Formulation, Optimization and Evaluation of Self Emulsifying Immediate Release Tablet of Nebivolol HCl using 32 Factorial Design

Abstract

Nebivolol Hydrochloride (NEB) is a lipophilic molecule with low solubility in GI fluid, and high metabolism which leads to its low oral bioavailability 12%. The aim of the present investigation was to develop immediate release self emulsifying tablet (IR-SET) as solid SMEDDS to enhance the solubility and permeability of the drug. Solubility study, pseudo-ternary phase diagrams and 3 2 factorial design were used to select the components of the system and optimize the composition of liquid SMEDDS. Optimal L-SMEDDS contains Kollisolv GTA, Tween 80 and Propylene glycol as oil, surfactant and co-surfactant, respectively in the ratio of 20:26.66:53.34 % w/w, formulates L-SMEDDS with droplet size (55.98 nm), PDI (0.37), emulsification time (16±1.52 sec) and drug content (97.43±0.30 %).  The liquid SMEDDS were adsorbed onto Neusilin US2 by adsorbtion technique to form S-SMEDDS. DSC and SEM studies suggested that NEB in the S-SMEDDS may be present in the molecular dispersed state and was sufficiently adsorbed onto solid carrier, respectively. S-SMEDDS was compressed into IR-SET by direct compression method and composition of IR-SET was optimized using 3 2 factorial design. Optimal IR-SET showed disintegration time (92 + 0.57 sec), droplet size (68.57 nm), PDI (0.34) and drug content (96.33±0.15 %). In vitro dissolution studies and ex vivo diffusion studies in rat stomach suggested that SMEDDS played an important role in solubility and permeability enhancing effect. Accelerated stability studies indicated that formulation were stable. Our results illustrated the increase in solubility and permeability of drug from IR-SET.