ENHANCEMENT OF BIOAVAILABILITY OF POORLY WATER-SOLUBLE DRUG BY SOLID SMEDDS

Lecardipine HCl (LCD) is a highly lipophilic dihydropyridine calcium antagonist indicated for the treatment of mild to moderate hypertension. It has poor aqueous solubility (less than 5 μg/ml) and its oral bioavailability is around 10%. The primary objectives of the present work was to develop, optimize and characterize the composition of a stable liquid and solid self-micro emulsifying drug delivery system (SMEDDS) of LCD HCl and to evaluate its oral bioavailability in rats. The LCD SMEDDS was prepared using Capmul MCM L8 (oil), Cremophor ELP (surfactant), and propylene glycol (cosurfactant). Liquid SMEDDS were converted to solid SMEDDS by adsorbing it on inert solid carrier. Flow properties were determined and solid-state characterization was done by SEM, DSC and XRPD. Optimized formulation showed complete release within 60 min. Stability study was done to check any drug precipitation or instability. HPTLC method was used to interpret in vivo studies of solid SMEDDS in rats. Area under curve and time were compared with those of pure drug suspended in 1% CMC solution. The area under curve and time showed significant improvement as the values obtained were 7680.19 ng h/ml and 1h for SMEDDS in comparison to 3574. 191 ng h/ml and 1.5 h for pure drug suggesting significant increased in oral bioavailability of SMEDDS of LCD HCl.