Inhalation compositions comprising glucose anhydrous

• US 10,111,957 B2
• Filed: 06/27/2013
• Issued: 10/30/2018
• Est. Priority Date: 07/05/2012
• Status: Active Grant

• Current Assignee: Arven Ilac San. ve Tic. A.S.
• Original Assignee: Sanovel Ilac Sanayi Ve Ticaret A S
• Inventors: Cifter, Umit, Turkyilmaz, Ali, Mutlu, Onur
• Primary Examiner(s): Crow, Robert T.
• Assistant Examiner(s): Nguyen, John P
• Application Number:
  US14/412,609
• Publication Number:
  US 20150165036A1
• Time in Patent Office: 1,951 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/4704 2-Quinolinones, e.g. carbostyril
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51

Abstract

The invention relates to pharmaceutical powder compositions administered by means of inhalers. More particularly, it relates to pharmaceutical powder compositions having the content uniformity and the desired stability used in inhaler devices.

Claims

1. A dry powder inhalation composition comprising,

at least one corticosteroid or a pharmaceutically acceptable salt thereof,

fine particle lactose in an amount of 1-20% by weight of said composition and having d50 particle size in the range of 4-10 μ

m and coarse particle anhydrous glucose in an amount of 80-99% by weight of said composition and having a d50 particle size in the range of 50-120 μ

m.

2. The pharmaceutical composition according to claim 1, wherein the d50 particle size of said fine particle lactose is 4-7 μ

m.

3. The pharmaceutical composition according to claim 1, wherein a d50 particle size of said coarse particle anhydrous glucose is 50-75 μ

m.

4. The pharmaceutical composition according to claim 1, further comprising coarse particle lactose with a d50 particle size of 50-80 μ

m or of 50-75 μ

m, coarse particle lactose with a d10 particle size of 10-50 μ

m, and/or coarse particle lactose with a d90 particle size of 120-300 μ

m or 75-250 μ

m.

5. The pharmaceutical composition according to claim 1, further comprising fine particle anhydrous glucose with a d50 particle size of 4-7 μ

m, fine particle anhydrous glucose with a d10 particle size of 1-5 μ

m or 1-4 μ

m; and

/or fine particle anhydrous glucose with a d90 particle size of 10-20 μ

m or 7-10 μ

m.

6. The pharmaceutical composition according to claim 1, wherein the amount of said lactose is in the range of 1-15%, or 1-10%, by weight.

7. The pharmaceutical composition according to claim 1, wherein the amount of said anhydrous glucose is in the range of 85-99%, or 90-99%, by weight of the composition.

8. The pharmaceutical composition according to claim 1, wherein, said corticosteroid is selected from the group consisting of at least one or a mixture of ciclesonide, budesonide, fluticasone, aldosterone, beclomethasone, betametazone, chloprednol, cortisone, cortivasol, deoxycortone, desonide, desoxymethasone, dexamethasone, difluocortolone, fluchloralin, flumetasone, flunisolide, fluocinolone, fluocinonide, flurocortisone, fluocortolone, flurometolone, flurandrenolone, halcinonide, hydrocortisone, icometasone, meprednisone, methylprednisolone, mometasone, paramethasone, prednisolone, prednisone, tixocortole, and/or triamcinolone.

9. The pharmaceutical composition according to claim 8, wherein, said corticosteroid is selected from the group consisting of ciclesonide, budesonide, fluticasone, and mometasone.

10. The pharmaceutical composition according to claim 1, further comprising (a) one or more β

2-adrenergic agonists;

(b) one or more muscarinic receptor antagonists;

or (c) one or more β

2-adrenergic agonists and one or more muscarinic receptor antagonists.

11. The pharmaceutical composition according to claim 10, wherein, said muscarinic receptor antagonist is selected from the group consisting of at least one or a mixture of tiotropium, glycopyronium, aclidinium, darotropium, and ipratropium.

12. The pharmaceutical composition according to claim 10, wherein, said beta-2 adrenergic agonist is selected from the group consisting of at least one or a mixture of salmeterol, formoterol, arformoterol, salbutamol, indacaterol, terbutaline, metaproterenol, vilanterol, carmoterol, olodaterol, bambuterol, and clenbuterol.

13. The pharmaceutical composition according to claim 1, further comprising at least one excipient selected from the group consisting of glucose, mannitol, sorbitol, trehalose, and cellobiose.

14. The pharmaceutical composition according to claim 1, wherein, said composition comprises one of the following therapeutically active combinations:

i. Budesonide and indacaterol,

ii. Budesonide and oladaterol,

iii. Budesonide and vilanterol,

iv. Budesonide and salmeterol,

v. Budesonide and formoterol,

vi. Budesonide and carmoterol,

vii. Budesonide and arformoterol,

viii. fluticasone and formoterol,

ix. fluticasone and salmeterol,

x. fluticasone and vilanterol,

xi. fluticasone and indacaterol,

xii. fluticasone and olodaterol,

xiii. fluticasone and carmoterol,

xiv. fluticasone and arformoterol,

xv. fluticasone and salbutamol,

xvi. mometasone and formoterol,

xvii. mometasone and indacaterol,

xviii. mometasone and vilanterol,

xix. mometasone and olodaterol,

xx. mometasone and carmoterol,

xxi. mometasone and arformoterol,

xxii. mometasone and salmeterol,

xxiii. ciclesonide and formoterol,

xxiv. ciclesonide and vilanterol,

xxv. ciclesonide and indacaterol,

xxvi. ciclesonide and olodaterol,

xxvii. ciclesonide and carmoterol,

xxviii. ciclesonide and arformoterol,

xxix. ciclesonide and salmeterol,

xxx. budesonide and tiotropium,

xxxi. fluticasone and tiotropium,

xxxii. mometason and tiotropium,

xxxiii. ciclesonide and tiotropium,

xxxiv. budesonide, formoterol and tiotropium,

xxxv. budesonide, salmeterol and tiotropium,

xxxvi. budesonide, arformoterol and tiotropium,

xxxvii. budesonide, carmoterol and tiotropium,

xxxviii. ciclesonide, formoterol and tiotropium,

xxxix. ciclesonide, salmeterol and tiotropium,

xl. ciclesonide, carmoterol and tiotropium,

xli. ciclesonide, arformoterol and tiotropium,

xlii. ciclesonide, indacaterol and tiotropium,

xliii. ciclesonide, olodaterol and tiotropium,

xliv. ciclesonide, vilanterol and tiotropium,

xlv. fluticasone, salmeterol and tiotropium,

xlvi. fluticasone, formoterol and tiotropium,

xlvii. fluticasone, arfomoterol and tiotropium,

xlviii. fluticasone, carmoterol and tiotropium,

xlix. fluticasone, vilanterol and tiotropium,

l. fluticasone, olodaterol and tiotropium,

li. fluticasone, indacaterol and tiotropium,

lii. budesonide, indacaterol and tiotropium,

liii. budesonide, olodaterol and tiotropium,

liv. budesonide, vilanterol and tiotropium,

lv. mometasone, salmeterol and tiotropium,

lvi. mometasone, formoterol and tiotropium,

lvii. mometasone, indacaterol and tiotropium,

lviii. mometasone, vilanterol and tiotropium,

lix. mometasone, oladaterol and tiotropium,

lx. mometasone, arformoterol and tiotropium,

lxi. mometasone, indacaterol and glycopyrronium,

lxii. mometasone, salmeterol and glycopyrronium,

lxiii. mometasone, formoterol and glycopyrronium,

lxiv. mometasone, carmoterol and glycopyrronium,

lxv. mometasone, olodaterol and glycopyrronium,

lxvi. mometasone, vilanterol and glycopyrronium,

lxvii. fluticasone, salmeterol and salbutamol, and

lxviii. fluticasone, arformeterol and salbutamol.

15. The pharmaceutical composition according to claim 1, wherein said composition is in a blister having air and moisture barrier property, enabling simultaneous, respective and synchronic application.

16. The pharmaceutical composition according to claim 1, wherein said composition is in a blister in a dry powder inhaler device suitable for simultaneous, respective and synchronic application, wherein the inhaler device has at least one locking mechanism ensuring the device to be maintained locked in both of the positions in which the inhaler device is ready for inhalation and the lid of the inhaler device is closed and ensuring the device to be automatically re-set once the lid is closed.

17. The pharmaceutical composition according to claim 1, wherein, said composition comprises a dry powder inhaler device suitable for simultaneous, respective and synchronic application in a capsule.

18. The pharmaceutical composition according to claim 1, wherein the coarse particle anhydrous glucose has a ratio of the d50 particle size/d90 particle size equal to 0.40 or greater.

19. The pharmaceutical composition according to claim 1, wherein the coarse particle anhydrous glucose has a ratio of the d50 particle size/d90 particle size between 0.45 and 0.50.

20. The pharmaceutical composition according to claim 1, wherein the coarse particle anhydrous glucose has a ratio of the d50 particle size/d90 particle size between 0.50 and 0.70.

21. The pharmaceutical composition according to claim 18, wherein the coarse particle anhydrous glucose comprises spray-dried anhydrous glucose.

22. The pharmaceutical composition according to claim 19, wherein the coarse particle anhydrous glucose comprises spray-dried anhydrous glucose.

23. The pharmaceutical composition according to claim 20, wherein the coarse particle anhydrous glucose comprises spray-dried anhydrous glucose.

24. The pharmaceutical composition according to claim 3, wherein the coarse particle anhydrous glucose has a ratio of the d50 particle size/d90 particle size equal to 0.40 or greater.

25. The pharmaceutical composition according to claim 3, wherein the coarse particle anhydrous glucose has a ratio of the d50 particle size/d90 particle size between 0.45 and 0.50.

26. The pharmaceutical composition according to claim 3, wherein the coarse particle anhydrous glucose has a ratio of the d50 particle size/d90 particle size between 0.50 and 0.70.

27. The pharmaceutical composition according to claim 1, wherein said fine particle lactose has a d10 particle size of 1-5 μ

m.

28. The pharmaceutical composition according to claim 1, wherein said fine particle lactose has a d90 particle size of 7-20 μ

m.

29. The pharmaceutical composition according to claim 1, wherein said coarse particle anhydrous glucose has a d10 particle size of 10-50 μ

m.

30. The pharmaceutical composition according to claim 1, wherein said coarse particle anhydrous glucose has a d90 particle size of 120-300 μ

m.

31. The pharmaceutical composition according to claim 27, wherein said fine particle lactose has a d10 particle size of 1-4 μ

m.

32. The pharmaceutical composition according to claim 28, wherein said fine particle lactose has a d90 particle size of 7-15 μ

m.

33. The pharmaceutical composition according to claim 30, wherein said coarse particle anhydrous glucose has a d90 particle size of 75-250 μ

m.

34. The pharmaceutical composition according to claim 29, wherein said coarse particle anhydrous glucose has a d90 particle size of 75-250 μ

m.