Physicochemical stability and aerosolization performance of mannitol-based microcomposites

The aim of this work was to test the stability of mannitol-based co-spray-dried microcomposites containing meloxicam for use as dry powder inhalers. The effects of temperature and relative humidity (RH) on the physicochemical properties and aerosolization performance were investigated and the effects of polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) were analysed. Accelerated stability tests performed at 40 ± 2 °C and 75 ± 5 % RH during 6 months demonstrated that the mannitol-based microcomposites containing meloxicam, PVA and L-leucine were more stable than those containing PVP against RH and temperature. As concerns water uptake, the number of hydrogen-bonds was lower after storage in the case of the samples containing PVP, and the fine particle fraction, which determines the aerosolization parameter, therefore decreased below 50 %. Such a composition may serve as an innovative drug delivery system for local lung treatment in the anti-inflammatory and mono- and combination therapy of cancer, pulmonary fibrosis and pain.