Claims for Patent: 11,160,804

Summary for Patent: 11,160,804

Title:	Pharmaceutical dosage forms
Abstract:	The present invention relates to solid pharmaceutical dosage forms comprising the drug substance 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimidin-4-yl}-1-methyl-urea or any pharmaceutically acceptable salt thereof. It further relates to processes of making said solid pharmaceutical dosage forms.
Inventor(s):	Ribeiro; Suzie Jesus (Basel, CH)
Assignee:	Novartis AG (Basel, CH)
Application Number:	16/364,727
Patent Claims:	1. A process for making a capsule for oral administration comprising: mixing a phosphate salt of the drug substance 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)phe- nylaminol-pyrimidin-4-yl}-1-methyl-urea, hydroxypropylmethylcellulose, crosslinked polyvinylpyrrolidone, and a filler selected from the group consisting of a cellulose, lactose, mannitol, and combinations thereof to obtain a dry blend; adding water to the dry blend to obtain a wet granulation mixture; kneading the wet granulation mixture to obtain granules; drying the granules to form an inner phase; combining the inner phase with one or more outer phase excipients to obtain a pharmaceutical blend; and filling a capsule with the pharmaceutical blend, wherein the pharmaceutical blend comprises (a) 20-60% by weight of the drug substance 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimidin-4-yl}-1-methyl-urea in its free base form, present as mono-phosphate salt, (b) 0.5-5% by weight of hydroxypropylmethylcellulose, (c) 1-4% by weight of crosslinked polyvinylpyrrolidone, and (d) a filler selected from the group consisting of a cellulose, lactose, mannitol, and combinations thereof; wherein the weight percentages are based on the total weight of the pharmaceutical blend content of the capsule. 2. The process of claim 1, wherein the one or more outer phase excipients is selected from the group consisting of a glidant, a lubricant, or combinations thereof. 3. A capsule for oral administration formed by the process of claim 1, wherein the pharmaceutical blend has a poured bulk density of at least 0.4 g/mL and comprises (a) 20-60% by weight of the drug substance 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimidin-4-yl}-1-methyl-urea in its free base form, present as mono-phosphate salt, (b) 0.5-5% by weight of hydroxypropylmethylcellulose, (c) 1-4% by weight of crosslinked polyvinylpyrrolidone, and (d) a filler selected from the group consisting of a cellulose, lactose, mannitol, and combinations thereof; wherein the weight percentages are based on the total weight of the pharmaceutical blend content of the capsule. 4. The process of claim 1, wherein the pharmaceutical blend comprises 2-4% by weight of hydroxypropylmethylcellulose, based on the total weight of the pharmaceutical blend. 5. The process of claim 4, wherein the pharmaceutical blend comprises 2-4% by weight of crosslinked polyvinylpyrrolidone, based on the total weight of the pharmaceutical blend. 6. A process for making a capsule for oral administration comprising: (i) wet granulating a phosphate salt of the drug substance 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimidin-4-yl}-1-methyl-urea, with hydroxypropylmethylcellulose, crosslinked polyvinylpyrrolidone, a filler selected from the group consisting of a cellulose, lactose, mannitol and combinations thereof, and an aqueous granulating fluid, to obtain granules; (ii) mixing the granules with one or more pharmaceutical excipients, to obtain a pharmaceutical blend; and (iii) filling a capsule with the pharmaceutical blend, wherein the pharmaceutical blend comprises (a) 20-60% by weight of the drug substance 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimidin-4-yl}-1-methyl-urea in its free base form, present as mono-phosphate salt, (b) 0.5-5% by weight of hydroxypropylmethylcellulose, (c) 1-4% by weight of crosslinked polyvinylpyrrolidone, and (d) a filler selected from the group consisting of a cellulose, lactose, mannitol, and combinations thereof; wherein the weight percentages are based on the total weight of the pharmaceutical blend content of the capsule. 7. The process of claim 6, wherein the one or more pharmaceutical excipients is selected from the group consisting of a glidant, a lubricant, or combinations thereof. 8. The process of claim 6, wherein the pharmaceutical blend comprises 2-4% by weight of hydroxypropylmethylcellulose, based on the total weight of the pharmaceutical blend. 9. The process of claim 8, wherein the pharmaceutical blend comprises 2-4% by weight of crosslinked polyvinylpyrrolidone, based on the total weight of the pharmaceutical blend. 10. A capsule for oral administration formed by the process of claim 6, wherein the pharmaceutical blend has a poured bulk density of at least 0.4 g/mL and comprises (a) 20-60% by weight of the drug substance 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-ph- enylamino]-pyrimidin-4-yl}-1-methyl-urea in its free base form, present as mono-phosphate salt, (b) 0.5-5% by weight of hydroxypropylmethylcellulose, (c) 1-4% by weight of crosslinked polyvinylpyrrolidone, and (d) a filler selected from the group consisting of a cellulose, lactose, mannitol, and combinations thereof; wherein the weight percentages are based on the total weight of the pharmaceutical blend content of the capsule.