INFLUENCE OF DIFFERENT VARIABLES ON THE IN-VITRO DISSOLUTION OF A SUSTAINED-RELEASE THEOPHYLLINE DOSAGE FORM

In vitro dissolution studies are valuable tools to judge quality and s tability of sustained release dosage forms and are often utilised to p redict the in vivo performance. For this reason, in vitro dissolution experiments with varying pH, osmolarity, rotation speed, and with addi tion of surfactants were performed with a sustained release theophylli ne (CAS 58-55-9) dosage form (Bronchoretard(R)). In order to mimic the physiological situation of the gastrointestinal tract more closely, t he pH of the dissolution media was changed and human bile was added at different time points. The results obtained show that the in vitro di ssolution of the dosage form differs only slightly for the parameters pH, osmolarity and stirring speed and always lies within in vivo verif ied dissolution limits. However, the addition of sodium dodecyl sulpha te to the dissolution medium markedly altered the dissolution rate whe reas addition of the physiologically surface active human bile did not change the dissolution rate. A comparison with in vivo results indica ted, that only the physiologically adapted model guarantees reliable r esults whereas the addition of synthetic surfactants cannot allow for the prediction of bile or food effects. The meaning of in vitro dissol ution 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.