Sustained release pharmaceutical compositions

1. A controlled release oral dosage formulation comprising aplindore, or a pharmaceutically acceptable salt thereof; and

one or more release-rate controlling polymers or release-retarding materials;

wherein the controlled release oral dosage formulation comprises one or more of the following:

a wax matrix wherein the wax is present in an amount by weight of from about 10% to about 60% of the formulation;

a polyethylene oxide matrix wherein the polyethylene oxide is present in an amount by weight of from about 5% to about 40% of the formulation; or a hydroxypropyl methylcellulose matrix wherein the hydroxypropyl methylcellulose is present in an amount by weight of from about 15% to about 80% of the formulation and the hydroxypropyl methylcellulose comprises one high viscosity hydroxypropyl methyl cellulose and one low viscosity hydroxypropyl methyl cellulose;

wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate effective to provide a C max that is about 4,000 pg/mL to about 14,000 pg/mL; and wherein the aplindore, or the pharmaceutically acceptable salt thereof of the controlled release oral dosage formulation, is released at a rate to provide an AUC 0-12 of about 36,000 pg*h/mL to about 109,000 pg*h/mL; and

wherein the controlled release oral dosage formulation comprises a tablet, an encapsulated dosage form, one or more microparticles, or powder, or a combination thereof.

2. The controlled release oral dosage formulation of claim 1 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate effective to provide a C max that is less than about 0.60 times a C max of an instant release formulation.

3. The controlled release oral dosage formulation of claim 1 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate effective to provide a C max that is less than about 0.50 times a C max of an instant release formulation.

4. The controlled release oral dosage formulation of claim 1 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate effective to provide a C max that is less than about 0.40 times a C max of an instant release formulation.

5. The controlled release oral dosage formulation of claim 1 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate to provide an AUC 0-12 of at least about 1.05 times that of the instant release formulation.

6. The controlled release oral dosage formulation of claim 1 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate to provide an AUC 0-12 of at least about 1.1 times that of the instant release formulation.

7. The controlled release oral dosage formulation of claim 1 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate to provide an AUC 0-12 of at least about 1.2 times that of the instant release formulation.

8. The controlled release oral dosage formulation of claim 1 , wherein:

said tablet is a co-compressed tablet or a matrix tablet; said encapsulated dosage form is a capsule; and

at least one of said one or more microparticles is in the form of a pellet, a bead, or a spheroid, or a combination thereof.

9. The controlled release oral dosage formulation of claim 8 , wherein said tablet is a matrix tablet.

10. A method of treating a disorder of the dopaminergic system comprising administering to a patient in need of such treatment an effective amount of a controlled release oral dosage formulation according to claim 1 .

11. The controlled release oral dosage formulation of claim 1 , wherein the controlled release oral dosage formulation comprises a wax matrix wherein the wax is present in an amount by weight of from about 10% to about 60% of the formulation.

12. The controlled release oral dosage formulation of claim 1 , wherein the controlled release oral dosage formulation comprises a polyethylene oxide matrix wherein the polyethylene oxide is present in an amount by weight of from about 5% to about 40% of the formulation.

13. The controlled release oral dosage formulation of claim 1 , wherein the controlled release oral dosage formulation comprises a hydroxypropyl methylcellulose matrix wherein:

the hydroxypropyl methylcellulose is present in an amount by weight of from about 15% to about 80% of the formulation; and

the hydroxypropyl methylcellulose comprises one high viscosity hydroxypropyl methyl cellulose and one low viscosity hydroxypropyl methyl cellulose.

14. A controlled release oral dosage formulation comprising aplindore, or a pharmaceutically acceptable salt thereof;

wherein the aplindore, or the pharmaceutically acceptable salt thereof of the controlled release oral dosage formulation, is released at a rate effective to provide a C max of about 4,000 pg/mL to about 14,000 pg/mL; and wherein the aplindore, or the pharmaceutically acceptable salt thereof of the controlled release oral dosage formulation is released at a rate to provide an AUC 0-12 of about 36,000 pg*h/mL to about 109,000 pg*h/mL; and

wherein the controlled release oral dosage formulation comprises a microparticle wherein the microparticle comprises an inert core; a layer comprising the aplindore or the pharmaceutically acceptable salt thereof disposed on the inert core; and a coating comprising at least one release rate controlling polymer disposed on the layer of the compound.

15. The controlled release oral dosage formulation of claim 14 , wherein the controlled release oral dosage formulation comprises a microparticle wherein the microparticle comprises an inert core; a layer comprising the aplindore or the pharmaceutically acceptable salt thereof disposed on the inert core; and a coating comprising at least one release rate controlling polymer disposed on the layer of the compound; and wherein the at least one release rate controlling polymer of the coating is selected from: Eudragit RS, Eudragit RL, Surelease, and combinations of two or more thereof.

16. The controlled release oral dosage formulation of claim 14 , wherein the controlled release oral dosage formulation comprises a microparticle, wherein the microparticle comprises the inert core; the layer comprising the aplindore or the pharmaceutically acceptable salt thereof disposed on the inert core; and the coating comprising at least one release rate controlling polymer disposed on the layer of the compound; wherein the at least one release rate controlling polymer of the layer comprising aplindore is a hydroxypropyl methyl cellulose; and wherein the at least one release rate controlling polymer of the coating is selected from: Eudragit RS, Eudragit RL, Surelease, and combinations of two or more thereof.

17. The controlled release oral dosage formulation of claim 14 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate effective to provide a C max that is less than about 0.60 times a C max of an instant release formulation.

18. The controlled release oral dosage formulation of claim 14 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate effective to provide a C max that is less than about 0.50 times a C max of an instant release formulation.

19. The controlled release oral dosage formulation of claim 14 , wherein the aplindore, or the pharmaceutically acceptable salt thereof, is released at a rate effective to provide a C max that is less than about 0.40 times a C max of an instant release formulation.

20. The controlled release oral dosage formulation of claim 14 , wherein the pharmaceutically acceptable salt is aplindore fumarate.

21. A method of treating a disorder of the dopaminergic system comprising administering to a patient in need of such treatment an effective amount of a controlled release oral dosage formulation according to claim 14 .