Manipulation of corticosteroid release from a transiently supersaturated topical metered dose aerosol using a residual miscible co-solvent.
OBJECTIVE
The creation of supersaturation transiently after application overcomes the issue of drug instability. However, if the solvents used to drive supersaturation evaporate too quickly, drug recrystallisation or rapid film drying can occur which will inhibit drug release. As such the effects of a residual solvent, poly(ethylene glycol) 400 (PEG), on the release, mobility and supersaturation kinetics of a transiently supersaturated formulation were studied.


METHODS
Metered dose aerosol (MDA) formulations consisting of hydrofluoroalkane 134a, ethanol, poly(vinyl pyrrolidone) K90, beclomethasone dipropionate (BDP), and 0%, 5% or 10% w/w PEG were prepared in canisters sealed with metered dose valves and tested for release and adhesion over time.


RESULTS
The addition of 10% PEG to the MDA formulation resulted in a significant reduction (p < 0.05) in steady state drug release rate (230.4 +/- 17.3 microg/cm(2)/h for 0% PEG MDA, 83.6 +/- 4.9 microg/cm(2)/h for 10% PEG MDA). The presence of PEG caused a delay in dose depletion (2 h for 0% PEG MDA versus 4 h for 10% PEG), retarded supersaturation kinetics and increased film drying time.


CONCLUSIONS
Whilst equivalent amounts of BDP were released, the residual solvent altered the drug release profile to achieve more constant delivery.
Reid
Monica L
ML
Pharmaceutical Science Research Division, King's College London, 150 Stamford St, London SE1 9NH, UK.
Brown
Marc B
MB
Jones
Stuart A
SA
D000336:Aerosols; D001507:Beclomethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D036501:Metered Dose Inhalers; D011092:Polyethylene Glycols / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D005466:Fluorocarbons
D000336:Aerosols; D001507:Beclomethasone; D000431:Ethanol; D006845:Hydrocarbons, Fluorinated; D011092:Polyethylene Glycols; D011205:Povidone; C065857:beclomethasone 17-monopropionate; C094049:apaflurane; D005466:Fluorocarbons