Can Biorelevant Dissolution Testing Help Elucidate Salt Formulation Effects on Plasma Levels and Onset of Action? A Study of Ibuprofen and its Salts

Introduction: Salt formulations are widely used in the pharmaceutical industry to increase drug solubility and accelerate dissolution. In this work, the enhancing effect of salt formulations on the absorption rate of ibuprofen was investigated in both the fasted and fed states, using biorelevant dissolution testing.
Methods: The dissolution behavior of two different ibuprofen salts was studied using two commercially available formulations: Dolormin, containing the lysinate salt of ibuprofen, and Spedifen, containing the arginate salt. Their dissolution was compared to that of the orodispersible tablet formulation containing the free acid (Nurofen) at different dose levels in both single and two-stage dissolution tests.
Results: When administered in the fasted state, the rapid onset of action of the pharmaceutical salt formulations is directly related to their dissolution behavior, highlighting the importance of choosing suitable dissolution media and methodology to link in vitro with in vivo data. In the fed state, gastric emptying becomes rate-limiting to absorption, such that even fast-dissolving products are not able to provide a short onset of action.
Conclusion: Biorelevant dissolution delivers key data for determining pharmaceutical salt formulation effects on dissolution in the fed and fasted states.