Pullulan and Pluronic F-127 based in situ gel system for intranasal delivery: Development, in vitro and in vivo evaluation

The current work seeks to use Pullulan and Pluronic F-127 (PF-127), a new gel-forming material, for sildenafil citrate (SLC) intranasal delivery. The cold approach was used to develop an SLC-loaded in situ gel based on thermoreversible polymer PF-127 and mucoadhesive polymer Pullulan. In situ gel systems based on Pullulan responds intelligently to environmental stimuli like charge, pH, temperature, light, and redox. To achieve gelation at physiological temperature formulations were modified to have gelation temperatures lower than 34.1°C. Physical appearance and rheological measurements were used to calculate the temperature of gelation. With the addition of increasing quantities of Pullulan, the gelation temperatures fell (from 34.1°C for 8% w/v, 10% w/v, and 12% w/v 0.5% Pullulan). In the goat nasal mucosal membrane, Pullulan concentration increased the mucoadhesive force in terms of detachment stress. The results of drug permeation testing in vitro investigations over the goat nasal mucosa showed that utilizing an in situ gelling formulation with a Pullulan content of 0.5% or higher can greatly boost the effective penetration coefficient. The formulation was shown to be safe for the nasal mucosa after a histological investigation. Conclusively, Pullulan and PF-127 may be appropriate carriers for SLC intranasal administration.