Solid dispersions of opioid antagonists

Abstract

Solid dispersions of stable, amorphous opioid antagonists, particularly [[2(S)-[[4(R)- (3 -hydroxyphenyl)-3(R),4-dimethyl-piperidinyl]methyl] - 1 -oxo-3 -phenylpropyl] amino] acetic acid, with improved water solubility and bioavailability are disclosed. Also disclosed are methods of preventing or treating a side effect associated with an opioid. In addition, methods of treating or preventing pain, ileus, and opioid bowel dysfunction are disclosed.

Description

[0001] Cross-references to related applications [0002] This application claims priority to U.S. application 11 / 543,619 filed on October 5, 2006, which claims the benefit of U.S. application 60 / 724,819 filed on October 7, 2005, the entire disclosure of which is incorporated herein as reference. Technical field [0003] The present invention relates to solid dispersions of opioid antagonists. More specifically, the present invention relates to solid dispersions of stable amorphous opioid antagonists (especially alvimopan) with improved water solubility and bioavailability, and their usage. Background technique [0004] [[2(S)-[[4(R)-(3-hydroxyphenyl)-3(R),4-dimethyl-piperidinyl]methyl]-1-oxo-3-phenyl Propyl]amino]acetic acid dihydrate (USAN name is Evimopan) is a mu opioid antagonist that acts in the periphery, and can be used to treat postoperative intestinal obstruction and opioid-induced intestinal dysfunction, and other adaptations disease. Aveimopan is a zwitterionic 3,4-disu...

AI Technical Summary

Problems solved by technology

[0006] [[2(S)-[[4(R)-(3-hydroxyphenyl)-3(R),4-dimethyl-piperidinyl]methyl]-1-oxo-3-phenyl The crystalline dihydrate of propyl]amino]acetic acid (Alvimopan) is more effective than the amorphous [[2(S)-[[4(R)-(3-hydroxyphenyl)-3(R),4-di Methyl-piperidinyl]methyl]-1-oxo-3-phenylpropyl]amino]acetic acid has lower water solubility and is therefore less bioavailable than the amorphous form

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