Development and in-vitro Characterization of Mucoadhesive in situ Nasal Gel of Ondansetron

The nasal route has gained importance in recent decades as a non-invasive drug application route that offers many advantages for the introduction of drugs into systemic circulation. Its major advantage is the rapid absorption of drugs and therefore quick onset of their effect. In addition, it has the advantage of avoiding the hepatic first-pass effect. Thus, nasal drug delivery may be used for either local or systemic effects. Cancer induced nausea and vomiting is one of the major side effects of the cancer chemotherapy. For the treatment of the CINV the use 5HT3 recepter antagonist is the most effective. Ondansetron has a oral bioavailability of 60% due to the first pass metabolism. So our objective was to prepare an in situ nasal gel of the Ondansetron using PF-127 as the thermo reversible polymer. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. We used HPMC E15 and Chitosan as the mucoadhesive polymer to increase the nasal residence time of the formulation. To increase the permeation we used Polyethylene Glycol 400 and Propylene glycol as the permeation enhancer. Further,  a 3-factor, 2-level full factorial design (23) study was carried out to optimize the Ondansetron gel with PF 127 amount (%, X1), permeation enhancers (PEG 400 1%/PPG 1%, X2) and polymers (HPMC E15 1 %/Chitosan 0.5 %, X3) as the prime selected independent variables, which were varied at 2 different levels (low and high). The effect of formulation variables on the response variables were statistically evaluated by using a commercially available software package Design-Expert® version 8.0 (Stat-Ease, Inc.).The formulation Om2 was found to be the best composition formula based on statistical finding, while conformation experiment also proves this result.