Use of sulfoalkyl ether cyclodextrin as a preservative

Abstract

A method of preserving formulations is provided. The method includes the step of including a derivatized cyclodextrin in a formulation capable of sustaining microbial growth. One embodiment of the formulation employs a sulfoalkyl ether cyclodextrin as a preservative and optionally as a solubilizing and complexing agent. A suitable cyclodextrin is the CAPTISOL” brand cyclodextrin (sulfobutyl ether R-cyclodextrin). Whether or not the formulation includes a conventional preservative, the formulation will remain preserved for at least a minimum predetermined period. Specific embodiments of the invention include a carrier, a derivatized cyclodextrin and optionally one or more active agents, one or more water activity-reducing agents, and/or one or more complexation-enhancing agents. The derivatized cyclodextrin reduces the water activity of the formulation. A liquid formulation can be lyophilized or otherwise dried to yield a solid formulation that is optionally reconstitutable.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a method of preserving a formulation by including a sufficient amount of derivatized cyclodextrin in the formulation, and also to preserved formulations containing a derivatized cyclodextrin at least as a preservative in the formulation. BACKGROUND OF THE INVENTION [0002] Preservation of formulations generally involves the use of chemical preservatives to maintain or reduce the amount or concentration of microbes in the formulation below a certain value. In the food, cosmetic and pharmaceutical industries, for example, conventional preservatives are included to inhibit the proliferation of or reduce the rate of proliferation of microbes in the respective products. [0003] Many compounds varying dramatically in structure are known to serve as conventional preservatives. Depending upon the intended application / use of a product, a particular preservative is generally preferred. For example, conventional preservatives for foo...

AI Technical Summary

Benefits of technology

[0033] The present invention seeks to overcome the disadvantages present in known formulations. As such, a derivatized cyclodextrin-based, e.g., sulfoalkyl ether cyclodextrin (SAE-CD)-based, preserved formulation is provided. The present formulation can include any known active agent. The formulation is preserved in terms of its ability to resist microbial contamination, i.e., it has a reduced potential for sustain

Problems solved by technology

Some pharmaceutical formulations, especially those formulations comprising a medium that sustains microbial growth, are particularly prone to contamination by microbes.

In particular, albumin-based and lipid-based formulations are particularly prone to contamination by microbes and always require a conventional preservative in order to maintain an acceptable shelf life.

Lipid-based emulsion formulations are typically problematic with regard to microbial growth, not only because the lipid components can readily support the growth, but because 0.22 μm or smaller “sterilizing” filters cannot be used.

When cyclodextrin formulations are administered by injection into the blood stream, the complex rapidly dissociates due to the effects of dilution and non-specific binding of the drug to blood and tissue components.

The underivatized parent cyclodextrins are known to interact with human tissues and extract cholesterol and other membrane components, particularly upon accumulation in the kidney tubule cells, leading to toxic and sometimes fatal renal effects.

However, the HP-β-CD still possesses toxicity t

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