Xyloglucan Based Nasal in situ Gel Formulation of Mirtazapine for Treatment of Depression

Objectives: The objective of the present work was formulation of thermosensitive mucoadhesive in situ nasal gel of Mirtazapine for depression. The nasal route would overcome the first-pass effect and would enhance its efficacy. Methods: The thermally triggered in situ nasal gel was prepared by cold method using Poloxamer 407 and Xyloglucan. Formulation batches of in situ gel were prepared by using 32 full factorial design. The in situ gel was evaluated for gelling temperature, % drug content, ex vivo permeation study and pharmacodynamic study. Results: The differential scanning calorimetry (DSC) and Fourier Transform Infrared (FTIR) spectroscopy of drug and physical mixture showed compatibility. Drug content and gelling temperature of optimized batch was found to be 85.22-95.92 % and 30-35°C respectively. Ex vivo permeation of optimized formulation F4 was found to be 91.89%. Pharmacodynamic study was performed using despair forced swim test and locomotor activity on mice and it was found that in situ nasal gel of Mirtazapine was more effective than that of the marketed formulation. Stability studies revealed that the optimized formulation was stable. Conclusion: The prepared in situ nasal gel of Mirtazapine enhanced the residence time in the nostrils and enhanced the therapeutic efficacy by avoidance of first-pass metabolism. Key words: In situ nasal gel, Poloxamer 407, Xyloglucan, Mirtazapine, Mucoadhesive, Depression, Gelling temperature. Key message: The novel formulation of Mirtazapine in situ nasal gel containing Xyloglucan possess high mucoadhesive strength for increasing the nasal residence time required for therapeutic effect. It has sufficient viscosity to be poured as nasal drop and then get gelled at nasal physiological temperature.