Pressurised metered dose inhalers (MDI)

Abstract

The invention relates to the use of pressurised metered dose inhalers (MDIs) having part or all of their internal surfaces consisting of stainless steel, anodised aluminium or lined with an inert organic coating; and to compositions to be delivered with said MDIs.

Description

[0001] The invention relates to the use of pressurised metered dose inhalers (MDIs) having part or all of their internal surfaces consisting of stainless steel, anodised aluminium or lined with an inert organic coating. The invention also relates to compositions to be delivered with said MDIs. [0002] Pressurised metered dose inhalers are well known devices for administering pharmaceutical products to the respiratory tract by inhalation. [0003] Active materials commonly delivered by inhalation include bronchodilators such as β2 agonists and anticholinergics, corticosteroids, anti-leukotrienes, anti-allergics and other materials that may be efficiently administered by inhalation, thus increasing the therapeutic index and reducing side effects of the active material. [0004] MDI uses a propellant to expel droplets containing the pharmaceutical product to the respiratory tract as an aerosol. [0005] For many years the preferred propellants used in aerosols for pharmaceutical use have been...

AI Technical Summary

Benefits of technology

[0003] Active materials commonly delivered by inhalation include bronchodilators such as β2 agonists and anticholinergics, corticosteroids, anti-leukotrienes, anti-allergics and other materials that may be efficiently administered by inhalation, thus increasing the therapeutic index and reducing side effects of the active material.

[0011] Compositions for aerosol administration via MDIs can be solutions or suspensions. Solution compositions offer several advantages: they are convenient to manufacture being completely dissolved in the propellant vehicle and obviate physical stability problems associated with suspension compositions.

[0016] WO 95 / 17195 describes aerosol compositions comprising flunisolide, ethanol and HFA propellants. It is stated in the document that conventional aerosol canisters can be used to contain the composition and that certain containers enhance its chemical and physical stability. It is suggested that the composition can be preferably contained in vials coated with resins such as epoxy resins (e.g. epoxy-phenolic resins and epoxy-urea-formaldehyde resins).

[0018] It has now been found that the chemical stability problems of active ingredients in solution in HFA propellants can be eliminated by storing and delivering said composition employing metered-dose inhalers having part or all of their internal metallic surfaces consisting of stainless steel, anodised aluminium or lined with an inert organic coating.

[0024] The inhalers according to the invention effectively prevent the chemical degradation of the active ingredient.

Problems solved by technology

The widespread use of these formulations is limited by their chemical instability, causing the formation of degradation products.

Said applications do not however address the technical problem of the chemical stability of the active ingredient but they rather concern a different problem, namely that of the adhesion of micronized particles of the suspended active ingredient to the internal surfaces of the inhaler, such as the can walls, valves and sealings.

Surprisingly and contrary to what reported in the prior art with regard to flunisolide, we found a considerable degradation of the tested active ingredients when their formulations were stored in glass containers type III.