Flufenamic acid is a problem drug that has up to eight different polymorphs and shows poor solubility. It belongs to the fenamates subclass of NSAIDs. Traditional uses of fenamates include analgesic treatment of rheumatoid arthritis, migraine, and, especially, primary dysmenorrhea. Fenamates, including flufenamic acid, not only relieve pain associated with dysmenorrhea, but also significantly reduce menorrhagia and craving for other analgesics during the treatment. It should, however, be noted that flufenamic acid shows high inter-individual variability of pharmacokinetic parameters in humans, which has been cited as one of the main limiting factors for its clinical use. Although fenamates exhibit high absorption rates (up to 80%) following oral administration, variable bioavailability was reported for flufenamic acid with peak plasma concentrations ranging between 6 and 20 μg/mL, which were reached between 1.5 and 5 h. Concomitant food intake with flufenamic acid was reported to affect the drug uptake, varying by up to 30% depending on the formulation. Furthermore, highly variable bioavailability was reported for 5 different formulations in vivo highlighting flufenamic acid's reputation as a problem drug.
Our solution: Our data, including solid-state characterizations (XRD, DSC, FTIR) and in vitro drug release in biorelevant media (SGF, FaSIF and FeSIF), show that we can achieve more rapid dissolution from dry powder formulations compared to conventional form. Formulation of flufenamic acid with our platform shows significantly reduced variability in drug release in the fasted/fed simulated intestinal fluid media.