Solid Pharmaceutical Compositions for Treating HCV

Patent metadata

Field	Value
Publication number	US-2020282004-A1
Application number	US-201916654433-A
Country	US
Kind code	A1
Filing date	Oct 16, 2019
Priority date	Jun 26, 2015
Publication date	Sep 10, 2020
Grant date	—

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.

First claim

1 . A solid oral pharmaceutical dosage formulation comprising:
a first composition comprising:
50% to 80% by weight of one or more pharmaceutically acceptable polymers, and
100 mg Compound 1

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 80% by weight of one or more pharmaceutically acceptable polymers, and
40 mg Compound 2

wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the second composition;

wherein the formulation is a tablet comprising 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 three of the tablets to a population of healthy, non-fasted adult humans results in a mean C max value between about 333 ng/mL and about 1113 ng/mL for Compound 1.

2 . The solid oral pharmaceutical dosage formulation of claim 1 , wherein the first composition comprises a first amorphous solid dispersion comprising Compound 1.

3 . The solid oral pharmaceutical dosage formulation of claim 1 , wherein the second composition comprises a second amorphous solid dispersion comprising Compound 2.

4 . The solid oral pharmaceutical dosage formulation of claim 2 , wherein the first amorphous solid dispersion comprises the one or more pharmaceutically acceptable polymers.

5 . The solid oral pharmaceutical dosage formulation of claim 2 , wherein the first amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants.

6 . The solid oral pharmaceutical dosage formulation of claim 4 , wherein the first amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants.

7 . The solid oral pharmaceutical dosage formulation of claim 3 , wherein the second amorphous solid dispersion comprises the one or more pharmaceutically acceptable polymers.

8 . The solid oral pharmaceutical dosage formulation of claim 3 , wherein the second amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants.

9 . The solid oral pharmaceutical dosage formulation of claim 7 , wherein the second amorphous solid dispersion further comprises one or more pharmaceutically acceptable surfactants.

10 . The solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation of claim 11 , wherein the one or more pharmaceutically acceptable surfactants further comprise propylene glycol monocaprylate.

13 . The solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation 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 solid oral pharmaceutical dosage formulation of claim 1 , wherein the first layer further comprises a disintegrant.

21 . The solid oral pharmaceutical dosage formulation of claim 20 , wherein the disintegrant comprises Croscarmellose sodium.

22 . The solid oral pharmaceutical dosage formulation of claim 1 , wherein the first layer and the second layer further comprise a lubricant.

23 . The solid oral pharmaceutical dosage formulation of claim 22 , wherein the lubricant comprises sodium stearyl fumarate.

24 . A solid oral pharmaceutical dosage formulation comprising:
a first composition comprising:
50% to 80% by weight of one or more pharmaceutically acceptable polymers, and
100 mg Compound 1

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 80% by weight of one or more pharmaceutically acceptable polymers, and
40 mg Compound 2

wherein the weight percentage of the one or more pharmaceutically acceptable polymers is relative to the total weight of the second composition;

wherein the formulation is a tablet comprising 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 three of the tablets to a population of healthy, non-fasted adult humans results in a mean AUC value between about 1099 ng·h/mL and about 3680 ng/mL for Compound 1.

25 . A solid

Assignees

• Abbvie Inc

Inventors

• Sever Nancy E
• Westedt Ulrich
• Lander Ute
• Schneider Katrin
• Steitz Benedikt
• Mueller Thomas
• Reul Regina
• Obermiller Constanze
• Jayasankar Adivaraha
• Simon Michael
• Gao Yi
• Hach Harald
• Kyeremateng Samuel
• Asmus Katharina
• Tong Ping
• Zhu Donghua
• Naris Marius
• Garrett Colleen

Classifications

• A61K31/4985 Primary

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K9/146 Primary

  with organic macromolecular compounds · CPC title

• A61K38/06 Primary

  Tripeptides · CPC title

• A61K31/498

  Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title