Claims for Patent: 10,617,638

Summary for Patent: 10,617,638

Title:	Stable pressurized aerosol solution composition of glycopyrronium bromide and formoterol combination
Abstract:	Aerosol solution compositions intended for use with a pressurized metered dose inhaler, comprising glycopyrronium bromide and formoterol, or a salt thereof or a solvate of said salt, optionally in combination with one or more additional active ingredients, and stabilized by a selected amount of a mineral acid, exhibit improved stability when contained in a can internally coated by a resin comprising a fluorinated ethylene propylene (FEP) polymer.
Inventor(s):	Sauro BONELLI, Diego COPELLI, Massimiliano Dagli Alberi, Francesca Usberti, Enrico Zambelli
Assignee:	Chiesi Farmaceutici SpA
Application Number:	US15/196,318
Patent Claims:	1. A pharmaceutical aerosol solution composition, for use in a pressurized metered dose inhaler, comprising: (a) glycopyrronium bromide at a dosage in the range of from 5 to 26 μg per actuation; (b) formoterol, or a salt thereof or a solvate of said salt, at a dosage in the range of from 1 to 25 μg per actuation; (c) a HFA propellant; (d) a co-solvent; (e) a stabilizing amount of a mineral acid; wherein said composition is contained in an aerosol can internally coated by a resin comprising a fluorinated ethylene propylene (FEP) polymer; and wherein the amount of the degradation product N-(3-bromo)-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl] phenyl]formamide (DP3)formed, when said composition is stored in accelerated conditions at 25° C. and 60% relative humidity (RH) for at least 6 months, is lower than 0.10% w/w, with respect to the theoretical formoterol fumarate content of 6 μg/actuation. 2. A pharmaceutical aerosol solution composition according to claim 1, wherein said mineral acid is present in an amount of acid equivalent to 0.15 to 0.28 μg/μl of 1M hydrochloric acid. 3. A pharmaceutical aerosol solution composition according to claim 2, wherein said mineral acid is present in an amount of acid equivalent to 0.200 to 0.240 μg/μl of 1M hydrochloric acid. 4. A pharmaceutical aerosol solution composition according to claim 3, wherein said mineral acid is present in an amount of acid equivalent to 0.200 to 0.227 μg/μl of 1M hydrochloric acid in the range from. 5. A pharmaceutical aerosol solution composition according to claim 1, wherein said co-solvent is ethanol. 6. A pharmaceutical aerosol solution composition according to claim 1, wherein said formoterol salt is formoterol fumarate. 7. A pharmaceutical aerosol solution composition according to claim 1, wherein said solvate form of the formoterol salt is formoterol fumarate dihydrate. 8. A pharmaceutical aerosol solution composition according to claim 1, further comprising one or more pharmaceutically active ingredients selected from the group consisting of a beta-2 agonist, an inhalation corticosteroid, an antimuscarinic agent, and a phosphodiesterase-4 inhibitor. 9. A pharmaceutical aerosol solution composition according to claim 8, wherein said inhalation corticosteroid is beclometasone dipropionate, budesonide or its 22R-epimer, ciclesonide, flunisolide, fluticasone propionate, fluticasone furoate, mometasone furoate, butixocort, triamcinolone acetonide, triamcinolone, methylprednisolone, prednisone, loteprednol, or rofleponide. 10. A pharmaceutical aerosol solution composition according to claim 9, wherein said inhalation corticosteroid is beclometasone dipropionate which is present in an amount of 50 to 250 μg per actuation. 11. A pharmaceutical aerosol solution composition according to claim 9, wherein said inhalation corticosteroid is budesonide which is present in an amount of 50 to 250 μg per actuation. 12. A pharmaceutical aerosol solution composition according to claim 1, wherein the level of formoterol degradation products formed, when said composition is stored in accelerated conditions at 25° C. and 60% relative humidity for at least 6 months, is lower than 10% w/w with respect to the theoretical formoterol fumarate content of 6 μg/actuation, and wherein the residual level of formoterol fumarate, when said composition is stored in accelerated conditions at 25° C. and 60% relative humidity for at least 6 months, is higher than 90% w/w with respect to its initial content. 13. A pharmaceutical aerosol solution composition according to claim 12, wherein the overall level formoterol degradation products formed, when said composition is stored in accelerated conditions at 25° C. and 60% relative humidity for at least 6 months, is lower than 2% w/w with respect to the theoretical formoterol fumarate content of 6 μg/actuation, and wherein the residual level of the formoterol fumarate, when said composition is stored in accelerated conditions at 25° C. and 60% relative humidity for at least 6 months, is higher than 95% w/w with respect to its initial content. 14. An aerosol can internally coated by a resin comprising a fluorinated ethylene propylene (FEP) polymer and containing a pharmaceutical aerosol solution composition comprising: (a) glycopyrronium bromide at a dosage in the range of from 5 to 26 μg per actuation; (b) formoterol, or a salt thereof or a solvate of said salt, at a dosage in the range of from 1 to 25 μg per actuation; (c) a HFA propellant; (d) a co-solvent; (e) a stabilizing amount of a mineral acid; and, (f) optionally, an inhalation corticosteroid; and wherein the amount of the degradation product N-(3-bromo)-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl] phenyl]formamide (DP3) formed, when said composition is stored in accelerated conditions at 25° C. and 60% relative humidity (RH) for at least 6 months, is lower than 0.10% w/w, with respect to the theoretical formoterol fumarate content of 6 μg/actuation. 15. A method for the treatment of an obstructive respiratory disorder selected from the group consisting of asthma and COPD, comprising administering an effective amount of a pharmaceutical aerosol solution composition according to claim 1 to a subject in need thereof. 16. The aerosol can according to claim 14, wherein the can is internally coated by a resin comprising a mixture of fluorinated ethylene propylene (FEP) and polyether sulfone (PES).