Solid antiviral dosage forms

Patent metadata

Field	Value
Publication number	US-2016199374-A1
Application number	US-201615073767-A
Country	US
Kind code	A1
Filing date	Mar 18, 2016
Priority date	Jan 3, 2014
Publication date	Jul 14, 2016
Grant date	—

Abstract

The present disclosure relates to solid dosage forms comprising antiviral compounds and methods of using such dosage forms to treat antiviral infection.

First claim

What is claimed is:

1 . A solid dosage form comprising a first composition and a second composition, wherein:
the first composition comprises from 40 mg to 180 mg of

from 5 mg to 30 mg of

from 25 mg to 120 mg of ritonavir, 70-85% by weight of copovidone; and 5% to 10% by weight of a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants, wherein all percentages are weight percentages relative to the total weight of the first composition, and wherein Compound 1, Compound 2 and ritonavir are formulated in an amorphous solid dispersion;
the second composition comprises from 75 mg to 900 mg (free acid equivalent) of a sodium monohydrate salt of

20-40% copovidone, and 20-40% hypromellose, wherein all percentages are weight percentages relative to the total weight of the second composition;
when dissolved in 900 mL of a dissolution medium using a standard USP dissolution Apparatus 2 (paddle) operating at 100 RPM at 37° C., 50-60% Compound 1 in the solid dosage form is released within 1 hour, 50-60% Compound 2 in the solid dosage form is released within 1 hour, 50-60% ritonavir in the solid dosage form is released within 1 hour, and 0.5-2% Compound 4 in the solid dosage form is released within 1 hour, wherein the dissolution medium is 0.05 M sodium phosphate buffer (pH 6.8) with 15 mM cetyltrimethylammonium bromide (cTAB), and
the total weight of the solid dosage form is from 100 mg to 1600 mg.

2 . The solid dosage form of claim 1 , wherein the first composition comprises from 45 mg to 55 mg of Compound 1, from 7.5 mg to 9.5 mg of Compound 2, and from 30 mg to 37 mg of ritonavir, and the second composition comprises from 150 mg to 300 mg (free acid equivalent) of the sodium monohydrate salt of Compound 4.

3 . A method for treating hepatitis C virus (HCV) infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient at least one solid dosage form of claim 1 .

4 . A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient three solid dosage forms of claim 1 .

5 . A solid dosage form comprising a first composition and a second composition, wherein:
the first composition comprises from 40 mg to 180 mg of Compound 1, from 5 mg to 30 mg of Compound 2, from 25 mg to 120 mg of ritonavir, 70-85% by weight of copovidone; and 5% to 10% by weight of a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants, wherein all percentages are weight percentages relative to the total weight of the first composition, and wherein Compound 1, Compound 2 and ritonavir are formulated in an amorphous solid dispersion; the second composition comprises from 75 mg to 900 mg (free acid equivalent) of a sodium monohydrate salt of Compound 4, 20-40% copovidone, and 20-40% hypromellose, wherein all percentages are weight percentages relative to the total weight of the second composition; when dissolved in 900 mL of a dissolution medium using a standard USP dissolution Apparatus 2 (paddle) operating at 100 RPM at 37° C., 95-100% Compound 1 in the solid dosage form is released within 4 hours, 95-100% Compound 2 in the solid dosage form is released within 4 hours, 95-100% ritonavir in the solid dosage form is released within 4 hours, and 10-15% Compound 4 in the solid dosage form is released within 4 hours, wherein the dissolution medium is 0.05 M sodium phosphate buffer (pH 6.8) with 15 mM cTAB, and the total weight of the solid dosage form is from 1000 mg to 1600 mg.

6 . The solid dosage form of claim 5 , wherein the first composition comprises from 45 mg to 55 mg of Compound 1, from 7.5 mg to 9.5 mg of Compound 2, and from 30 mg to 37 mg of ritonavir, and the second composition comprises from 150 mg to 300 mg (free acid equivalent) of the sodium monohydrate salt of Compound 4.

7 . A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient at least one solid dosage form of claim 5 .

8 . A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient three solid dosage forms of claim 5 .

9 . A solid dosage form comprising a first composition and a second composition, wherein:
the first composition comprises from 40 mg to 180 mg of Compound 1, from 5 mg to 30 mg of Compound 2, from 25 mg to 120 mg of ritonavir, 70-85% by weight of copovidone; and 5% to 10% by weight of a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants, wherein all percentages are weight percentages relative to the total weight of the first composition, and wherein Compound 1, Compound 2 and ritonavir are formulated in an amorphous solid dispersion; the second composition comprises from 75 mg to 900 mg (free acid equivalent) of a sodium monohydrate salt of Compound 4, 20-40% copovidone, and 20-40% hypromellose, wherein all percentages are weight percentages relative to the total weight of the second composition; when dissolved in 900 mL of a dissolution medium using a standard USP dissolution Apparatus 2 (paddle) operating at 100 RPM at 37° C., 95-100% Compound 1 in the solid dosage form is released within 6 hours, 95-100% Compound 2 in the solid dosage form is released within 6 hours, 95-100% ritonavir in the solid dosage form is released within 6 hours, and 15-20% Compound 4 in the solid dosage form is released within 6 hours, wherein the dissolution medium is 0.05 M sodium phosphate buffer (pH 6.8) with 15 mM cTAB, and the total weight of the solid dosage form is 1000 mg to 1600 mg.

10 . The solid dosage form of claim 9 , wherein the first composition comprises from 45 mg to 55 mg of Compound 1, from 7.5 mg to 9.5 mg of Compound 2, and from 30 mg to 37 mg of ritonavir, and the second composition comprises from 150 mg to 300 mg (free acid equivalent) of the sodium monohydrate salt of Compound 4.

11 . A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient at least one solid dosage form of claim 9 .

12 . A method for treating HCV infection in a patient in need of such treatment, wherein the method comprises administering once daily to the patient three solid dosage forms of claim 9 .

13 . A solid dosage form comprising a first composition and a second composition, wherein:
the first composition comprises from 40 mg to 180 mg of Compound 1, from 5 mg to 30 mg of Compound 2, from 25 mg to 120 mg of ritonavir, 70-85% by weight of copovidone; and 5% to 10% by weight of a pharmaceutically acceptable surfactant or a combination of pharmaceutically acceptable surfactants, wherein all percentages are weight percentages relative to the total weight of the first composition, and wherein Compound 1, Compound 2 and ritonavir are formulated in an amorphous solid dispersion; the second composition comprises from 75 mg to 900 mg (free acid equivalent) of a sodium monohydrate salt of Compound 4, 20-40% copovidone, and 20-40% hypromellose, wherein all percentages are weight percentages relative to the total weight of the second composition; when dissolved in 900 mL o

Assignees

• Abbvie Inc

Inventors

• Miller Jonathan M
• Morris John B
• Sever Nancy E
• Schmitt Eric A
• Gao Ping X
• Shi Yi
• Gao Yi
• Liepold Bernd
• Moosmann Anna
• Pauli Mirko
• Durak Fatih
• Kessler Thomas
• Hoelig Peter
• Rosenblatt Karin
• Kostelac Drazen
• Gokhale Rajeev
• Costello Mark
• Knable Carl

Classifications

• A61K31/513 Primary

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K9/209

  containing drug in at least two layers or in the core and in at least one outer layer · CPC title

• A61K31/427

  not condensed and containing further heterocyclic rings · CPC title