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 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, both 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 dispersible tablets for administration as aqueous oral solution. In one embodiment, the act...

AI Technical Summary

Benefits of technology

[0009] According to the present invention, it has now been found that 1-aminocyclohexanes, such as memantine (1-amino-3,5-dimethyladamantane) and neramexane (1-amino-1,3,3,5,5-pentamethylcyclohexane), and their salts, including the hydrochloride, hydrobromide, mesylate salt as well as other pharmaceutically accepted salts, can be formulated into an immediate release dosage form with dose-proportional bioavailability and advantageous stability profiles where dosage forms preferably disintegrate rapidly.

[0018] In another embodiment of the present invention, the dosage forms contain excipients that have improved stability, forming less than 3.0% w / w lactose adduct, preferably less than 2.5% w / w, upon storage for 36 months at room temperature. The present invention discovered the lactose adduct formation, which was not a foreseen adduct formation reaction. One skilled in art will recognize that an adduct, such as a lactose adduct, is formed by a Maillard reaction between the 1-aminocyclohexane analog active ingredient and a lactose excipient.

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.

Images