Formulation Development and in vitro Evaluation of Montelukast Nasal Sprays / Thunyaporn Jullaphant

Abstract

Montelukast sodium is classified as a leukotriene receptor antagonist. It is used for prophylaxis and treatment of asthma and allergic rhinitis by oral administration. Although, montelukast safety profile is quite similar in adult and pediatric populations; there are some reports that montelukast has a number of the systemic side effects and adverse effects. The systemic side effects of montelukast include cough, fever, bronchitis and adverse effects along with liver dysfunction, agitation, hallucinations, depression, insomnia as well as suicidal ideation. Therefore, local administration of montelukast is expected to reduce the dose and possibly avoid the adverse effects. This study was aimed to develop montelukast nasal spray using either hydroxypropyl cellulose (HPC) or carbomer940 (C940) as mucoadhesive polymers and to characterize the physicochemical properties including in vitro evaluation of the prepared formulations. Eleven designed formulations comprising of one polymer with various concentrations were prepared. The statistical analysis were done using a Student's t- test with GraphPad Prism version 6.00 and significance level (p-value) of <0.05 was considered as statistically significant. The results indicated that the different polymer concentrations were the factors affecting the properties of nasal sprays. The pH of all formulations were in the range of 6.5 - 7.5 and the hydrodynamic particle sizes were between 70 to 300 um. The zeta potential of the formulations containing C940 ranged from -45 to -30 mV whereas for the formulations containing HPC were between -25 to -3 mV. The viscosity of all formulations were in the wide range of 6-320 cP. The contact angle, surface tension, adhesiveness and the droplet size of all formulations were dependent on the concentrations of the polymers. The stability data revealed that only 0.01% w/v C940 was stable when it was stored at 25°C for 3 months. It showed no toxicity to human nasal epithelial cells as well as it did not decrease affect the transepithelial electrical resistance when it was observed before and after exposure to the spray formulation. We conclude that the MTS with 0.01% w/v C940 provided suitable nasal spray formulations.