Claims for Patent: 11,723,874

Summary for Patent: 11,723,874

Title:	Delayed release deferiprone tablets and methods of using the same
Abstract:	The invention is directed to pharmaceutical compositions such as tablets that exhibit delayed release properties when administered as either whole or half tablets. The invention is also directed to delayed release tablets comprising deferiprone for oral administration, for which twice daily administration is bioequivalent to the same daily dose of an immediate release tablet administered thrice daily. The invention is also directed to methods of making and using the same.
Inventor(s):	Bernard Charles Sherman, Michael Spino
Assignee:	Chiesi Farmaceutici SpA
Application Number:	US17/327,135
Patent Claims:	1. A method for treating transfusional iron overload in a patient with thalassemia syndromes, comprising orally administering to the patient a tablet comprising: (a) a core comprising (i) about 1000 mg deferiprone, (ii) an enteric polymer in an amount of about 1% to about 5% by weight of the core, (iii) a pH adjusting agent, and (iv) a glidant, and (b) an enteric coating comprising (i) a plasticizer, (ii) an anti-tacking agent, (iii) an opacifying agent, and (iv) an enteric polymer. 2. The method of claim 1, wherein the tablet is administered to the subject as one or more whole tablets, one or more half tablets, or a combination thereof. 3. The method of claim 1, wherein the enteric polymer in the core is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMCAS), HPMC phthalate, polyvinyl acetate phthalate, a methacrylic acid copolymer, a derivative thereof, and a combination thereof. 4. The method of claim 1, wherein the pH adjusting agent is selected from the group consisting of meglumine, metal oxides, metal hydroxides, basic salts of weak acids, and a combination thereof. 5. The method of claim 1, wherein the core further comprises a lubricant selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, and a combination thereof. 6. The method of claim 1, wherein the core comprises: (i) about 1000 mg deferiprone; (ii) the enteric polymer in an amount of about 1% to about 5% by weight of the core; (iii) the pH adjusting agent in an amount of about 2% to about 8% by weight of the core; (iv) the glidant in an amount of about 0.1% to about 0.5% by weight of the core; and (v) a lubricant in an amount of about 0.5% to about 2% by weight of the core. 7. The method of claim 1, wherein the enteric polymer in the core comprises hydroxypropyl methylcellulose acetate succinate (HPMCAS), the pH adjusting agent in the core comprises magnesium oxide, and the glidant in the core comprises colloidal silicon dioxide. 8. The method of claim 7, wherein the core further comprises a lubricant selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, and a combination thereof. 9. The method of claim 1, wherein the enteric polymer in the coating is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMCAS), HPMC phthalate, polyvinyl acetate phthalate, a methacrylic acid copolymer, cellulose acetate phthalate, cellulose acetate trimellitate, shellac, zein, a derivative thereof, and a combination thereof. 10. The method of claim 1, wherein the plasticizer is selected from the group consisting of diethyl phthalate, citrate esters, polyethylene glycol, glycerol, acetylated glycerides, acetylated citrate esters, dibutyl sebecate, castor oil, or any combination thereof. 11. The method of claim 1, wherein the enteric polymer in the coating comprises a methacrylic acid copolymer, the plasticizer in the coating comprises a citrate ester, the anti-tacking agent in the coating comprises talc, and the opacifying agent in the coating comprises titanium dioxide. 12. The method of claim 8, wherein the lubricant comprises magnesium stearate, and wherein the core comprises: (i) about 1000 mg deferiprone; (ii) about 25 mg to about 35 mg hydroxypropyl methylcellulose acetate succinate (HPMCAS); (iii) about 40 to about 60 mg magnesium oxide; (iv) about 5 mg colloidal silicon dioxide; and (v) about 15 to about 20 mg magnesium stearate. 13. The method of claim 1, wherein the tablet is administered in an amount of from 50 mg/kg/day to about 100 mg/kg/day. 14. A method for treating transfusional iron overload in a patient with sickle cell disease, comprising orally administering to the patient a tablet comprising: (a) a core comprising (i) about 1000 mg deferiprone, (ii) an enteric polymer in an amount of about 1% to about 5% by weight of the core, (iii) a pH adjusting agent, and (iv) a glidant, and (b) an enteric coating comprising (i) a plasticizer, (ii) an anti-tacking agent, (iii) an opacifying agent, and (iv) an enteric polymer. 15. The method of claim 14, wherein the tablet is administered to the subject as one or more whole tablets, one or more half tablets, or a combination thereof. 16. The method of claim 14, wherein the enteric polymer in the core is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMCAS), HPMC phthalate, polyvinyl acetate phthalate, a methacrylic acid copolymer, a derivative thereof, and a combination thereof. 17. The method of claim 14, wherein the pH adjusting agent is selected from the group consisting of meglumine, metal oxides, metal hydroxides, basic salts of weak acids, and a combination thereof. 18. The method of claim 14, wherein the core further comprises a lubricant selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, and a combination thereof. 19. The method of claim 14, wherein the core comprises: (i) about 1000 mg deferiprone; (ii) the enteric polymer in an amount of about 1% to about 5% by weight of the core; (iii) the pH adjusting agent in an amount of about 2% to about 8% by weight of the core; (iv) the glidant in an amount of about 0.1% to about 0.5% by weight of the core; and (v) a lubricant in an amount of about 0.5% to about 2% by weight of the core. 20. The method of claim 14, wherein the enteric polymer in the core comprises hydroxypropyl methylcellulose acetate succinate (HPMCAS), the pH adjusting agent in the core comprises magnesium oxide, and the glidant in the core comprises colloidal silicon dioxide. 21. The method of claim 20, wherein the core further comprises a lubricant selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, and a combination thereof. 22. The method of claim 14, wherein the enteric polymer in the coating is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMCAS), HPMC phthalate, polyvinyl acetate phthalate, a methacrylic acid copolymer, cellulose acetate phthalate, cellulose acetate trimellitate, shellac, zein, a derivative thereof, and a combination thereof. 23. The method of claim 14, wherein the plasticizer is selected from the group consisting of diethyl phthalate, citrate esters, polyethylene glycol, glycerol, acetylated glycerides, acetylated citrate esters, dibutyl sebecate, castor oil, or any combination thereof. 24. The method of claim 14, wherein the enteric polymer in the coating comprises a methacrylic acid copolymer, the plasticizer in the coating comprises a citrate ester, the anti-tacking agent in the coating comprises talc, and the opacifying agent in the coating comprises titanium dioxide. 25. The method of claim 21, wherein the lubricant comprises magnesium stearate, and wherein the core comprises: (i) about 1000 mg deferiprone; (ii) about 25 mg to about 35 mg hydroxypropyl methylcellulose acetate succinate (HPMCAS); (iii) about 40 to about 60 mg magnesium oxide; (iv) about 5 mg colloidal silicon dioxide; and (v) about 15 to about 20 mg magnesium stearate. 26. The method of claim 14, wherein the tablet is administered in an amount of from 50 mg/kg/day to about 100 mg/kg/day. 27. A method for treating transfusional iron overload, comprising orally administering to the patient a tablet comprising: (a) a core comprising (i) about 1000 mg deferiprone, (ii) an enteric polymer in an amount of about 1% to about 5% by weight of the core, (iii) a pH adjusting agent, and (iv) a glidant, and (b) an enteric coating comprising (i) a plasticizer, (ii) an anti-tacking agent, (iii) an opacifying agent, and (iv) an enteric polymer.