Predicting drug hydrolysis based on moisture uptake in various packaging designs

Eur J Pharm Sci. 2008 Dec 18;35(5):447-56. doi: 10.1016/j.ejps.2008.09.007. Epub 2008 Oct 1.

Abstract

An attempt was made to predict the stability of a moisture sensitive drug product based on the knowledge of the dependence of the degradation rate on tablet moisture. The moisture increase inside a HDPE bottle with the drug formulation was simulated with the sorption-desorption moisture transfer model, which, in turn, allowed an accurate prediction of the drug degradation kinetics. The stability prediction, obtained by computer simulation, was made in a considerably shorter time frame and required little resources compared to a conventional stability study. The prediction was finally upgraded to a stochastic Monte Carlo simulation, which allowed quantitative incorporation of uncertainty, stemming from various sources. The resulting distribution of the outcome of interest (amount of degradation product at expiry) is a comprehensive way of communicating the result along with its uncertainty, superior to single-value results or confidence intervals.

MeSH terms

  • Computer Simulation
  • Drug Packaging*
  • Drug Stability
  • Drug Storage
  • Forecasting
  • Humidity
  • Hydrolysis
  • Kinetics
  • Models, Statistical
  • Permeability
  • Pharmaceutical Preparations / chemistry*
  • Solutions
  • Temperature
  • Thermodynamics
  • Water

Substances

  • Pharmaceutical Preparations
  • Solutions
  • Water