# US 11,998,548 B2 · Amorphous nilotinib microparticles and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,998,548 B2 - Document ID: US11998548B2 - Status: Granted - Kind: B2 - Application number: 18/090,582 - Filed: 2022-12-29 - Published: 2023-05-25 - Granted: 2024-06-04 - Earliest claimed: 2020-01-31 - Assignees: Nanocopoeia, LLC - Applicants: Nanocopoeia, LLC - Inventors: Christian F. Wertz; Tzehaw Chen; Joseph McTarsney - Web page: https://patentgrep.com/patent/US11998548B2 ## CPC - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/10: Dispersions; Emulsions - A61K 9/146: {with organic macromolecular compounds} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/38: Cellulose; Derivatives thereof - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 35/02: specific for leukemia - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Amorphous solid dispersions and pharmaceutical compositions of the protein kinase inhibitor nilotinib. The pharmaceutical compositions may be used in methods of treating a proliferative disorder such as cancer. In some embodiments, the pharmaceutical compositions can be administered without regard to food consumption. In other embodiments, the pharmaceutical compositions can be administered at a significantly lower dose as compared to a commercially available immediate-release nilotinib formulation, while providing a comparable therapeutic effect. ## Claims ### Claim 1 A method of delivering nilotinib to a patient suffering from a proliferative disorder, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion comprising nilotinib and one or more polymers; wherein the one or more polymers comprises an anionic polymer comprising phthalate functionality; wherein the nilotinib and the one or more polymers are present in the amorphous solid dispersion in a w/w ratio of 20:80 to 95:5 (nilotinib:polymer); and wherein the administered amount of nilotinib is 50 to 80% less than a dose required for delivering a therapeutically effective amount of nilotinib in the fasted state using a conventional immediate-release crystalline nilotinib formulation. ### Claim 2 (depends on 1) The method of claim 1, wherein the proliferative disorder is Philadelphia chromosome positive chronic myeloid leukemia. ### Claim 3 (depends on 1) The method of claim 1, wherein the nilotinib is present in the amorphous solid dispersion as nilotinib free base. ### Claim 4 (depends on 1) The method of claim 1, wherein the nilotinib is present in the amorphous solid dispersion as nilotinib hydrochloride. ### Claim 5 (depends on 1) The method of claim 1, wherein the anionic polymer comprising phthalate functionality includes hydroxypropyl methylcellulose phthalate. ### Claim 6 (depends on 1) The method of claim 1, wherein the anionic polymer comprising phthalate functionality includes polyvinyl acetate phthalate. ### Claim 7 (depends on 1) The method of claim 1, wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers. ### Claim 8 (depends on 1) The method of claim 1, wherein the amorphous solid dispersion includes one or more solubilizers. ### Claim 9 (depends on 8) The method of claim 8, wherein the one or more solubilizers comprises polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer. ### Claim 10 (depends on 8) The method of claim 8, wherein the one or more solubilizers comprises d-α-tocopherol acid polyethylene glycol (PEG) 1000 succinate. ### Claim 11 (depends on 1) The method of claim 1, wherein the amorphous solid dispersion consists essentially of nilotinib and the anionic polymer comprising phthalate functionality. ### Claim 12 (depends on 1) The method of claim 1, wherein the amorphous solid dispersion consists essentially of nilotinib and hydroxypropyl methylcellulose phthalate. ### Claim 13 (depends on 1) The method of claim 1, wherein the amorphous solid dispersion consists essentially of nilotinib and polyvinyl acetate phthalate. ### Claim 14 (depends on 1) The method of claim 1, wherein the nilotinib and the anionic polymer comprising phthalate functionality are present in the amorphous solid dispersion in a w/w ratio of 25:75 to 90:10 (nilotinib:polymer). ### Claim 15 (depends on 1) The method of claim 1, wherein the pharmaceutical composition comprises the amorphous solid dispersion and one or more pharmaceutically acceptable additives. ### Claim 16 (depends on 15) The method of claim 15, wherein the one or more pharmaceutically acceptable additives includes one or more solubilizers. ### Claim 17 (depends on 16) The method of claim 16, wherein the one or more solubilizers comprises polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer. ### Claim 18 (depends on 16) The method of claim 16, wherein the one or more solubilizers comprises d-α-tocopherol acid polyethylene glycol (PEG) 1000 succinate. ### Claim 19 (depends on 1) The method of claim 1, wherein the conventional immediate-release crystalline nilotinib formulation comprises 200 mg crystalline nilotinib monohydrochloride monohydrate presented in capsule form.