Formulations of deferasirox and methods of making the same

1. A pharmaceutical composition comprising an amorphous solid dispersion of deferasirox (DFX) and one or more pharmaceutically acceptable excipients, wherein said composition has a single glass transition temperature.

2. The pharmaceutical composition of claim 1 , wherein said composition remains amorphous per x-ray diffraction analysis following storage in an open container at about 40° C., relative humidity of about 75%, at five weeks.

3. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises one or more polymers, a processing agent and/or a surfactant.

4. The pharmaceutical composition of claim 3 , wherein the one or more pharmaceutical polymers comprises an agent selected from the group consisting of poly(vinyl acetate)-co-polyvinylpyrrolidone) copolymer, ethylcellulose, hydroxypropylcellulose, cellulose acetate butyrate, poly(vinylpyrrolidone), poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), hydroxypropyl methylcellulose, ethylcellulose, hydroxyethylcellulose, sodium carboxymethyl-cellulose, dimethylaminoethyl methacrylate-methacrylic acid ester copolymer, ethylacrylate-methylmethacrylate copolymer, cellulose acetate phthalate, cellulose acetate trimelletate, poly(vinyl acetate) phthalate, hydroxypropylmethylcellulose phthalate, poly(methacrylate ethylacrylate) (1:1) copolymer, poly(methacrylate methylmethacrylate) (1:1) copolymer, poly(methacrylate methylmethacrylate) (1:2) copolymer, hydroxypropylmethylcellulose acetate succinate and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.

5. The pharmaceutical composition of claim 3 , wherein the surfactant comprises an agent selected from the group consisting of sodium dodecyl sulfate, dioctyl sodium sulphosuccinate, polyoxyethylene (20) sorbitan monooleate, glycerol polyethylene glycol oxystearate-fatty acid glycerol polyglycol esters-polyethylene glycols-glycerol ethoxylate, glycerol-polyethylene glycol ricinoleate-fatty acid esters of polyethyleneglycol-polyethylene glycols-ethoxylated glycerol, vitamin E TPGS, and sorbitan laurate, and the pharmaceutical polymer comprises an agent selected from a group consisting of poly(vinylpyrrolidone), hydroxypropylcellulose, poly(vinyl alcohol), hydroxypropyl methylcellulose, hydroxyethylcellulose, and sodium carboxymethyl-cellulose and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.

6. The pharmaceutical composition of claim 3 , wherein the one or more pharmaceutical polymers is/are a water soluble polymer(s).

7. The pharmaceutical composition of claim 6 , wherein the one or more pharmaceutical water soluble polymer(s) is/are selected from the group consisting of poly(vinyl acetate)-co-poly(vinylpyrrolidone) copolymer, poly(vinylpyrrolidone), cellulose acetate phthalate, poly(vinyl acetate) phthalate, hydroxypropylmethylcellulose phthalate, poly(methacrylate ethylacrylate) (1:1) copolymer, poly(methacrylate methylmethacrylate) (1:1) copolymer, poly(methacrylate methylmethacrylate) (1:2) copolymer, hydroxypropyl methylcellulose, hydroxypropylmethylcellulose acetate succinate, poly(vinyl alcohol), and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.

8. The pharmaceutical composition of claim 6 , wherein the DFX to water soluble pharmaceutical polymer ratio is about 2:3, 1:1, or 3:2.

9. The pharmaceutical composition of claim 1 , wherein the composition exhibits a drug loading of about 30%-60% DFX, about 40%-60% DFX, about 30% DFX, 35% DFX, 40% DFX, 45% DFX, 50% DFX, 55% DFX, or 60% DFX.

10. The pharmaceutical composition of claim 1 , wherein the composition has less than about 1.0% degradation products of deferasirox (DFX).

11. The pharmaceutical composition of claim 1 , wherein the purity of DFX used in said composition is about 95%, is about 99%, is about 99.5%, or is about 95% to about 100%.

12. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition does not contain a processing agent, and/or does not contain a plasticizer.

13. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition comprises about 90 mg DFX, about 125 mg DFX, about 250 mg DFX, about 360 mg DFX, or about 500 mg DFX.

14. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises a pharmaceutical polymer of high melt viscosity or a thermally labile pharmaceutical polymer.

15. The pharmaceutical composition of claim 1 , wherein the purity of said composition is about 95%, is about 99%, is about 99.5%, or is about 95% to about 100%.

16. The pharmaceutical composition of claim 1 , wherein the peak solubility of the DFX in the composition is greater than 400 μg/mL in an aqueous buffer with a pH range of 4 to 8.

17. The pharmaceutical composition of claim 1 , wherein peak solubility of a DFX and the reference standard DFX after an 8 hr dissolution test in an aqueous buffer with a pH range of 4 to 8 have a ratio of greater than 4:1.

18. The pharmaceutical composition of claim 1 , wherein in the AUC of the DFX in the composition and AUC of a reference standard DFX have a ratio that is greater than 4:3.

19. The pharmaceutical composition of claim 1 , wherein said composition is formulated as an oral dosage form.

20. The pharmaceutical composition of claim 19 , wherein the oral dosage form is a tablet, a capsule, or a sachet.

21. The pharmaceutical composition of claim 20 , wherein the tablet is a round flat tablet, a round concave tablet, an elongated tablet, or a minitab.

22. The pharmaceutical composition of claim 20 , wherein said oral dosage form is an extended release form, an immediate release form, a disintegrating tablet or an eroding tablet.

23. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises a lubricant.

24. The pharmaceutical composition of claim 23 , wherein the lubricant is magnesium stearate.