Formulation and Evaluation of Ion-Activated in Situ Gel of Metoprolol Tartrate for Nasal Administration

Metoprolol tartrate, a selective beta-blocker is completely absorbed from GIT (95%) but is only 40% bioavailable owing to first-pass metabolism. The present investigation has been carried out with the aim of avoiding first-pass metabolism by formulating the drug for nasal administration, based on the concept of ion-activated in situ gelation using gellan gum. In situ gels were formulated using different concentrations of gellan gum. To all the formulations 2.5%w/v of metoprolol tartrate was added, pH adjusted to 4.5 by 0.5 M NaOH solution and terminally sterilized by autoclaving at 121°C and 15 psig for 20 min. Formulations were slightly viscous solutions (1.330-3.130Pa.s) at pH 4.5 and viscosity increased markedly (19.350-48.970Pa.s) in phosphate buffer saline (PBS) of pH 7.4 depending upon concentration of gellan gum. Mucoadhesive force from 23.53±0.58 to 35.73±1.02dynes/cm² was found. In vitro percent drug release after 8hrs from different formulations was from 79.57±0.29-99.05±0.42. Drug release followed Higuchi's diffusion mechanism. On the basis of viscosity, mucoadhesive force and in vitro release, the optimized formulation G4 containing 0.4%w/v of gellan gum was subjected for in vitro permeation studies and histological studies using porcine nasal mucosa. The permeability coefficient of optimized formulation was found to be 1.39x10^-5cm/sec. Histological study shows no change in mucosa as compared to control. All formulations showed good stability with no significant change after exposure to 40°C and 75% relative humidity for 3 months.