Package and device for simultaneously maintaining low moisture and low oxygen levels

Abstract

The present invention relates to a device for reducing the oxygen content of the air surrounding pharmaceutical dosage forms contained within an oxygen-permeable bottle, while also maintaining a relatively low moisture level in said air during the shelf-life of the product. Accordingly, a pharmaceutical package contains a dessicant in a first sub-container and a self-activated oxygen-absorber in a second sub-container.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a device for reducing the oxygen content of the air surrounding pharmaceutical dosage forms contained within an oxygen-permeable bottle, while also maintaining a relatively low moisture level in said air during the shelf-life of the product. BACKGROUND OF THE INVENTION [0002] Oxygen induced drug degradation is a factor that can limit the shelf life, usually as indicated by the expiration date, of a drug product. In the case of drugs that are highly oxygen-sensitive, such degradation may render a drug unmarketable or cause a candidate to be excluded from development. [0003] In some cases, oxygen sensitivity occurs only in the presence of certain excipients. Since oxidation is often not accelerated by standard Arrhenius-based increased temperature studies (known in the art as “accelerated aging studies”), instances can occur in which the oxygen sensitivity of the drug is not recognized until drug development has progressed...

AI Technical Summary

Benefits of technology

[0013] The present invention provides a pharmaceutical package comprising an oxygen permeable bottle containing therein at least one sub-container containing a self-activated oxygen absorber and at least one sub-container containing a desiccant. The sub-containers can be separate units or unitary, i.e., fabricated together as separate compartments within a single unit, termed herein a “cartridge”, containing the self-activated oxygen absorber in one compartment and the desiccan

Problems solved by technology

In the case of drugs that are highly oxygen-sensitive, such degradation may render a drug unmarketable or cause a candidate to be excluded from development.

At such later stages of development, reformulation and addition of standard antioxidants can require considerably more time and money.

European Patent Application Nos. 864630A1 and 964046A1 describe the use of iron iodide and bromide to allow oxygen absorption in a low humidity environment without the need to bring in water; however, commercial application of this technology has not been realized.

In the pharmaceutical industry, there have been some limited reports of using oxygen absorbers to stabilize drugs.

Although these systems perform well for many pharmaceutical applications, they cause the humidity in the bottle environment to be at 55 to 75% relative humidity, since the oxygen consumption reaction requires humidity to operate.

Although it is possible to dry the bottle environment somewhat using a desiccant, the oxygen absorber will, in general, also be dried by the desiccant and be less effective at removing the oxygen permeating through the bottle walls.

The result is that the oxygen level in the bottle will not remain low enough to provide for beneficial stabilization of the pharmaceutically active ingredient over its entire shelf life.

These absorbers, however, provide only a limited absorption capacity (typically less than about 40-cc of oxygen), which is not adequate to provide for protection of pharmaceuticals in permeable packages for a typical shelf life of at least two years.

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