Rapidly dissolving Felodipine nanoparticle strips -Formulation using Design of Experiment and Characterisation

Felodipine (FDP), a dihydropyridine calcium-channel antagonist is used for the treatment of hypertension and angina pectoris. FDP is poorly soluble drug and upon oral administration, it undergoes first pass metabolism, resulting in bioavailability of 15%. The present work was aimed to formulate rapidly dissolving strips containing FDP nanoparticles for transbuccal administration. Such formulations are absorbed through buccal mucosa resulting in increase in oral bioavailability by circumventing first pass metabolism. Nanosuspension was formulated using solvent-antisolvent sonoprecipitation technique. An ordinary 2³ factorial design was applied using Design Expert® 12 software. Formulated nanosuspensions were characterized for particle size, polydispersity index, zeta potential and saturation solubility. Surface morphology was studied using high resolution transmission electron microscopy, atomic force microscopy and field emission scanning electron microscopy. The optimised nanosuspension D1 formulated with PVP-K30 as stabiliser was selected for further incorporation into the film. Central composite design was applied to select film composition with desirable properties. X-ray diffraction studies were performed to assess the solid-state characteristic of the drug in the formulation. Rapidly dissolving strips were evaluated for weight variation, folding endurance, disintegration time, thickness and surface pH. Scanning electron microscopy image of the optimised film revealed almost granular-shaped nanoparticles dispersed in the polymeric network. Drug release kinetics data of optimised film F5 showed 82 ± 0.47% release within 4 min and release pattern was non-fickian diffusion controlled. Stability studies were conducted at 25 ± 2 °C/60 ± 5% RH for 90 days. Collectively, the developed film demonstrated to possess optimum physical and mechanical properties along with rapid drug release and good stability.