Claims for Patent: 11,246,866

Summary for Patent: 11,246,866

Title:	Solid pharmaceutical compositions for treating HCV
Abstract:	The present invention features solid pharmaceutical compositions comprising Compound 1 and Compound 2. In one embodiment, the solid pharmaceutical composition includes (1) a first layer which comprises 100 mg Compound 1, as well as a pharmaceutically acceptable hydrophilic polymer and a pharmaceutically acceptable surfactant, all of which are formulated in amorphous solid dispersion; and (2) a second layer which comprises 40 mg Compound 2, as well as a pharmaceutically acceptable hydrophilic polymer and a pharmaceutically acceptable surfactant, all of which are formulated in amorphous solid dispersion.
Inventor(s):	Sever; Nancy E. (Northbrook, IL), Westedt; Ulrich (Schriesheim, DE), Lander; Ute (Dannenfels, DE), Schneider; Katrin (Mannheim, DE), Steitz; Benedikt (Kallstadt, DE), Mueller; Thomas (Ludwigshafen, DE), Reul; Regina (Mannheim, DE), Obermiller; Constanze (Heidelberg, DE), Jayasankar; Adivaraha (Naperville, IL), Simon; Michael (Landau, DE), Gao; Yi (Vernon Hills, IL), Hach; Harald (Oberotterbach, DE), Kyeremateng; Samuel (Mannheim, DE), Asmus; Katharina (Neustadt a.d.W., DE), Tong; Ping (Potomoc, MD), Zhu; Donghua (Vernon Hills, IL), Naris; Marius (Downers Grove, IL), Garrett; Colleen (Chicago, IL)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	16/654,442
Patent Claims:	1. A solid oral pharmaceutical tablet comprising: a first composition comprising: 50% to 80% by weight of one or more pharmaceutically acceptable polymers, and 100 mg Compound 1 ##STR00003## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the first composition; and a second composition comprising: 50% to 90% by weight of one or more pharmaceutically acceptable polymers, and 40 mg Compound 2 ##STR00004## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the second composition; wherein the tablet comprises a first layer and a second layer, the first layer comprising the first composition and the second layer comprising the second composition; and wherein administration of a single dose comprising three of the tablets delivered at the same time to each individual in a population of healthy, non-fasted adult humans results in a mean Cmax value between about 333 ng/mL and about 1113 ng/mL for Compound 1. 2. The pharmaceutical tablet of claim 1, wherein the first composition comprises a first amorphous solid dispersion comprising Compound 1. 3. The pharmaceutical tablet of claim 1, wherein the second composition comprises a second amorphous solid dispersion comprising Compound 2. 4. The pharmaceutical tablet of claim 2, wherein the first amorphous solid dispersion comprises the one or more pharmaceutically acceptable polymers. 5. The pharmaceutical tablet of claim 2, wherein the first amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants. 6. The pharmaceutical tablet of claim 4, wherein the first amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants. 7. The pharmaceutical tablet of claim 3, wherein the second amorphous solid dispersion comprises the one or more pharmaceutically acceptable polymers. 8. The pharmaceutical tablet of claim 3, wherein the second amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants. 9. The pharmaceutical tablet of claim 7, wherein the second amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants. 10. The pharmaceutical tablet of claim 6, wherein the one or more pharmaceutically acceptable polymers comprise copovidone, and the one or more pharmaceutically acceptable surfactants comprise Vitamin E TPGS. 11. The pharmaceutical tablet of claim 9, wherein the one or more pharmaceutically acceptable polymers comprise copovidone, and the one or more pharmaceutically acceptable surfactant comprises Vitamin E TPGS. 12. The pharmaceutical tablet of claim 11, wherein the one or more pharmaceutically acceptable surfactants further comprise propylene glycol monocaprylate. 13. The pharmaceutical tablet of claim 1, wherein the first composition comprises a first amorphous solid dispersion comprising Compound 1, one or more pharmaceutically acceptable polymers and one or more pharmaceutically acceptable surfactants; and the second composition comprises a second amorphous solid dispersion comprising Compound 2, one or more pharmaceutically acceptable polymers and one or more pharmaceutically acceptable surfactants. 14. The pharmaceutical tablet of claim 13, wherein the one or more pharmaceutically acceptable polymers comprise copovidone, and the one or more pharmaceutically acceptable surfactants comprises Vitamin E TPGS. 15. The pharmaceutical tablet of claim 3, wherein the first amorphous solid dispersion comprises Compound 1, one or more pharmaceutically acceptable polymers comprising copovidone, and one or more pharmaceutically acceptable surfactants comprises Vitamin E TPGS; and the second amorphous solid dispersion comprises Compound 2, one or more pharmaceutically acceptable polymers comprising copovidone, and one or more pharmaceutically acceptable surfactants comprising Vitamin E TPGS and Propylene glycol monocaprylate. 16. The pharmaceutical tablet of claim 1, wherein the first amorphous solid dispersion comprises 10% to 40% by weight of Compound 1, and the second amorphous solid dispersion comprises 5% to 20% by weight of Compound 2. 17. The pharmaceutical tablet of claim 1, wherein the first amorphous solid dispersion comprises 15% to 30% by weight of Compound 1, and the second amorphous solid dispersion comprises 5% to 15% by weight of Compound 2. 18. The pharmaceutical tablet of claim 13, wherein the first amorphous solid dispersion comprises 15% to 30% by weight of Compound 1, and the second amorphous solid dispersion comprises 5% to 15% by weight of Compound 2. 19. The pharmaceutical tablet of claim 15, wherein the first amorphous solid dispersion comprises 15% to 30% by weight of Compound 1, and the second amorphous solid dispersion comprises 5% to 15% by weight of Compound 2. 20. The pharmaceutical tablet of claim 1, wherein the first layer further comprises a disintegrant. 21. The pharmaceutical tablet of claim 20, wherein the disintegrant comprises Croscarmellose sodium. 22. The pharmaceutical tablet of claim 1, wherein the first layer and the second layer further comprise a lubricant. 23. The pharmaceutical tablet of claim 22, wherein the lubricant comprises sodium stearyl fumarate. 24. A solid oral pharmaceutical tablet comprising: a first composition comprising: 50% to 80% by weight of one or more pharmaceutically acceptable polymers, and 100 mg Compound 1 ##STR00005## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the first composition; and a second composition comprising: 50% to 90% by weight of one or more pharmaceutically acceptable polymers, and 40 mg Compound 2 ##STR00006## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the second composition; wherein the tablet comprises a first layer and a second layer, the first layer comprising the first composition and the second layer comprising the second composition; and wherein administration of a single dose comprising three of the tablets delivered at the same time to each individual in a population of healthy, non-fasted adult humans results in a mean AUC value between about 1099 ngh/mL and about 3680 ngh/mL for Compound 1. 25. A solid oral pharmaceutical tablet comprising: a first composition comprising: 50% to 80% by weight of one or more pharmaceutically acceptable polymers, and 100 mg Compound 1 ##STR00007## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the first composition; and a second composition comprising: 50% to 90% by weight of one or more pharmaceutically acceptable polymers, and 40 mg Compound 2 ##STR00008## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the second composition; wherein the tablet comprises a first layer and a second layer, the first layer comprising the first composition and the second layer comprising the second composition; and wherein administration of a single dose comprising three of the tablets delivered at the same time to each individual in a population of healthy, fasted adult humans results in a mean C.sub.max value between about 85 ng/mL and about 684 ng/mL for Compound 1. 26. A solid oral pharmaceutical tablet comprising: a first composition comprising: 50% to 80% by weight of one or more pharmaceutically acceptable polymers, and 100 mg Compound 1 ##STR00009## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the first composition; and a second composition comprising: 50% to 90% by weight of one or more pharmaceutically acceptable polymers, and 40 mg Compound 2 ##STR00010## wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the second composition; wherein the tablet comprises a first layer and a second layer, the first layer comprising the first composition and the second layer comprising the second composition; and wherein administration of a single dose comprising three of the tablets delivered at the same time to each individual in a population of healthy, fasted adult humans results in a mean AUC value between about 429 ngh/mL and about 2431 ngh/mL for Compound 1. 27. A solid oral pharmaceutical tablet that is bioequivalent to a solid oral pharmaceutical tablet comprising: a. 500 mg of Compound 1 20% extrusion granulation, comprising: i. 20% (100 mg) Compound 1, ii. 69% copovidone, iii. 10% vitamin E TPGS, and iv. 1% colloidal silicon dioxide; b. 400 mg of Compound 2 10% extrusion granulation, comprising i. 10% (40 mg) Compound 2, ii. 79% copovidone, iii. 8% vitamin E TPGS, iv. 2% propylene glycol monocaprylate, and v. 1% colloidal silicone dioxide; c. 26.3 mg croscarmellose sodium; d. 4.7 mg colloidal silicon dioxide; e. 4.7 mg sodium stearyl fumarate; and f. 28.1 mg HPMC coating.