Stainless steel can for pressurised metered dose inhalers

Patent metadata

Field	Value
Publication number	US-2022395454-A1
Application number	US-201917776168-A
Country	US
Kind code	A1
Filing date	Dec 2, 2019
Priority date	Dec 2, 2019
Publication date	Dec 15, 2022
Grant date	—

Abstract

The invention generally refers to a stainless steel can for use in a metered dose inhaler device, containing an aerosol formulation, comprising glycopyrronium bromide and formoterol, or a salt or a solvate thereof, optionally in combination with one or more additional active ingredient, endowed with a high stability.

First claim

1 . A pharmaceutical aerosol solution formulation,
comprising: (a) glycopyrronium bromide at a dosage in the range of from 5 to 26 μg per actuation; (b) formoterol, or a salt or a solvate thereof, at a dosage in the range of from 1 to 25 μg per actuation; (c) a HFA propellant; (d) a co-solvent; (e) a mineral acid; and optionally (f) an inhalation corticosteroid said formulation being contained in an aerosol can made of stainless steel.

2 . The pharmaceutical aerosol solution formulation according to claim 1 , wherein said glycopyrronium bromide is present in an amount from 6 to 25 μg per actuation.

3 . The pharmaceutical aerosol solution formulation according to claim 1 , wherein said formoterol, or a salt or a solvate thereof is present in an amount from 6 to 12 μg per actuation.

4 . The pharmaceutical aerosol solution formulation according to claim 1 wherein the HFA propellant is HFA134a, HFA 227, HFA152a or a mixture thereof.

5 . The pharmaceutical aerosol solution formulation according to claim 1 , wherein the co-solvent is a (C 1 -C 4 ) alkyl alcohol.

6 . The pharmaceutical aerosol solution formulation according to claim 5 , wherein the co-solvent is ethanol in a concentration suitable to completely dissolve the active ingredients in the formulation.

7 . The pharmaceutical aerosol solution formulation according to claim 6 , wherein ethanol is anhydrous ethanol at a concentration comprised from 5 to 30% w/w on the total weight of the formulation.

8 . The pharmaceutical aerosol solution formulation according to claim 1 , wherein the mineral acid is a pharmaceutically acceptable monoprotic or polyprotic acid.

9 . The pharmaceutical aerosol solution formulation according to claim 8 , wherein the mineral acid is hydrochloric acid.

10 . The pharmaceutical aerosol solution formulation according to claim 9 , wherein the mineral acid is 1M hydrochloric acid in an amount in the range from 0.1 to 0.3 μg/μl of formulation.

11 . A pharmaceutical aerosol solution formulation according to claim 1 , characterised in that the amount of the degradation product N-(3-bromo)-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl]phenyl]formamide is lower than 0.10% w/w with respect to the theoretical formoterol fumarate content of 6 μg/actuation when stored in accelerated conditions at 25° C. and 60% relative humidity (RH) for at least 3 months.

12 . A pharmaceutical aerosol solution formulation according to claim 1 , wherein the formoterol salt is formoterol fumarate.

13 . A pharmaceutical aerosol solution formulation according to claim 1 , wherein the solvate form of the formoterol salt is formoterol fumarate dihydrate.

14 . A pharmaceutical aerosol solution formulation according to claim 1 , wherein the inhalation corticosteroid is selected from the group of beclometasone dipropionate, budesonide or its 22R-epimer, ciclesonide, flunisolide, fluticasone propionate, fluticasone furoate, mometasone furoate, butixocort, triamcinolone acetonide, triamcinolone, methylprednisolone, prednisone, loteprednol and rofleponide.

15 . A pharmaceutical aerosol solution formulation according to claim 14 wherein the inhalation corticosteroid is beclometasone dipropionate.

16 . A pharmaceutical aerosol solution formulation according to claim 15 , wherein the beclometasone dipropionate is present in an amount in the range from 50 to 250 μg per actuation.

17 . A pharmaceutical aerosol solution formulation according to claim 16 , wherein the beclometasone dipropionate is present in the amount of 100 or 200 μg per actuation.

18 . A pharmaceutical aerosol solution formulation according to claim 1 , wherein the overall formoterol degradation products level is lower than 10% w/w with respect to the theoretical formoterol fumarate content of 6 μg/actuation and the residual level of formoterol fumarate is higher than 90% w/w with respect to its initial content.

19 . A pharmaceutical aerosol solution formulation according to claim 1 , wherein the overall formoterol degradation products level is lower than 2% w/w with respect to the theoretical formoterol fumarate content of 6 μg/actuation and the residual level of the formoterol fumarate is higher than 95% w/w with respect to its initial content.

20 . An aerosol can made of stainless steel containing a pharmaceutical aerosol solution formulation according to claim 1 , suitable for use in a pressurised metered dose inhaler.

21 . A pressurised metered dose inhaler comprising a can according to claim 20 .

22 . A method to lower the amount of degradation product N-(3-bromo)-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl]phenyl]formamide (DP3) during the shelf-life of a pharmaceutical aerosol solution formulation according to claim 1 , said method being characterised in containing said aerosol solution formulation in an aerosol can made of stainless steel.

Assignees

• Chiesi Farm Spa

Inventors

• Zambelli Enrico
• Bonelli Sauro
• Copelli Diego
• Dagli Alberi Massimiliano
• Usberti Francesca

Classifications

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61K9/008 Primary

  comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI] · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title