Claims for Patent: 12,427,136

Summary for Patent: 12,427,136

Title:	Formulations of apremilast
Abstract:	Provided herein are oral dosage forms comprising a) a core tablet comprising (i) a drug layer comprising apremilast and hypromellose acetate succinate (HPMCAS) in an amorphous solid dispersion; and (ii) a swellable layer comprising one or more swellable polymers; and b) a coating layer disposed on the core tablet, wherein the oral dosage form surface comprises at least one drug release orifice. The disclosed oral dosage forms provide once-a-day dosing of apremilast and are suitable for treating diseases or disorders ameliorated by inhibiting phosphodiesterase subtype IV (PDE4).
Inventor(s):	William Brett Caldwell, Nathan Bennette, Christi Hostetler, Kazden Ingram, Dory King, Kyle Kyburz, Alison Viles
Assignee:	Bend Research Inc , Amgen Inc
Application Number:	US18/612,430
Patent Claims:	1. A method of treating a patient suffering from a disease or disorder ameliorated by inhibiting PDE4 comprising administering to a patient an oral dosage form comprising: a. a core tablet comprising (i) a drug layer comprising a water soluble polymer and a solid dispersion of amorphous apremilast and hypromellose acetate succinate (HPMCAS) in a weight ratio of 45:55 to 55:45, and (ii) a swellable layer comprising one or more swellable polymers; b. a coating layer disposed on the core tablet; and c. at least one drug release orifice on the dosage form surface, wherein the dosage form is administered once-a-day. 2. The method of claim 1, wherein the apremilast is present in an amount of 6-15 wt % of the core tablet. 3. The method form of claim 1, wherein the HPMCAS is present in an amount of 6-15 wt % of the core tablet. 4. The method of claim 1, wherein apremilast and HPMCAS are present in a weight ratio of 48:52 to 52:48 in the core tablet. 5. The method of claim 1, wherein the water soluble polymer comprises polyethylene oxide having an average molecular weight of 200 kDa or higher. 6. The method of claim 5, wherein the polyethylene oxide has an average molecular weight of 200-600 kDa. 7. The method of claim 1, wherein the water soluble polymer is present in an amount of 30-55 wt % of the core tablet. 8. The method of claim 1, wherein the water soluble polymer and apremilast are present in a weight ratio of 2 to 6:1, in the drug layer. 9. The method of claim 1, wherein the drug layer further comprises one or more of an osmotic agent, a diluent, and a lubricant. 10. The method of claim 9, wherein the drug layer comprises an osmotic agent. 11. The method of claim 10, wherein the osmotic agent comprises sodium chloride. 12. The method of claim 11, wherein the osmotic agent is present in the drug layer in an amount of 3-8 wt % of the core tablet. 13. The method of claim 1, wherein the swellable polymer comprises polyethylene oxide. 14. The method of claim 13, wherein the polyethylene oxide of the swellable layer has a higher average molecular weight of the polyethylene oxide in the drug layer. 15. The method of claim 14, wherein the polyethylene oxide of the swellable layer has an average molecular weight of 5,000 kDa. 16. The method of claim 1, wherein the swellable layer further comprises one or more of an osmotic agent, a diluent, and a lubricant. 17. The method of claim 16, wherein the swellable layer comprises an osmotic agent. 18. The method of claim 17, wherein the osmotic agent comprises sodium chloride. 19. The method of claim 1, wherein the drug layer and swellable layer are present in a weight ratio of 2:1 in the core tablet. 20. The method of claim 1, wherein the dosage form is administered under fed conditions. 21. The method of claim 1, wherein the disease or disorder is psoriasis. 22. The method of claim 1, wherein the disease or disorder is psoriatic arthritis. 23. The method of claim 1, wherein the disease or disorder is Behcet's disease. 24. The method of claim 1, wherein the apremilast is present in an amount of 8-11 wt % of the core tablet. 25. The method of claim 1, wherein the HPMCAS is present in an amount of 8-11 wt % of the core tablet. 26. The method of claim 1, wherein apremilast and HPMCAS are present in a weight ratio of 50:50. 27. The method of claim 1, wherein the coating layer comprises cellulose acetate and polyethylene oxide. 28. The method of claim 6, wherein the polyethylene oxide has an average molecular weight of 200 kDa. 29. The method of claim 1, wherein the drug layer further comprises extragranular mannitol. 30. The method of claim 29, wherein the extragranular mannitol is present in an amount of 2 wt % of the core tablet.