Background/Objectives: 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. Methods: 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. Results: 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_max) of 20 min. Incorporating a well-established model for gastric emptying in the fed state, the fed T_max 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_max values were 31.8 and 35.4 min in the fasted and fed states, respectively. Conclusions: 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.