Claims for Patent: 10,874,671

Summary for Patent: 10,874,671

Title:	Pharmaceutical compositions of nilotinib
Abstract:	Amorphous solid dispersions of nilotinib fumarate or nilotinib tartrate are provided, as well as pharmaceutical compositions thereof, wherein the compositions exhibit enhanced bioavailability in the fasted state. Preferably, the compositions may be orally administered to a patient in either the fed or fasted state, with a decrease or elimination of the food effect. Preferably, following oral administration of the pharmaceutical compositions, there is no substantial difference in the pharmacokinetic parameters (e.g., Cmax, AUC0-t and/or AUC0-infinity) of nilotinib, regardless of whether the pharmaceutical compositions are administered to a subject in the fed or fasted state.
Inventor(s):	Paras P. JAIN, Ajay Kumar Singh, Keerthi Priya, Girish Kumar Jain, Girish G. KORE, Sandeep Jain, Hanimi Reddy BAPATU
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US16/793,833
Patent Claims:	1. An amorphous solid dispersion comprising nilotinib fumarate or nilotinib tartrate. 2. The amorphous solid dispersion according to claim 1, further comprising a pharmaceutically acceptable carrier, and optionally, at least one organic acid. 3. The amorphous solid dispersion according to claim 1, prepared by hot-melt extrusion or spray-drying. 4. The amorphous solid dispersion according to claim 2, wherein the weight ratio of the nilotinib fumarate or the nilotinib tartrate to the pharmaceutically acceptable carrier is from about 1:1 to about 1:6, preferably from about 1:3 to about 1:4. 5. The amorphous solid dispersion according to claim 2, wherein the pharmaceutically acceptable carrier is selected from the group consisting of hydroxypropyl methyl cellulose acetate succinate (HPMC-AS), polyvinyl pyrrolidine and vinyl acetate (PVP/VA) copolymer, hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), polyvinyl pyrrolidine (PVP), and mixtures thereof. 6. The amorphous solid dispersion according to claim 2, wherein the organic acid is selected from the group consisting of acetic acid, propionic acid, octanoic acid, decanoic acid, dodecanoic acid, glycolic acid, lactic acid, fumaric acid, succinic acid, adipic acid, pimelic acid, malic acid, tartaric acid, citric acid, glutamic acid, aspartic acid, maleic acid, benzoic acid, salicylic acid, phthalic acid, phenylacetic acid, cinnamic acid, ascorbic acid, and mixtures thereof. 7. The amorphous solid dispersion according to claim 6, wherein the weight ratio of the nilotinib fumarate or the nilotinib tartrate to the organic acid is from about 1:0.5 to about 1:5; preferably about 1:2; more preferably about 1:1. 8. The amorphous solid dispersion according to claim 2, further comprising one or more pharmaceutically acceptable excipients selected from the group consisting of diluents, binders, disintegrants, lubricants, glidants, surfactants, solubilizers, plasticizers, stabilizing agents, antioxidants and combinations thereof. 9. A pharmaceutical composition comprising an effective amount of an amorphous solid dispersion of nilotinib fumarate or nilotinib tartrate, wherein the solid dispersion comprises a pharmaceutically acceptable carrier and optionally at least one organic acid, and wherein the pharmaceutical composition provides enhanced bioavailability when compared to a reference formulation in fasted state. 10. The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition comprises from about 25 mg to about 200 mg of nilotinib fumarate or nilotinib tartrate. 11. The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is in the form of a tablet, a capsule, a caplet, beads, granules or oral suspension. 12. The pharmaceutical composition according to claim 9, further comprising one or more pharmaceutically acceptable excipients selected from the group consisting of diluents, binders, disintegrants, lubricants, glidants, surfactants, plasticizers, solubilizers, stabilizing agents, antioxidants and combinations thereof. 13. The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is obtained by direct compression, wet granulation or dry granulation. 14. The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is in the form of a tablet comprising: (a) an amorphous solid dispersion of nilotinib fumarate or nilotinib tartrate in the form of granules, (b) at least one intra-granular excipient, (c) at least one extra-granular excipient, and (d) optionally, a coating. 15. The pharmaceutical composition according to claim 9, wherein the composition remains stable for at least 6 months at 40° C./75% RH or 25° C./60% RH. 16. The pharmaceutical composition according to claim 9, wherein the level of any unknown impurity is less than about 0.2% (w/w), preferably less than about 0.15% (w/w), more preferably less than about 0.1% (w/w) as measured by HPLC. 17. A kit comprising: (a) a pharmaceutical composition according to claim 9; and (b) instructions for oral administration of the composition, wherein the instructions indicate that the composition can be administered to a human subject without regard to food. 18. A pharmaceutical composition comprising an effective amount of amorphous solid dispersion of nilotinib fumarate or nilotinib tartrate, wherein the solid dispersion further comprises a pharmaceutically acceptable carrier and optionally at least one organic acid, and wherein at least one pharmacokinetic parameter of nilotinib in a human subject subsequent to administration in the fasted state is from about 80% to about 125% of that pharmacokinetic parameter of nilotinib in a human subject subsequent to administration in the fed state, wherein the at least one pharmacokinetic parameter is selected from AUC0-infinity, Cmax, AUC0-t, or combinations thereof. 19. The amorphous solid dispersion according to claim 1, wherein the amorphous solid dispersion contains nilotinib fumarate or nilotinib tartrate in substantially amorphous form. 20. The amorphous solid dispersion according to claim 1, wherein the amorphous solid dispersion contains nilotinib fumarate or nilotinib tartrate in at least about 80% amorphous form. 21. The amorphous solid dispersion according to claim 1, wherein the amorphous solid dispersion contains nilotinib fumarate or nilotinib tartrate in at least about 90% amorphous form. 22. The amorphous solid dispersion according to claim 1, wherein the amorphous solid dispersion is characterized by an X-ray diffraction (XRD) profile substantially as shown in FIG. 2. 23. The amorphous solid dispersion according to claim 1, wherein the amorphous solid dispersion is characterized by an X-ray diffraction (XRD) profile substantially as shown in FIG. 3.