Title:  Anionic exchange polymer complexes of buspirone

United States Patent:  6,268,368

Assignee:  American Pharmaceuticals International (Cincinnati, OH)

Filed:  March 1, 2000

A controlled release form of buspirone medicament is described. This medicament comprises a buspirone in intimate admixture with an anionic exchange polymer complexing agent. These components form a complex upon the addition of water and thereby permit improved dosing of buspirone to achieve a more targeted therapeutic effect in patients.

DETAILED DESCRIPTION OF THE INVENTION

It has been found that prolonged or sustained release of buspirone, under the conditions encountered in the gastrointestinal tract, may be achieved through an oral dose of medicament in which the buspirone is or becomes bound in situ as a complex with an anionic exchange polymer.

The buspirone employed to form this complex may be in any conventional form. Most commonly, it is provided as an acid addition salt, preferably buspirone hydrochloride, because of the acceptance of that salt for pharmaceutical purposes.

The anionic exchange polymer with which the buspirone is complexed may also vary widely. The selection of an optimum polymer depends upon the form of the buspirone component and may be made in accordance with well known parameters to facilitate complex formation. Especially preferred anionic exchange resins are sodium carboxymethylcellulose and methacrylic acid/ethylacrylate copolymer. Both complex readily with buspirone hydrochloride.

The nature of the ion exchange polymer can also vary widely within the scope of this invention. To facilitate the controlled release of buspirone, it is desirable that the polymer be hydrophilic. Preferably it is also readily dispersable in the aqueous environment of the gastrointestinal tract and therefore has an average molecular weight of less than 500,000.

The buspirone and ion exchange polymer are complexed in conventional manner. Normally, solid powders of these two components, with or without optional additives, are simply admixed. The complex forms upon exposure to water, either in preparing a liquid dosage form or in situ when a solid dosage form comes in contact with the aqueous fluids of the gastrointestinal tract.

The medicament complex of buspirone-ion exchange polymer may be combined with a wide variety of pharmaceutically acceptable components, conventional in the art, to provide a suitable dosage formulation. For example, where the present medicament is provided in solid tablet form, the complex may be combined with conventional dispersant and tableting agents. These include pharmaceutically acceptable dispersants, fillers, flow agents and/or lubricants.

In a preferred embodiment of the present invention, the medicament and complexing agent are additionally combined with a conventional viscosity enhancer or gelling agent. Most desirably, this component is a hydrophilic polymer such as hydroxylmethylcellulose or polyvinyl pyrolidone. Such a gelling agent appears to insulate the buspirone from the in vivo environment of the gastrointestinal tract, facilitating the absorption of the buspirone into the blood stream.

Normally the daily dosage form of this medicament contains less than about 100 mg, desirably between 10 and 60 mg, more desirably between 15 and 40 mg buspirone. The weight ratio of buspirone to anionic exchange polymer may likewise vary widely. Normally, however, this ratio is between 4:1 and 1:6, desirably between 3:1 and 1:4 and more desirably between about 2:1 and 1:4.

The complexes of the present invention substantially prolong the release of buspirone, as compared to conventional in vitro dissolution times for this drug. Such times are measured by means of the USP paddle method at 50 and/or 100 rpm. In accordance with this method, the complexes of this invention have a dissolution time in water which is in excess of 24 hours for about 50 to 75% by weight of buspirone. By way of comparison, dissolution times for commercially available buspirone in un-complexed form normally exceed 80% in 30 minutes, while the form of buspirone in U.S. Pat. No., 5,431,922 is described as a releasing at least 80% of its buspirone in from 6 to 24 hours. These differences emphasize the degree to which release of this drug is extended by the anionic exchange polymer complex of the present invention.

Claim 1 of 15 Claims

What is claimed is:

1. An oral dosage formulation for controlled release of a medicament comprising buspirone or a pharmaceutically acceptable salt thereof in intimate admixture with an anionic exchange polymer complexing agent.

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