Immediate release formulations of 1-aminocyclohexane compounds, memantine and neramexane

Abstract

The present invention relates to an immediate release solid oral dosage form containing 1-aminocyclohexanes, preferably memantine or neramexane, and optionally a pharmaceutically acceptable coating, wherein the active ingredient exhibits dose proportionality and is released at a dissolution rate of more than about 80% within about the first 60 minutes following entry of said form into a use environment. The dosage form is direct compressed and has a hardness within the range of between about 3 and about 40 Kp, exhibits an average Tmax within the range of about 2 to about 8 hours with an active ingredient load within the range of about 2.5 to about 150 mg. The formulation allows for dose-proportional compositions for once daily or b.i.d. dosing, while maintaining a steady average range of Tmax.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 11 / 155,319, filed Jun. 16, 2005, which claims priority under 35 U.S.C. § 119, based on U.S. Provisional Application Ser. No. 60 / 581,244 filed Jun. 17, 2004, and U.S. Provisional Application Ser. No. 60 / 636,899 filed Dec. 16, 2004, all of which are hereby incorporated by reference in their entirety.FIELD OF THE INVENTION [0002] The present invention is directed to pharmaceutical solid, oral dosage forms of compositions of 1-aminocyclohexane compounds which exhibit an immediate release profile, possess advantageous stability profiles and additionally disintegrate rapidly in aqueous solutions. The invention is particularly suitable for solid pharmaceutical dosage forms of 1-aminocyclohexane compounds in which a therapeutically effective amount of the active ingredient is available in the use environment shortly after administration. These compositions can be provided as...

AI Technical Summary

Benefits of technology

"The present invention provides a new formulation for 1-aminocyclohexanes, such as memantine and neramexane, which can be formulated into an immediate release dosage form with dose-proportional bioavailability and advantageous stability profiles. The dosage form disintegrates rapidly and has a Tmax (the time it takes for the active ingredient to reach its maximum concentration in the body) ranging from about 3 to 8 hours after entry into the use environment. The formulation includes 1-aminocyclohexanes, a coating, and optional excipients such as fillers, anti-adherants, stabilizing agents, binders, colorants, disintegrants, glidants, and lubricants. The oral dosage form can be in tablet or aqueous solution of the active ingredient. The invention also provides a new method for reducing the formation of lactose adducts, which is a common impurity in pharmaceutical formulations."

Problems solved by technology

However, casein has an unpleasant taste; it is associated with the undesirable effect of exacerbating some side effects as disclosed in U.S. Pat. No. 6,413,556; and displays instability in varying pH.

However, this patent does not specifically disclose compositions containing memantine or neramexane.

The patent also does not teach how the release rates affect the Tmax (time to maximum plasma concentration) or that this procedure will result in dose-proportional formulations.

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