Claims for Patent: 10,350,214

Summary for Patent: 10,350,214

Title:	Preparation containing tetracyclic compound at high dose
Abstract:	An improved solubility of a pharmaceutical composition or formulation containing a large amount of 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihy- dro-5H-benzo[b]carbazole-3-carbonitrile or a salt thereof can be achieved by forming granules of the compound or salt thereof and allowing the granules to be present together with a disintegrating agent.
Inventor(s):	Tomimatsu; Takashi (Tokyo, JP), Okazaki; Kensuke (Tokyo, JP), Ogawa; Yumi (Tokyo, JP), Yamamura; Takahiro (Tokyo, JP)
Assignee:	CHUGAI SEIYAKU KABUSHIKI KAISHA (Tokyo, JP)
Application Number:	15/304,133
Patent Claims:	1. A pharmaceutical formulation comprising (i) a granule containing a compound represented by formula (I) ##STR00004## or a salt thereof and (ii) carmellose calcium as a disintegrating agent, wherein the compound represented by formula (I) or a salt thereof is contained in an amount of 140 mg to 190 mg in terms of the free form per unit formulation. 2. The formulation according to claim 1, wherein the carmellose calcium (ii) is contained in an amount of 5 wt % or more based on the total amount of the formulation. 3. The formulation according to claim 1, wherein the carmellose calcium (ii) is contained in an amount of 7.5 wt % or more based on the total amount of the formulation. 4. The formulation according to claim 1, wherein the granule contains carmellose calcium therein. 5. The formulation according to claim 1, wherein the granule contains a solubilizing agent therein. 6. The formulation according to claim 5, wherein the solubilizing agent is sodium lauryl sulfate. 7. The formulation according to claim 6, wherein sodium lauryl sulfate is obtained by crystallization. 8. The formulation according to claim 5, wherein the weight ratio of the compound represented by formula (I) to the solubilizing agent is 100:2 to 100:60. 9. The formulation according to claim 8, wherein the compound represented by formula (I) or a salt thereof is contained in an amount of 35 to 60 wt % based on the total amount of the formulation. 10. The formulation according to claim 1, wherein the granule contains a binder therein. 11. The formulation according to claim 10, wherein the binder is hydroxypropylcellulose. 12. The formulation according to claim 1, wherein the granule has a mean particle diameter of 150 .mu.m or more. 13. The formulation according to claim 1, wherein the granule has a mean particle diameter of 200 .mu.m or more. 14. The formulation according to claim 1, wherein a compound represented by formula (I) or a salt thereof is contained in an amount of 20 to 70 wt % in terms of the free form based on the total amount of the formulation. 15. A method for producing a formulation improved in solubility of a compound represented by formula (I) ##STR00005## or a salt thereof, comprising (i) granulating a granule containing a compound represented by formula (I) or a salt thereof and (ii) blending carmellose calcium as a disintegrating agent and optionally other additives as external additives, wherein the compound represented by formula (I) or a salt thereof is contained in an amount of 140 mg to 190 mg in terms of the free form per unit formulation. 16. The method according to claim 15, wherein the carmellose calcium (ii) is contained in an amount of 7.5 wt % or more and 30 wt % or less based on the total amount of the formulation. 17. The method according to claim 15, wherein the granule has a mean particle diameter of 150 .mu.m or more and 1 mm or less. 18. The method according to claim 15, wherein the granule has a mean particle diameter of 180 .mu.m or more and 1 mm or less. 19. The method according to claim 15, wherein the granule (i) has carmellose calcium therein. 20. The method according to claim 15, wherein the granule contains a solubilizing agent therein. 21. The method according to claim 20, wherein the solubilizing agent is sodium lauryl sulfate obtained by crystallization. 22. The method according to claim 20, wherein a weight ratio of the compound represented by formula (I) to the solubilizing agent is 100:2 to 100:60. 23. The method according to claim 15, wherein the granule contains a binder therein. 24. The method according to claim 23, wherein the binder is hydroxypropylcellulose.