Fast Dissolving Oral Thin Film Drug Delivery Systems Consist of Ergotamine Tartrate and Caffeine Anhydrous

Abstract

Ergotamine tartrate (ET), a serotonin 5-HT1 receptor agonist, is an anti-migraine drug. Due to high first-pass metabolism, ET shows a very low bioavailability in oral administrations (<1%). Caffeine (CA) increases the rate and extent of water solubility of ET. The present study intended to investigate the possibility of developing ET fast dissolving thin films for the fast drug dissolution in the oral cavity, and thus bypassing first pass metabolism for providing quick onset of action of the drug. Methods: The films (ET and CA) were prepared according to solvent casting method, separately. Low viscosity grade of hydroxylpropyl methylcellulose (HPMC E-15) was employed in preparation as a film forming polymer. Propylene glycol was the plasticizer used. All the films were evaluated for their thickness, weight variations, folding endurance, surface pH, disintegration, drug content, DSC, in-vitro drug release, and ex-vivo permeation. Results: The best polymer drug ratio in ET/CA films was 1:20 (E2) and 1:4 (C2), respectively. The films E2 and C2 showed 9.9, 3.2 mg weight, 74, 45 µm thickness, 120.66, up to 300 folding endurance and 0.38, 0.52 mg/cm2 drug content, respectively. The DSC showed no stable characteristic for ET and CA in the drug loaded films and revealed amorphous form. The results showed that ET films prepared had faster release and CA films had slower release (p<o.o5). Both films (ET and CA) exhibited good mucoadhesion properties and shorter retention time (36-150 s). Conclusion: The formulations were found to be a suitable candidate for the development of oral thin films for migraine therapy.

Keywords: Mucoadhesive, Oral film, Ergotamine tartrate, Caffeine anhydrous, In vitro studies