Formulation development and in-vitro evaluation of montelukast sodium pressurized metered dose inhaler

Abstract

Montelukast is used as alternative treatment for asthma. However, some adverse drug reactions have been reported for the oral dosage form of montelukast. To counter this issue, the drug was formulated into a pressurized metered-dose inhaler (pMDI), which delivered montelukast directly to the lower regions of the lungs. Montelukast sodium, mixed with either HFA 134a propellant or a mixed propellant (HFA-134a and HFA227), was formulated into a pMDI with other excipients. The canister was prepared using a pressurized filling method, followed by disk sampling to assess content per spray and content uniformity. The effects of ethanol and polyethylene glycol (PEG) 400 on the fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of the formulation were evaluated. In vitro cytotoxicity of the developed montelukast pMDIs was tested in lung airway cell lines. Their effects on the levels of inflammatory nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), generated from NR8383 alveolar macrophage (AM) cells, were also evaluated. All selected formulations had a FPF >46%, whereas the formulation containing 20% v/v ethanol and 1% v/v PEG 400 showed the highest FPF. The MMADs of all formulations were within 1–5 μm. The montelukast pMDI formulations were found to be non-toxic to lung airway cell lines and did not induce inflammatory NO, TNF-α, or IL-1β production in NR8383 cells.