Drug release from non-aqueous suspensions. II. The release of methylxanthines from paraffin suspensions

Abstract

The release of 3 methylxanthines, i.e. caffeine, theobromine and theophylline, from suspensions in liquid paraffin to an aqueous phase was determined in an in vitro apparatus. The release rates were determined as a function of the pH of the aqueous phase. It was proved that the release process was natural convection-regulated. The release rate per unit area was correlated to the solubility of the drug to the power 1.11. In case of the release of theophylline anhydrate from the suspensions a cake of theophylline hydrate was formed at the interface paraffin/buffer, which resulted in a decreasing release rate. The formation of the cake was mostly completed within 20 min, whereafter the release rate was exactly the same as the release rate of theophylline hydrate.