Crystalline microparticles of a beta-agonist coated with a fatty acid

Patent metadata

Field	Value
Publication number	US-2016324792-A1
Application number	US-201615152835-A
Country	US
Kind code	A1
Filing date	May 12, 2016
Priority date	Oct 11, 2011
Publication date	Nov 10, 2016
Grant date	—

Abstract

Crystalline microparticles consisting of a phenylalkylamino beta 2 -adrenergic agonist coated with a C12-C20 fatty acid are useful for the preparation of pharmaceutical aerosol formulations in form of suspension in a liquefied propellant gas or powder formulations.

First claim

1 - 11 . (canceled)

12 . A process for preparing chemically stable crystalline microparticles, comprising a beta 2 -adrenergic agonist selected from the group consisting of formoterol, a pharmaceutically acceptable salt of formoterol, indacaterol, and a pharmaceutically acceptable salt of indacaterol, coated with at least one C12-C20 fatty acid in an amount of 0.5 to 2.0% by weight based on a total weight of the crystalline microparticles, the process comprising:
(a) preparing a solution of the C12-C20 fatty acid in a fluorinated model propellant in which the beta 2 -agonist is substantially insoluble, selected from the group consisting of perfluoropentane, 2H,3H-perfluoropentane (HPFP), perfluorohexane, and 1H-perfluorohexane; (b) adding the beta 2 -agonist as a micronized powder to said solution of the fatty acid, to obtain a mixture; (c) mixing the mixture to obtain a homogeneous suspension; and (d) subjecting the suspension to spray-drying, to obtain the coated microparticles; wherein the fatty acid forms a continuous film on a surface of the microparticles.

13 . The process according to claim 12 , wherein the fluorinated model propellant is 2H,3H-perfluoropentane (HPFP).

14 - 16 . (canceled)

17 . The process according to claim 12 , wherein the beta 2 -adrenergic agonist is formoterol.

18 . The process according to claim 17 , wherein the fluorinated model propellant is 2H,3H-perfluoropentane (HPFP).

19 . The process according to claim 17 , wherein:
the C14-C20 saturated fatty acid is myristic acid; and the myristic acid is present in an amount of 1.0 to 2.0% by weight based on the total weight of the crystalline microparticles.

20 . The process according to claim 17 , further comprising:
preparing a pharmaceutical aerosol formulation comprising the coated microparticles in suspension in a liquefied propellant gas; and filling the pharmaceutical aerosol formulation into a pressurized metered dose inhaler.

21 . The process according to claim 20 , wherein the liquefied propellant gas is 1,1,1,2,3,3,3-heptafluoro-n-propane (HFA227) or 1,1,1,2-tetrafluoroethane (HFA 134a), or a mixture thereof.

22 . The process according to claim 20 , wherein the formulation, upon storage, meets the requirements of EMEA Guideline CPMP/QWP/122/02.

23 . The process according to claim 17 , further comprising preparing a dry powder pharmaceutical formulation comprising the coated microparticles.

24 . The process according to claim 12 , wherein the beta2-adrenergic agonist is a fumarate dihydrate salt of formoterol.

25 . The process according to claim 24 , wherein the fluorinated model propellant is 2H,3H-perfluoropentane (HPFP).

26 . The process according to claim 24 , wherein:
the C14-C20 saturated fatty acid is myristic acid; and the myristic acid is present in an amount of 1.0 to 2.0% by weight based on the total weight of the crystalline microparticles.

27 . The process according to claim 24 , further comprising:
preparing a pharmaceutical aerosol formulation comprising the coated microparticles in suspension in a liquefied propellant gas; and filling the pharmaceutical aerosol formulation into a pressurized metered dose inhaler.

28 . The process according to claim 27 , wherein the liquefied propellant gas is 1,1,1,2,3,3,3-heptafluoro-n-propane (HFA227) or 1,1,1,2-tetrafluoroethane (HFA 134a), or a mixture thereof.

29 . The process according to claim 27 , wherein the formulation, upon storage, meets the requirements of EMEA Guideline CPMP/QWP/122/02.

30 . The process according to claim 24 , further comprising preparing a dry powder pharmaceutical formulation comprising the coated microparticles.

31 . The process according to claim 12 , wherein the beta 2 -adrenergic agonist is indacaterol.

32 . The process according to claim 31 , wherein the fluorinated model propellant is 2H,3H-perfluoropentane (HPFP).

33 . The process according to claim 31 , wherein:
the C14-C20 saturated fatty acid is myristic acid; and the myristic acid is present in an amount of 1.0 to 2.0% by weight based on the total weight of the crystalline microparticles.

34 . The process according to claim 31 , further comprising:
preparing a pharmaceutical aerosol formulation comprising the coated microparticles in suspension in a liquefied propellant gas; and filling the pharmaceutical aerosol formulation into a pressurized metered dose inhaler.

35 . The process according to claim 34 , wherein the liquefied propellant gas is 1,1,1,2,3,3,3-heptafluoro-n-propane (HFA227) or 1,1,1,2-tetrafluoroethane (HFA 134a), or a mixture thereof.

36 . The process according to claim 34 , wherein the formulation, upon storage, meets the requirements of EMEA Guideline CPMP/QWP/122/02.

37 . The process according to claim 31 , further comprising preparing a dry powder pharmaceutical formulation comprising the coated microparticles.

38 . The process according to claim 12 , wherein the beta 2 -adrenergic agonist is a maleate salt of indacaterol.

39 . The process according to claim 38 , wherein the fluorinated model propellant is 2H,3H-perfluoropentane (HPFP).

40 . The process according to claim 38 , wherein:
the C14-C20 saturated fatty acid is myristic acid; and the myristic acid is present in an amount of 1.0 to 2.0% by weight based on the total weight of the crystalline microparticles.

41 . The process according to claim 38 , further comprising:
preparing a pharmaceutical aerosol formulation comprising the coated microparticles in suspension in a liquefied propellant gas; and filling the pharmaceutical aerosol formulation into a pressurized metered dose inhaler.

42 . The process according to claim 41 , wherein the liquefied propellant gas is 1,1,1,2,3,3,3-heptafluoro-n-propane (HFA227) or 1,1,1,2-tetrafluoroethane (HFA 134a), or a mixture thereof.

43 . The process according to claim 41 , wherein the formulation, upon storage, meets the requirements of EMEA Guideline CPMP/QWP/122/02.

44 . The process according to claim 38 , further comprising preparing a dry powder pharmaceutical formulation comprising the coated microparticles.

Assignees

• Chiesi Farm Spa

Inventors

• Brambilla Gaetano
• Colombo Paolo
• Buttini Francesca
• Miozzi Michele

Classifications

• A61P11/08

  Bronchodilators · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• B01J2/02

  by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops · CPC title

• A61K9/5015 Primary

  Organic compounds, e.g. fats, sugars · CPC title