# US 11,077,076 B2 · Pharmaceutical composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,077,076 B2 - Document ID: US11077076B2 - Status: Granted - Kind: B2 - Application number: 16/883,016 - Filed: 2020-05-26 - Published: 2020-09-10 - Granted: 2021-08-03 - Earliest claimed: 2016-09-19 - Assignees: Mexichem Fluor S.A. De C.V. - Applicants: Mexichem Fluor S.A. De C.V. - Inventors: Stuart Corr; Timothy James Noakes - Web page: https://patentgrep.com/patent/US11077076B2 ## CPC - A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} - A61K 9/0078: {for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions} - A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]} - A61K 9/124: {characterised by the propellant} - A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) - A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids - A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61P 11/00: Drugs for disorders of the respiratory system - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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). ## Claims ### Claim 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. ### Claim 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. ### Claim 3 (depends on 1) The method of claim 1, wherein the at least one salmeterol compound is selected from salmeterol and salmeterol xinafoate. ### Claim 4 (depends on 1) The method of claim 1, wherein the drug component additionally comprises at least one long acting muscarinic antagonist (LAMA). ### Claim 5 (depends on 4) 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. ### Claim 6 (depends on 4) The method of claim 4, wherein the at least one long acting muscarinic antagonist is a pharmaceutically acceptable salt of glycopyrrolate. ### Claim 7 (depends on 1) The method of claim 1, wherein the drug component additionally comprises at least one corticosteroid. ### Claim 8 (depends on 7) 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. ### Claim 9 (depends on 7) The method of claim 7, wherein the at least one corticosteroid is selected from fluticasone and the pharmaceutically acceptable salts and esters thereof. ### Claim 10 (depends on 1) The method of claim 1, wherein the pharmaceutical composition further comprises a surfactant component comprising at least one surfactant compound. ### Claim 11 (depends on 1) The method of claim 1, wherein the pharmaceutical composition further comprises a polar excipient. ### Claim 12 (depends on 11) The method of claim 11, wherein the polar excipient is ethanol. ### Claim 13 (depends on 1) 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. ### Claim 14 (depends on 13) 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. ### Claim 15 (depends on 1) The method of claim 1, wherein the pharmaceutical composition is in the form of a suspension. ### Claim 16 (depends on 1) 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.