An in vitro model for exploring CR theophylline-milk fat interactions

Abstract The dissolution of the controlled-release theophylline formulations, Theodur tablet and Theodur sprinkle capsule, was studied in buffer of pH 6.5 and in milk with varying fat contents i.e. 0.1%, 2.0%, 5.0% and 7.5%. The topographical dissolution characterization made was based on a three-dimensional format with independent variables, time and percent fat content of milk. This plot revealed that the dissolution of capsule was markedly lower in all types of milk than in buffer. The dissolution of tablet was higher in milk with 0.1% fat content and slightly higher in milk with 2.0% and 5.0% fat content when compared to that in buffer. The dissolution of tablet in milk with 7.5% fat content was initially lower and then became progressively faster than observed in the aqueous medium. Binding experiments of theophylline to milk with 0.1% and 2.0% fat content, using concentrations encountered during the dissolution process, showed no significant interaction between theophylline and milk. The dissolution data clearly indicate a milk fat content dependent interaction between theophylline formulations and milk. In vivo data reported in literature and observed under “high fat meal” conditions were correlated with the dissolution data. Linear correlations were established in all cases. It was concluded that the 7.5% fat content milk mimics more closely the “high fat meal” conditions. This would aid the development of an appropriate dissolution test capable of simulating non-fasting conditions.