Ultrasonically tailored, chemically engineered and "QbD" enabled fabrication of agomelatine nanoemulsion; optimization, characterization, ex-vivo permeation and stability study

Abstract

The objective of present study was to develop a nanoemulsion formulation of agomelatine (BCS class II drug) for the solubility enhancement. Capmul MCM, Tween 80 and PEG-400 were selected as oil, surfactant and co-surfactant respectively. The high energy ultrasonication method was used for the preparation of nanoemulsion. Three-factor three-level central composite design was employed to get the best formulation. The independent variables selected for the optimization were % oil, %S_mix and sonication time (second). Based on the constraints applied to independent and dependent variables, the optimized formulation was selected with 2% oil, 10% S_mix and 45s sonication time. The experimental values for dependent variables such as hydrodynamic diameter (nm), % transmittance and % CDR were found to be 73.72±2.53nm, 98.2±0.42%, 84.71±4.05% respectively. TEM and AFM-assisted morphological characterization of optimized Ago-NE was done and it was found with a spherical shape. The PDI, Zeta potential and the refractive index of optimized Ago-NE were found to be 0.137±0.016, -7.40±0.12mV and 1.423±0.045 respectively. The viscosity, pH and drug content of optimized Ago-NE were found as 25.12±0.67cP, 6.4±0.17 and 97.83±1.03% respectively. The ex-vivo permeation profile of optimized Ago-NE and agomelatine suspension through goat nasal mucosa were compared till 12h and % cumulative drug permeated was found to be 90% and 40% respectively. The higher drug permeation profile of optimized Ago-NE confirmed that the solubility of agomelatine has been improved.

Keywords: Agomelatine; Atomic force microscopy; Central composite design; Nanoemulsion; Pseudo-ternary phase diagram; Ultrasonication.