[The effect of different variables on the in vitro dissolution of a theophylline sustained-release preparation]

In vitro dissolution studies are valuable tools to judge quality and stability of sustained release dosage forms and are often utilised to predict the in vivo performance. For this reason, in vitro dissolution experiments with varying pH, osmolarity, rotation speed, and with addition of surfactants were performed with a sustained release theophylline (CAS 58-55-9) dosage form (Bronchoretard). In order to mimic the physiological situation of the gastrointestinal tract more closely, the pH of the dissolution media was changed and human bile was added at different time points. The results obtained show that the in vitro dissolution of the dosage form differs only slightly for the parameters pH, osmolarity and stirring speed and always lies within in vivo verified dissolution limits. However, the addition of sodium dodecyl sulphate to the dissolution medium markedly altered the dissolution rate whereas addition of the physiologically surface active human bile did not change the dissolution rate. A comparison with in vivo results indicated, that only the physiologically adapted model guarantees reliable results whereas the addition of synthetic surfactants cannot allow for the prediction of bile or food effects. The meaning of in vitro dissolution tests thus is limited to development studies of dosage forms and to routine quality and stability control testing. For judging the in vivo characteristics in vitro studies have only limited value and have to be verified by pharmacokinetic studies.