In-Vitro, Ex-Vivo and In-Vivo Evaluation of Transdermal Delivery of Felodipine

Felodipine, an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential therapeutic transdermal system candidate, mainly due to its low oral bioavailability, short half life and high first-pass metabolism. Hence an attempt was made to develop transdermal therapeutic systems for felodipine using the polymer blend of eudragit RL100 (ERL) and hydroxypropyl methylcellulose (HPMC) by casting method and to study the effect of polymer composition, plasticizer and permeation enhancer on the physico-mechanical and in vitro drug release characteristics of the film. Polyethylene glycol 400 (PEG 400) and span 60 were used as plasticizer and permeation enhancer respectively. Incorporation of HPMC and PEG 400 improved the flexibility, folding endurance and handling properties and in vitro drug release of the films. The patches were also evaluated for ex vivo skin permeation using human cadaver skin. The presence of span 60 produced significant increase in the flux and permeability. The formulation with ERLHPMC ratio 2:3,4% w/w span 60 as permeation enhancer and 7.5% w/w PEG 400 as plasticizer showed the best results which exhibited the cumulative percentage of drug release of 84.96% and the cumulative amount of drug permeation across skin of 4861.4ng/cm² in 24 hrs. In vivo studies of this transdermal system in rabbits demonstrated a four fold enhancement of bioavailability of felodipine relative to oral administration. It may be concluded that the fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bioavailability and thus, they may improve the patient compliance.