Surge Dose Formulations of NSAIDs Provide for Ultra-Rapid and Consistent Drug Absorption in Both the Fasted and Fed State as Predicted by Physiologically Based Biopharmaceutics Modelling.

This paper describes the use of physiologically based biopharmaceutics modelling (PBBM) to predict the effect of food on diclofenac and ibuprofen absorption from ultra-rapid-release Surge Dose tablets. Fasted-state diclofenac pharmacokinetics (PK) were used with published IV data and biorelevant dissolution data for the diclofenac tablets to develop a mechanistic PBBM model which could be used to predict absorption. The resultant model that best fitted the PK data showed that, in vivo, the ultra-rapid-release tablets behaved like a solution with a median time to peak plasma concentration (T) of 20 min. Incorporating a well-established model for gastric emptying in the fed state, the fed T for these tablets was predicted to be 21 min, similar to that seen in fasted subjects. Use of a PBBM model to predict absorption of ibuprofen in the fasted and fed states again showed that ultra-rapid-release tablets produced fast and consistent absorption independent of the presence of food. Predicted mean T values were 31.8 and 35.4 min in the fasted and fed states, respectively. Therefore, even if Surge Dose formulations are taken after food, as frequently recommended for NSAIDs, the speed of absorption and subsequent onset of action should not be impacted.