Background and ObjectiveKetorolac tromethamine (KT), a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase inhibitor, is commonly used for the management of moderate to severe pain. The objective of this study was to compare the pharmacokinetic characteristics of KT in beagle dogs following oral administration of conventional tablets and a novel tablet-in-tablet (TIT) formulation.MethodsA comparative dissolution study was conducted to evaluate the release profiles of both formulations. Non-compartmental analysis was used to determine the pharmacokinetic parameters of each formulation.ResultsApproximately 20% of the administered KT from the TIT formulation was released within the first 30 min, with a cumulative release exceeding 90% at 16 h. In contrast, the conventional tablets released about 50% of the drug within 30 min and completed the release at 4 h. In the single-dose study, the time to reach maximum plasma concentration (Tmax) for conventional tablets was 1 h, while Tmax for the TIT formulation was 5 h. Both maximum concentration (Cmax) and area under the concentration-time curve (AUC) for the TIT formulation were lower than those for conventional tablets. In the repeated-dose study, when equivalent doses (35 mg) of conventional tablets were administered in divided daily doses, the TIT formulation showed no significant differences in most steady-state pharmacokinetic parameters, except for Tmax,ss.ConclusionThe results of this study suggest that the development of a novel KT tablet formulation utilizing the push-pull osmotic pump (PPOP) and tablet-in-tablet techniques warrants further investigation in clinical trials.