Controlled Release Muscarinic Receptor Antagonist Formulation

1 . A stable controlled release oral pharmaceutical composition comprising:

(a) a core comprising a therapeutically effective amount of tolterodine and at least one pharmaceutically acceptable excipient;

(b) a rapidly disintegrating or rapidly dissolving coating applied directly to the core; and

(c) a controlled release coating applied to the rapidly disintegrating or rapidly dissolving coating wherein the controlled release coating comprises a water insoluble film forming polymer and a pore forming agent.

2 . The pharmaceutical composition as defined in claim 1 wherein the pharmaceutical composition is a multiparticulate dosage form wherein the dosage form comprises a plurality of particles that comprise elements (a), (b) and (c).

3 . The pharmaceutical composition as defined in claim 1 wherein the tolterodine is a pharmaceutically acceptable salt of tolterodine.

4 . The pharmaceutical composition as defined in claim 1 wherein the tolterodine is tolterodine tartrate.

5 . The pharmaceutical composition as defined in claim 1 wherein the rapidly disintegrating or rapidly dissolving coating exhibits a low water vapor transmission rate as determined by a water permeability analyzer wherein a test sample of the rapidly disintegrating or rapidly dissolving coating is tested for under 25° C./60% relative humidity, 25° C./80% relative humidity and 40° C./75% relative humidity and the slope of the water vapor transmission versus time plot exhibits a slope that is less than 60 under all three test conditions.

6 . The pharmaceutical composition as defined in claim 5 wherein the slope of the water vapor transmission versus time plot exhibits a slope that is less than 40 under all three test conditions.

7 . The pharmaceutical composition as defined in claim 6 wherein the slope of the water vapor transmission versus time plot exhibits a slope that is less than 20 under all three test.

8 . The pharmaceutical composition as defined in claim 1 wherein the core is a core comprising the tolterodine and at least one pharmaceutically acceptable excipient and wherein the core is prepared by extrusion spheronization and does not contain a film forming polymer.

9 . The pharmaceutical composition as defined in claim 1 wherein the controlled release coating further comprises a pH dependent material.

10 . The pharmaceutical composition as defined in claim 9 wherein the controlled release coating further comprises a first controlled release coating comprising a water insoluble polymer and a pore forming agent and a second controlled release coating comprising a pH dependent polymer.

11 . A stable controlled release oral pharmaceutical composition comprising a plurality of particles wherein at least one of the particles consists essentially of:

(a) a core comprising a therapeutically effective amount of tolterodine tartrate and at least one pharmaceutically acceptable excipient;

(b) a rapidly disintegrating or rapidly dissolving coating applied directly to the core that exhibits a low water vapor transmission rate as determined by a water permeability analyzer wherein a test sample of the rapidly disintegrating or rapidly dissolving coating is tested for under 25° C./60% relative humidity, 25° C./80% relative humidity and 40° C./75% relative humidity and the slope of the water vapor transmission versus time plot exhibits a slope that is less than 60 under all three test conditions; and

(c) a controlled release coating applied to the rapidly disintegrating or rapidly dissolving coating wherein the controlled release coating comprises a water insoluble film forming polymer and a pore forming agent.

12 . The pharmaceutical composition as defined in claim 11 wherein the slope of the water vapor transmission versus time plot exhibits a slope that is less than 40 under all three test conditions.

13 . The pharmaceutical composition as defined in claim 11 wherein the slope of the water vapor transmission versus time plot exhibits a slope that is less than 20 under all three test conditions.

14 . The pharmaceutical composition as defined in claim 11 wherein the core is prepared by extrusion spheronization.

15 . The pharmaceutical composition as defined in claim 11 wherein the controlled release coating further comprises a pH dependent material.

16 . The pharmaceutical composition as defined in claim 11 wherein the controlled release coating further comprises a first controlled release coating comprising a water insoluble polymer and a pore forming agent and a second controlled release coating comprising a pH dependent polymer.

17 . A stable controlled release oral pharmaceutical pellet consisting essentially of:

(a) an extruded spheronized core comprising a therapeutically effective amount of tolterodine tartrate, lactose and microcrystalline cellulose;

(b) a rapidly disintegrating or rapidly dissolving coating applied directly to the core that exhibits a low water vapor transmission rate as determined by a water permeability analyzer wherein a test sample of the rapidly disintegrating or rapidly dissolving coating is tested for under 25° C./60% relative humidity, 25° C./80% relative humidity and 40° C./75% relative humidity and the slope of the water vapor transmission versus time plot exhibits a slope that is less than 40 under all three test conditions;

(c) a controlled release coating comprising a water insoluble polymer and a pore forming agent; and

(d) a delayed release coating comprising a pH dependent polymer.

18 . The controlled release pellet as defined in claim 17 wherein the rapidly disintegrating or rapidly dissolving coating comprises polyvinyl alcohol.