Abstract

Purpose: The aim of this research was to develop in situ gelling, bioadhesive nasal inserts of tramadol hydrochloride. Methods: Nasal inserts were prepared by lyophilization of polymer gel solutions. A 3² factorial design was used to investigate the combined effect of two independent formulation variables in the preparation of the nasal inserts. The Carbopol 971P: polycarbophil ratio (X₁) and the amount of polyethylene glycol (PEG) 400 (X₂) were selected as independent variables. Nine batches were taken as per experimental design and evaluated for thickness, water uptake, mass loss, bioadhesion potential and drug diffusion across the nasal mucosa. A full model quadratic equation was obtained from multiple regression analysis. A surface plot is also presented to graphically represent the effect of the independent variables on the evaluation parameters. Results: The prepared nasal inserts are a new dosage form having a sponge-like structure. Both formulation variables show a positive effect on the thickness and water uptake of the nasal inserts. When both variables are simultaneously changed, the mass loss response was found to change in a positive way. The bioadhesion potential was significantly dependent on the Carbopol 971P: polycarbophil weight ratio. Diffusion across the nasal mucosa shows a matrix-type profile and the T₅₀% (Time required to release 50% of the drug from inserts) was found to increase as the concentration of polycarbophil increased. Conclusion: This systematic approach to the formulation design helped in investigating the effect of the formulation processing variables.

Keywords:  Nasal drug delivery   Tramadol hydrochloride   Freeze drying   Factorial design   Carbopol 971P