Rapidly absorbed orodispersible tablet containing molecularly dispersed felodipine for management of hypertensive crisis: Development, optimization and in vitro/in vivo studies

A liquisolid orodispersible tablet of felodipine, a BCS Class II drug, was developed to improve drug dissolution and absorption through the buccal mucosa for management of hypertensive crisis. A 24 full-factorial design was applied to optimize felodipine liquisolid systems (FLSs) having acceptable flow properties and possessing enhanced drug dissolution rates. Four formulation variables; The liquid type, X-1 (PG or PEG), drug concentration, X-2 (10% and 20%), type of coat, X-3 (Aerosil (R) and Aeroperl (R)) and excipients ratio, X-4 (10 and 20) were included in the design. The systems were assessed for dissolution and flow properties. Following optimization, the formulation components (X-1, X-2, X-3 and X-4) were PEG, 10%, Aerosil (R) and 20, respectively. The optimized FLS was compressed into felodipine liquisolid orodispersible tablet using Prosolv (R) as carrier material (FLODT-2). The in vitro and in vivo disintegration times of FLODT-2 were 9 and 7 s, respectively. The in vivo pharmacokinetic study using human volunteers showed a significant increase in dissolution and absorption rates of the formulation of FLODT-2 compared to soft gelatin capsules filled with felodipine solution in PEG under the same conditions. Our results proposed that the optimized FLODT formulation could be promising to manage hypertensive crisis.