegration of paracetamol products in the fed stomach, and no correlation of paracetamol absorption with gastric emptying in the fed state. In this study, we confirmed that dissolution of Panodil and Apotel tablets is delayed in food-simulating media regardless of the in vitro hydrodynamics and on a formulation dependent manner. Further, we assessed the usefulness of in vitro dissolution data in the prediction of delayed disintegration time in the fed stomach and we examined the importance of delayed gastric disintegration on the onset of plasma levels using the canine model. In vitro dissolution data in cow's milk reflected the delayed disintegration of Panodil tablets in the fed stomach. In vitro dissolution of Apotel tablets in milk was delayed less than of Panodil and the effect of dosing conditions on the in vivo disintegration was not apparent. However, for the products tested in this study, there was no correlation between intragastric disintegration and onset of plasma levels probably because gastric emptying in also delayed in the fed state.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / blood*
  • Animals
  • Dogs
  • Fasting / metabolism
  • Food-Drug Interactions / physiology*
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology*
  • Gastrointestinal Contents* / drug effects
  • Male
  • Milk / metabolism*
  • Predictive Value of Tests
  • Solubility
  • Time Factors

Substances

  • Acetaminophen