Darunavir combination formulations

Patent metadata

Field	Value
Publication number	US-11654150-B2
Application number	US-201916697888-A
Country	US
Kind code	B2
Filing date	Nov 27, 2019
Priority date	Jul 7, 2011
Publication date	May 23, 2023
Grant date	May 23, 2023

Abstract

This invention relate to solid oral dosage forms of tire HIV inhibitor Darunavir and/or a pharmaceutically acceptable salt or solvate thereof, and combination formulation thereof.

First claim

The invention claimed is:

1. A process for preparing an oral dosage form comprising the steps of:
(a) providing a dried darunavir granulate consisting of:
(a) darunavir, and/or a pharmaceutically acceptable salt or solvate thereof,
(b) hypromellose, and
(c) water,

wherein the dried darunavir granulate is prepared by: (i) mixing water and hypromellose to form a first mixture, (ii) spraying the first mixture on a powder of darunavir and/or a pharmaceutically acceptable salt or solvate thereof, to form a wet darunavir granulate, and (iii) drying the wet darunavir granulate to produce the dried darunavir granulate, wherein the darunavir or pharmaceutically acceptable salt or solvate thereof is about 95% to about 99.9%, by weight relative to the total weight of the dried darunavir granulate;
(b) providing a second mixture comprising microcrystalline cellulose, silicon dioxide loaded with GS-9350, and a disintegrant;
(c) adding the dried darunavir granulate of step (a) to the second mixture of step (b) and dry-blending to form a blend;
(d) adding a lubricant to the blend and mixing to prepare a homogeneous mixture; and
(e) compressing the homogenous mixture to produce the oral dosage form.

2. The process of claim 1 , further comprising film-coating the oral dosage form.

3. The process of claim 1 , wherein the hypromellose is hypromellose 2910 15 Mpa·s.

4. The process of claim 1 , wherein the silicon dioxide loaded with GS-9350 is colloidal silicon dioxide loaded with GS-9350.

5. The process of claim 1 , wherein the oral dosage form includes free form equivalent of darunavir of from 400 mg to about 800 mg.

6. The process of claim 1 , wherein the average particle size of the darunavir granulate is between 100 μm and 500 μm.

7. The process of claim 1 , wherein the average particle size of the darunavir granulate is between 150 μm and 400 μm.

8. The process of claim 1 , wherein the average particle size of the darunavir granulate is about 300 μm.

9. The process of claim 1 , wherein the weight:weight ratio of darunavir:GS-9350 is in the range of from about 10:1 to about 4:5.

10. The process of claim 1 , wherein the weight:weight ratio of darunavir:GS-9350 is about 5:1.

11. The process of claim 1 , wherein the lubricant is magnesium stearate.

12. The process of claim 1 , wherein the disintegrant is crospovidone.

Assignees

• Janssen Sciences Ireland Unlimited Co
• Gilead Sciences Inc
• Janssen Sciences Ireland Uc

Inventors

• Delaet Urbain Alfons C
• Heyns Philip Erna H
• Jans Eugeen Maria Jozef
• Mertens Roel Jos M
• Van Der Avoort Geert

Classifications

• A61K9/1652

  Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623) · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K31/635 Primary

  having a heterocyclic ring, e.g. sulfadiazine · CPC title

• A61K9/2009

  Inorganic compounds · CPC title

• A61P37/04

  Immunostimulants · CPC title