Vilazodone Hydrochloride Multi-dose Nasal Spray Solution for the Treatment of Depression: Design, Optimization and Evaluation

Abstract

Introduction: The aim of the present research work was to prepare, optimize, and evaluate the multi-dose nasal spray solution to deliver vilazodone hydrochloride to the brain through the intranasal route in order to overcome the drawback associated with the oral route for the treatment of depression. Background: Depression is a mental disorder associated with abnormalities in neuronal transport in the brain, primarily concerning serotonin, norepinephrine, and dopamine that adversely affect a person's lifestyle, sleep pattern, work, eating habits, and general health. Vilazodone hydrochloride acts by enhancing the serotonergic activity in the brain by inhibiting serotonin (5-HT) reuptake. Methods: The excipients used to formulate vilazodone hydrochloride multi-dose nasal spray solution were sulphobutylether-β-cyclodextrin sodium (solubilizer), sodium carboxymethylcellulose (viscosity builder), tween 80 (surface tension modifier), glycerol (humectant), benzalkonium chloride (preservative), and purified water (vehicle). The simple conventional mixing technique was used for the preparation of the multi-dose nasal spray solution. The solution was prepared in two parts, in the first part sulphobutylether-β-cyclodextrin sodium and drug substance dissolved in purified water under stirring followed by the addition of glycerol and benzalkonium chloride solution. In the second part, tween 80 was dissolved in warm water followed by the addition of sodium carboxymethylcellulose under stirring, finally both parts were mixed together and the required volume was adjusted with purified water. The central composite design was used for the optimization of the formulation. The solution was evaluated for physicochemical properties, selective toxicity, and experimental kinetics. Results: The prepared vilazodone hydrochloride multi-dose nasal spray solution showed viscosity (40.5 ± 1.65 mPa.s), droplet size distribution (span) (1.88 ± 0.55 μm), spray area (288 ± 1.25 mm2), ovality (1.10 ± 1.35), dripping speed (0.25 cm /30 sec), visual appearance (clear free from particulate matter), pH (6.35 ± 0.10), shot weight (100.6 ± 0.32 mg), density (1.03 ± 0.20 g/ml), % drug content (101.8 ± 0.15 %), displacement value for in-vitro mucoadhesion (3.47 ± 0.25 cm), average flux (Jss) for permeability (241.06 ± 1.45 μg/cm2/hrs), permeability coefficient (48.21 ±1.46 cm/hrs), enhancement ratio (1.73), local toxicity study shows no epithelium cell damage, isotonicity (386.58 mOsmol / kg). Plasma Cmax (24.56 ±3.98 ng/ml), Tmax (1.0 hrs), and AUC 0-12 (82.68 ±10.22 ng.h/ml). Brian tissue Cmax (22.95 ±4.22), Tmax (1.0 hrs) and AUC 0-12 (77.82 ±6.25 ng.h/ml). Nasal bioavailability (251.74 ±45.12% ) and, drug targeting index 1.54. Conclusion: The present research work results showed that the prepared multi-dose nasal spray solution of vilazodone hydrochloride was suitable for the delivery of the drug to the brain by the intranasal route which might be beneficial to overcome drawbacks associated with the oral route of administration for the treatment of depression.