Manipulation of Corticosteroid Release from a Transiently Supersaturated Topical Metered Dose Aerosol Using A Residual Miscible Co-Solvent

Purpose 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...

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Bibliographic Details
Published in:	Pharmaceutical research 2008-11, Vol.25 (11), p.2573-2580
Main Authors:	Reid, Monica L., Brown, Marc B., Jones, Stuart A.
Format:	Article
Language:	eng
Subjects:	Aerosols Beclomethasone - administration & dosage Beclomethasone - analogs & derivatives Beclomethasone - chemistry Biochemistry Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Drug delivery systems Ethanol - chemistry General pharmacology Hydrocarbons, Fluorinated - chemistry Medical Law Medical sciences Metered Dose Inhalers Pharmaceutical technology. Pharmaceutical industry Pharmacology Pharmacology. Drug treatments Pharmacology/Toxicology Pharmacy Polyethylene Glycols - chemistry Povidone - chemistry Research Paper Solubility
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Summary:	Purpose 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. Materials and 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 µg/cm 2 /h for 0% PEG MDA, 83.6 ± 4.9 µg/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. Conclusion Whilst equivalent amounts of BDP were released, the residual solvent altered the drug release profile to achieve more constant delivery.
ISSN:	0724-8741 1573-904X