Influence of suspension stabilisers on the delivery of protein-loaded porous poly (DL-lactide-co-glycolide) (PLGA) microparticles via pressurised metered dose inhaler (pMDI).

This work investigates the feasibility of delivering large (≈ 25 μm) porous poly (lactide-co-glycolide) (PLGA) microparticles containing a model protein via pressurised metered dose inhaler (pMDI). Porous PLGA microparticles were prepared by modified double emulsion method as pMDI suspension based systems containing suspension stabilisers in 1,1,1,2,3,3,3-heptafluoropropane (HFA 227). Physical suspension stability was assessed by visual and optical suspension techniques. Aerosolisation characteristics were investigated using aerosol particle sizing, dose delivery through the valve (DTV) and shot weight. An optimum concentration of suspensions stabiliser was required to achieve physical pMDI suspension stability; values of; 0.0075%w/w PVP K30 or 0.075%w/w PEG 300 were required. Formulations that exhibited good physical stability also showed optimum aerosolisation characteristics. When employing 0.0075% PVP K30 DTV at the start and end of can life was 98.11(±10.01) % and 75.06 (±7.01) % respectively verses values of 37.39 (±11.12) % and 5.57 (±1.72) % without the inclusion of PVP K30. Porous PLGA microparticles show potential as macromolecule/protein carrier and also to target lower regions of the lungs when prepared as pMDI suspension formulations in HFA 227 using suspension stabilisers to achieve consistent dose delivery through the life of the pMDI, however, inter-relationship between the device and the formulation need to be considered to achieve suitable respiratory delivery.