IBUPROFEN

There is huge unmet clinical need to reduce the incidence of abuse/overuse of NSAIDs, which results in 100,000s hospitalisations and 10,000s of deaths annually. For this reason, FDA and EMA demand that NSAIDs are used only for prescribed indication, in the lowest dose and for the shortest duration of treatment. Interpersonal pharmacogenetic variability, variability due to food or water intake, and variability due to formulation have all been recorded for NSAIDs over years. There is need to reduce dose, minimise adverse effects, and enhance onset of action since NSAIDs are the most commonly used drugs on each day and will continue to be used in the future. Ibuprofen is an OTC NSAIDs with probably the lowest incidence of adverse reactions. The solubility of ibuprofen is pH-dependent is the lowest in stomach. Thus, for conventional ibuprofen tablets it takes 1.5-3 hours before peak plasma concentration is achieved, which increases the risk for overdose, since patient is inclined to take another pill. High doses are undesirable because they increase the risk of adverse effects and result in deviation of dose response linearity curve. To enhance the solubility of ibuprofen in stomach and in order to achieve rapid onset, it is formulated in the form of soft liquid gel capsules or salt drug conjugates with lysine or arginine. Soft gel capsules are more expensive than conventional directly compressed tablets. Furthermore, gelatine used for production of soft gel capsules could be undesirable in certain populations for religious or vegetarian reasons. For drug conjugate formulations, e.g. ibuprofen argininate or lysinate, large stoichiometric quantities of aminoacid are needed, which may make the tablets bulky and difficult to swallow. Furthermore, it increases the costs making the tablets.

Our solution: Our data including solid-state characterisations, in vitro drug release in biorelevant media (SGF, FaSIF and FeSIF), and in vivo studies in rats show that we achieve faster dissolution and higher solubility for free acid drug form than normally. The latter results in rapid onset of action and enhanced bioavailability. The trend is consistently observed not only in ibuprofen but also in other profess, i.e. naproxen, flurbiprofen, ketoprofen, or NSAIDs from other subclasses. The beneficial effect of our formulation was verified in side-by-side in vitro drug release studies with state-of-the-art commercial oral dosage forms, including film-coated tablets, soft gel capsules, and lysinate conjugate of ibuprofen.