Pharmaceutical composition

Patent metadata

Field	Value
Publication number	US-11077076-B2
Application number	US-202016883016-A
Country	US
Kind code	B2
Filing date	May 26, 2020
Priority date	Sep 19, 2016
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

A pharmaceutical composition is described. The composition comprises: (i) a drug component comprising at least one salmeterol compound selected from salmeterol and the pharmaceutically acceptable derivatives thereof; and (ii) a propellant component comprising 1,1-difluoroethane (HFA-152a).

First claim

The invention claimed is:

1. A method of improving the stability of a pharmaceutical composition comprising a propellant component and a drug component comprising at least one salmeterol compound selected from salmeterol and the pharmaceutically acceptable salts thereof, said method comprising:
using a propellant component at least 90 weight % of which is 1,1-difluoroethane (HFA-152a), and
selecting the components and conditions for the preparation of the pharmaceutical composition to maintain the water content of the pharmaceutical composition below 500 ppm based on the total weight of the pharmaceutical composition.

2. A method of improving the stability of a pharmaceutical composition comprising a propellant component and a drug component comprising at least one salmeterol compound selected from salmeterol and the pharmaceutically acceptable salts thereof, said method comprising:
using a propellant component at least 90 weight % of which is 1,1-difluoroethane (HFA-152a), wherein the oxygen content of the resulting pharmaceutical composition is below 1000 ppm based on the total weight of the pharmaceutical composition.

3. The method of claim 1 , wherein the at least one salmeterol compound is selected from salmeterol and salmeterol xinafoate.

4. The method of claim 1 , wherein the drug component additionally comprises at least one long acting muscarinic antagonist (LAMA).

5. The method of claim 4 , wherein the at least one long acting muscarinic antagonist is selected from the group consisting of umeclidinium, ipratropium, tiotropium, aclidinium and the pharmaceutically acceptable salts thereof.

6. The method of claim 4 , wherein the at least one long acting muscarinic antagonist is a pharmaceutically acceptable salt of glycopyrrolate.

7. The method of claim 1 , wherein the drug component additionally comprises at least one corticosteroid.

8. The method of claim 7 , wherein the at least one corticosteroid is selected from the group consisting of budesonide, mometasone, beclomethasone, fluticasone and the pharmaceutically acceptable salts and esters thereof.

9. The method of claim 7 , wherein the at least one corticosteroid is selected from fluticasone and the pharmaceutically acceptable salts and esters thereof.

10. The method of claim 1 , wherein the pharmaceutical composition further comprises a surfactant component comprising at least one surfactant compound.

11. The method of claim 1 , wherein the pharmaceutical composition further comprises a polar excipient.

12. The method of claim 11 , wherein the polar excipient is ethanol.

13. The method of claim 1 , wherein the pharmaceutical composition after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 6 months will produce less than 0.4% by weight of impurities from the degradation of the at least one salmeterol compound based on the total weight of the at least one salmeterol compound and the impurities.

14. The method of claim 13 , wherein at least 98.0% by weight of the at least one salmeterol compound that is contained originally in the pharmaceutical composition immediately following preparation will be present in the composition after storage in uncoated aluminium containers at 40° C. and 75% relative humidity for 6 months.

15. The method of claim 1 , wherein the pharmaceutical composition is in the form of a suspension.

16. The method of claim 1 , wherein the pharmaceutical composition is stabilised compared to a pharmaceutical composition that uses 1,1,1,2-tetrafluoroethane (HFA-134a) or 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea) as the propellant but which is otherwise identical.

Assignees

• Mexichem Fluor Sa De Cv

Inventors

• Corr Stuart
• Noakes Timothy James

Classifications

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K9/0078

  for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions · CPC title

• A61K31/137 Primary

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title

• A61K31/56

  Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids · CPC title