Alprazolam formulations
Alprazolam is a drug used to treat anxiety disorders. Disclosed are sustained-release and controlled-release formulations containing alprazolam. The dosage forms may have particular dissolution profiles and plasma concentrations. Preferred dosage forms do not contain hydroxypropyl methylcellulose.
1 . A sustained-release dosage form comprising
alprazolam or a pharmaceutically acceptable salt thereof,
and a release-retarding material, wherein the release-retarding material does not comprise hydroxpropyl methylcellulose.
2 . The dosage form of claim 1 , wherein the release-retarding material is an acrylate polymer, shellae, zein, hydrogenated vegetable oil, hydrogenated castor oil, or a combination comprising one or more of the foregoing release-retarding materials.
3 . (canceled)
4 . The dosage form of claim 1 , exhibiting a dissolution profile such that at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.
5 . The dosage form or claim 4 , wherein the dissolution medium has a pH of about 6.8.
6 . The dosage form of claim 5 , wherein dissolution is measured by a disintegration test of the Japanese Pharmacopoeia Volume 14, 2001, Pages 31-33, performed in a second fluid.
7 . The dosage form of claim 1 , exhibiting a dissolution profile such that at 9 hours after combining the dosage form with a dissolution medium, greater than 75 wt % and less than 95 wt % or the alprazolam or the pharmaceutically acceptable salt thereof is released.
8 . The dosage form of claim 7 , wherein the dissolution medium has a pH of about 6.8.
9 . (canceled)
10 . The dosage form of claim 1 , exhibiting a dissolution profile such that
at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released;
at 4.5 hours after combining the dosage form with the dissolution medium, greater than 25 wt % to less than 50 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released; and
at 9 hours after combining the dosage form with the dissolution medium, less than 75 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.
11 . The dosage form of claim 10 , wherein the dissolution medium has a pH of about 6.8.
12 . (canceled)
13 . The dosage form of claim 1 , exhibiting a dissolution profile such that
at 2 hours after combining the dosage form with a dissolution medium, greater than 25 wt %, of the alprazolam or the pharmaceutically acceptable salt thereof is released;
at 4.5 hours after combining the dosage form with the dissolution medium, greater than 50 wt % to loss than 75 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released; and
at 9 hours after combining the dosage form with the dissolution medium, greater than 75 wt % to less than 95 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.
14 . The dosage form of claim 13 , wherein the dissolution medium has a pH of about 6.8.
15 . The dosage form of claim 13 , wherein dissolution is measured by a disintegration test of the Japanese Pharmacopoeia Volume 14, 2001, Pages 31-33, performed in a second fluid.
16 . A dosage form comprising alprazolam or a pharmaceutically acceptable salt thereof, and a release-retarding material, exhibiting a dissolution profile such that at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.
17 . The dosage form of claim 16 , wherein the release-retarding material does not comprise hydroxypropyl methylcellulose.
18 . The dosage form of claim 16 , exhibiting a dissolution profile such that
at 2 hours after combining the dosage form with a dissolution medium, less than 25 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released;
at 4.5 hours after combining the dosage form with the dissolution medium, greater than 25 wt % to less than 50 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released; and
at 9 hours after combining the dosage form with the dissolution medium, less than 75 wt % of the alprazolam or the pharmaceutically acceptable salt thereof is released.
19 . The dosage form of claim 16 , wherein the dissolution medium has a pH of about 6.8.
20 . The dosage form of claim 16 , wherein the dissolution is measured by a disintegration test of the Japanese Pharmacopocia Volume 14, 2001, Pages 31-33, performed in a second fluid.
21 - 25 . (canceled)
26 . An oral dosage form comprising alprazolam or a pharmaceutically acceptable salt thereof in controlled-release form which provides a maximum alprazolam plasma concentration (C max ) and an alprazolam plasma concentration at about 24 hours after administration (C 24 ), wherein a ratio of C max to C 24 is less than about 4:1.
27 . The oral dosage form of claim 26 , wherein the ratio of C max to C 24 is achieved at steady-state.
28 . The oral dosage form of claim 26 , wherein the ratio of C max to C 24 is less than about 2:1.
29 - 44 . (canceled)