Quality by design based silymarin nanoemulsion for enhancement of oral bioavailability

Silymarin has been approved as a safe herbal hepatoprotective drug as well as drug of choice for several hepatic disorders. However it suffers from the problem of poor oral bioavailability. In current work silymarin loaded nanoemulsions were prepared using high pressure homogenization (HPH) technique. Capryol 90, Solutol HS 15 and Transcutol HP were selected as oil phase, surfactant and co-surfactant, respectively. Quality by design was employed to optimize nanoemulsion in terms of amount of surfactant/co-surfactant mixture (Smix), processing pressure and number of cycles. Globule size, polydispersity index (PDI), zeta potential, transmittance and percentage in vitro drug release of optimized formulation were found as 50.02 ± 4.5 nm, 0.45 ± 0.02, −31.49 mV, 100.00 ± 2.21% and 90.00 ± 1.83%, respectively. The everted gut sac studies showed that the nanoemulsion facilitated the improvement of the apparent permeability coefficient (Papp). Papp of silymarin in nanoemulsion and oral suspension was 1.00 × 10−5 cm/h with flux of 0.422 μg/cm2/h and 6.30 × 10−6 cm/h with flux of 0.254 μg/cm2/h at 2 h, respectively. Pharmacokinetic study showed significantly (p < 0.05) enhanced bioavailability of silymarin in nanoemulsion as compared to oral suspension thus nanoemulsion can be a promising oral delivery system for silymarin with enhanced oral bioavailability.

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