Background: Frovatriptan is a potent anti-migraine agent with unfavourable slow onset of
action, available on the market as film-coated tablets.
Objective: Optimization, by Quality by Designs strategies, of an orally disintegrating tablet (ODT)
formulation of frovatriptan aimed to make its oral administration easier and its dissolution faster than
the commercial tablets, thus improving its effectiveness in migraine management.
Method: A screening D-optimal design was applied to investigate the effects of different levels of kind
and amount of ODT special excipient and disintegrant agents (identified as the critical variables) on
disintegration time (DT) and % drug dissolved at 30 s (%Diss), selected as the responses to optimize.
The best excipients combination, emerged by the screening step, was in-depth investigated by a Response
Results: A design space was defined where every combination of the selected variables fulfilled the
required values for the responses with P ≥ 95%. In particular, the optimized formulation (Pharmaburst®
60% and Na alginate 15%), showed DT = 1.62±0.08 s and %Diss= 9.02±0.47%, with good agreement
between measured and calculated values. Moreover, the developed ODT complied with the USP uniformity
weight and drug content requirements, exhibited proper hardness and low friability, and provided
100 % dissolved drug within 5 min.
Conclusion: A frovatriptan ODT formulation was successfully developed by Quality by Design. It represents
an effective alternative to conventional tablets, allowing easier oral administration (also to paediatric
and geriatric people) and very faster drug dissolution, enhancing patient compliance and facilitating
an earlier treatment of migraine attacks.