DOE Optimized Self-Nanoemulsifying Drug Delivery System (SNEDDS) Based Cilnidipine Formulations For Bioavailability Augmentation: Physical Characterization And Pharmacodynamic Assessment

Abstract

Background: Cilinidipine (CIL), an antihypertensive agent in the BCS class II category, has poor bioavailability constraints owing to
limited aqueous solubility. Self-nano emulsifying drug delivery system (SNEDDS) provides excellent solubilizing capacity to poorly
water dissolvable drugs since its ternary constituents possess traits like solubilisation/ nanonization activity led by surfactant/cosolvent
and. SNEDDS possesses blends of surfactants and cosolvents to inherit its dispersion behaviour in nanodroplet forms.
Objective: The present investigation aims to develop a DOE-optimized lipid-based system. For enhancement of oral bioavailability of
CIL, Ternary components were screened out for higher CIL solubility, and the purpose of developing ternary phase diagrams was to
feature the regions where nanoemulsion area existed.
Methods: Formulations were designed on the basis of DOE, where data modelling between independent variables (% oil, oil/six ratio
and drug loading) and dependent variables (droplet size, clearity and drug solubility) under Box Behnken design was investigated and
optimized.
Results: Self-nano emulsifying and solubilization capacity were produced from (SNC7) comprised of 40.4% (w/w) Ethyl Oleate as
oil, 48.6% (w/w) Cremophor EL as a surfactant, and 11% (w/w) Transcutol as cosurfactant. The typical drop size and zeta potential of
SNC-7 were 72.10 nm and 1.96±0.045 mv, respectively. DOE optimization showed optimized SNEDDS produced quick dissolution
of CIL over its suspension. It could be attributed to better solubilization potential with enhanced interfacial activity. Pharmacokinetic
data showed optimized system produced 2.5 folds enhancement.
Conclusion: DOE-based SNEDDS design improved the oral bioavailability of CIL with an approach SNEDDS-based formulation of
CIL could be employed for improvised dissolution and oral bioavailability parameters.