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STABLE PHARMACEUTICAL COMPOSITION OF MEMANTINE AND PROCESS OF PREPARATION THEREOF

IP.com Disclosure Number: IPCOM000168000D
Publication Date: 2008-Feb-27
Document File: 7 page(s) / 61K

Publishing Venue

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Abstract

The technical field of the disclosure relates to stable pharmaceutical compositions of memantine; and processes of preparations thereof.

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STABLE PHARMACEUTICAL COMPOSITION OF MEMANTINE AND PROCESS OF PREPARATION THEREOF

Abstract

The technical field of the disclosure relates to stable pharmaceutical compositions of memantine; and processes of preparations thereof.

            Incompatibility is one of the many factors affecting the stability and, therefore, the shelf life of a composition.  Incompatibility could take place between two or more active ingredients, active ingredient and excipients, or among the excipients.  The interaction may be physical or chemical.  A classic example of chemical interaction known for several years is the interaction of primary amine drugs with lactose, resulting in discoloration, instability and potency loss.  This degradation is pronounced in the presence of water and/or elevated temperature.  This incompatibility is specifically due to Maillard (or “browning”) reaction in which the “glycosidic” hydroxyl group of a reducing sugar such as lactose reacts with primary amine to form an adduct, resulting in the formation of brown pigmented degradates.  This problem can be solved by designing compositions, which avoid water or are free of excipients such as reducing sugars (lactose).

Memantine is chemically 1-amino-3, 5-dimethyl admantane, and is a subject matter of U.S. Patent Nos. 4,122,193 and 4,273,774, which disclose use of memantine in the central nervous system disorders, especially in the treatment of hyperkinesis.  Memantine, thus bearing a primary amine group is susceptible to Maillard reaction, in compositions using lactose or any other reducing sugar as excipients, particularly, in the presence of water.  Therefore, selection of the excipients and the processesing technologies, especially for amine drugs like memantine remains a matter of prerequisite in preformulation studies, so as to provide a stable composition.

U.S. Publication No. 2006/0002999 by Forest Labs, discloses compositions of memantine, prepared by direct compression, using combination of lactose monohydrate and microcrystalline cellulose that showed less than acceptable limits of lactose adduct.  It further discloses compositions, in which lactose is completely replaced with microcrystalline cellulose and silicon dioxide.

There is still a need for stable compositions of memantine comprising excipients which are compatible with memantine, and are free of lactose and microcrystalline cellulose, to provide an alternative to the formulators.

We have now found that a pharmaceutical composition of memantine may be stabilized with a non-reducing sugar and/or a sugar alcohol.

Hence in one general aspect, there is provided a stable composition of memantine, comprising memantine, a non-reducing sugar and/or a sugar alcohol.

In another general aspect, there is provided a stable composition of memantine, wherein the composition is free of lactose and microcrystalline cellulose.

In another general aspec...