Medicinal aerosol formulations

A method for preparing a stabilized medicinal aerosol suspension formulation of micronized formoterol fumarate dihydrate (FFDH) and micronized fluticasone propionate (FP) in a liquid phase comprising an HFA propellant, or pharmaceutically acceptable salts thereof, for MDI administration, the method comprising

• selecting amounts of (a) FFDH and (b) FP to achieve the required therapeutic dose,
• measuring the true particle density of (a), (b) and (c), a moisture-scavenger excipient comprising sodium cromolyn, by a method comprising helium pycnometry,
• determining the density of the liquid phase,
• calculating the required amount of (c) needed to form floccules of (a), (b), and (c) having an average density the same as the density of the liquid phase ±0.2 g/cm3,
• incorporating the selected amounts of (a), (b), and the calculated amount of (c) into the liquid phase, and
• forming floccules of (a), (b), and (c) having a density substantially the same as that of the liquid phase and providing a stabilized medicinal aerosol suspension formulation of FFDH and FP for MDI administration,
• wherein the amounts of (a), (b), and (c), are based on the total weight of the formulation and are selected from within the following ranges
• a) 0.003-0.04%;
• b) 0.01-0.6%;
• c) 0.01-0.1%;
• the HFA propellant is HFA 227,
• and the formulation has stability over a storage period from 3 to 18 months and the water content of the formulation after the storage period is in the range of 500 ppm to 800 ppm.