Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Patent
1997-02-07
1999-11-30
Bawa, Raj
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
424 46, A61K 912
Patent
active
059937815
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
This invention relates to improvements in or relating to pharmaceutical compositions comprising a fluticasone ester. In particular the invention relates to novel formulations of use in the administration of fluticasone propionate by inhalation.
BACKGROUND OF INVENTION
Fluticasone propionate is the approved name for S-fluoromethyl 6a, 9a-difluoro-11b-hydroxy-16a-methyl-17a-propionyloxy-3-oxandrosta-1, 4-diene 17b carbothioate, a corticosteroid known to exhibit topical antiinflammatory activity and described and claimed in GB 2088877. In the treatment of asthmatic conditions it has been found to be effective to administer fluticasone propionate in the form of dry powders or aerosols containing small particles of the medicament, conventionally prepared by micronisation. Conventionally, fluticasone propionate aerosols have been administered by means of metered dose inhalers, which are designed to deliver a fixed unit dosage of medicament per actuation or "puff". However, some patients, in particular children and the elderly, have difficulty in coordinating actuation of a metered dose inhaler with inhalation, and are therefore unable to use this mode of administration effectively. Furthermore, a proportion of patients find inhalation of dry powders difficult or unpleasant. There is therefore a demand for a pharmaceutical formulation containing fluticasone propionate in a form suitable for nebulisation.
SUMMARY OF INVENTION
The present invention accordingly provides, in a first aspect, a formulation suitable for nebulisation comprising: less than 12 microns;
Fluticasone propionate may be prepared by methods known in the art, for example, as disclosed in GB 2088877. It will be appreciated that solvates of fluticasone propionate can be prepared and, accordingly, the present invention extends to formulations comprising physiologically acceptable solvates of fluticasone propionate. The particle size of the crystalline material may be reduced by conventional methods, for example, by micronisation, and should be such as to permit inhalation of substantially all the medicament into the lungs upon administration of the nebulised formulation. Suitably the particle size will be in the range of 0.5 to 12 microns, such as 1 to 6 microns.
For introduction of the fluticasone propionate into the lungs, the droplet size of the nebulised formulation is an important parameter. Droplet size depends to some extent on the type of nebuliser used, whether a facemask or a mouthpiece is used and the pressure or flow rate of the compressed gas, as well as on the physical properties of the formulation for nebulisation. The nebulised formulation will be heterodisperse, i.e. droplets will cover a range of sizes. Typically, mean droplet size will be in the range of 0.5 to 15 microns, preferably 0.5 to 10 microns, more preferably less than 5 microns.
The formulation according to the invention desirably contains 0.5 to 10% w/w, preferably 1 to 9% w/w especially 1.5 to 6.5% w/w, of fluticasone propionate relative to the total weight of the solid ingredients of the formulation.
The surfactants used in the formulations of the present invention must be physiologically acceptable upon administration by inhalation. Within this category are included surfactants such as sorbitan trioleate (Span.sup.R 85), sorbitan mono-oleate, sorbitan monolaurate, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan mono-oleate, natural lecithin, oleyl polyoxyethylene (2) ether, stearyl polyoxyethylene (2) ether, lauryl polyoxyethylene (4) ether, block copolymers of oxyethylene and oxypropylene, synthetic lecithin, diethylene glycol dioleate, tetrahydrofurfuryl oleate, ethyl oleate, glyceryl mono-oleate, polyethylene glycol 400 and glyceryl monolaurate.
Particularly preferred surfactants of use in the formulations of the present invention are sorbitan monolaurate and polyoxyethylene (20) sorbitan monolaurate (also known as polysorbate 20).
Suitably the formulations according to the invention contain 0.25 to 0.75% w/w, pre
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Ilott Trevor Leslie
Lam Li Fong
Snell Dorothy Jill
Tainsh David Alexander
Bawa Raj
Glaxo Wellcome Australia Ltd.
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