SUSPENSION FORMULATIONS

• US 20110182997A1
• Filed: 02/02/2009
• Published: 07/28/2011
• Est. Priority Date: 02/01/2008
• Status: Active Grant

• Current Assignee: Innovata Biomed Limited (Vectura Group Ltd.), Vectura Limited (Vectura Group Ltd.)
• Original Assignee: Innovata Biomed Limited (Vectura Group Ltd.), Vectura Limited (Vectura Group Ltd.)
• Inventors: Lewis, David Andrew, Whitfield, Nicola Kim, Church, Tanya, Keeble, Christina Alexandra
• Granted Patent: US 9,011,923 B2
• Time in Patent Office: Days
• US Class Current: 424/490
• 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 31/00 Medicinal preparations containing organic active ingredients
• 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 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: 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
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators

Abstract

The present invention relates to suspension formulations, especially those for delivering a pharmaceutically active agent in aerosol form using a spray or aerosol device, such as a pressurised metered dose inhaler (pMDI). The formulations may be for pulmonary, nasal, buccal or topical administration, but are preferably for pulmonary inhalation.

Claims

1. A suspension formulation comprising particles comprising a pharmaceutically active agent and a propellant, the formulation further comprising one or more suspension stabilisers.

2. A suspension formulation as claimed in claim 1, wherein the suspension stabiliser is coated on the particles of pharmaceutically active agent.

3. A suspension formulation as claimed in claim 1, wherein the suspension stabiliser is incorporated into the particles of pharmaceutically active agent.

4. A suspension formulation as claimed in claim 1, wherein the suspension stabiliser allows the active agent to retain its physical state.

5. A suspension formulation as claimed in claim 4, wherein the amorphous state of the active agent is retained.

6. A suspension formulation as claimed in claim 1, wherein the suspension stabiliser is an amino acid.

7. A suspension formulation as claimed in claim 6, wherein the suspension stabiliser is leucine.

8. A suspension formulation as claimed in claim 1, wherein the suspension stabiliser is a saccharide, preferably a disaccharide.

9. A suspension formulation as claimed in claim 8, wherein the suspension stabiliser is trehalose.

10. A suspension formulation as claimed in claim 1, further comprising a co-solvent in an amount which does not substantially enhance the solubility of the active agent in the formulation.

22. A suspension formulation as claimed in claim 10, wherein the co-solvent is ethanol.

23. A suspension formulation as claimed in claim 22, wherein the ethanol is present in an amount of less than 1% w/w based upon the total formulation.

24. A suspension formulation as claimed in claim 1, wherein the particles of active agent are formed by spray drying.

25. A suspension formulation as claimed in claim 24, wherein the particles of active agent are formed by co-spray drying the active agent and the suspension stabiliser.

26. A suspension formulation as claimed in claim 1, wherein the propellant comprises HFA 227, HFA 134a or a combination thereof.

27. A suspension formulation as claimed in claim 1, further comprising one or more of surfactants, lubricants, flavouring agents and additives.

28. A method for preparing a suspension formulation as claimed in claim 1, wherein the method includes forming the active particles by spray drying and adding the spray dried particles to the propellant.

29. A method as claimed in claim 28, wherein the active agent is co-spray dried with one or more suspension stabilisers.

30. A method as claimed in claim 28, wherein one or more suspension stabilisers are coated on the surfaces of the spray dried active particles by a milling step.

11. A suspension formulation comprising particles comprising a pharmaceutically active agent and a propellant, the formulation further comprising a co-solvent in an amount which does not substantially enhance the solubility of the active agent in the formulation.

12. A suspension formulation as claimed in claim 11, further comprising one or more suspension stabilisers.

13. A suspension formulation as claimed in claim 11, wherein the co-solvent is ethanol.

14. A suspension formulation as claimed in claim 13, wherein the ethanol is present in an amount of less than 1% w/w based upon the total formulation.

15. A suspension formulation as claimed in claim 11, wherein the particles of active agent are formed by spray drying.

16. A suspension formulation as claimed in claim 15, wherein the formulation comprises one or more suspension stabilisers and the particles of active agent are formed by co-spray drying the active agent and the suspension stabiliser.

17. A suspension formulation as claimed in claim 11, wherein the propellant comprises HFA 227, HFA 134a or a combination thereof.

18. A suspension formulation as claimed in claim 11, further comprising one or more of surfactants, lubricants, flavouring agents and additives.

19. A method for preparing a suspension formulation as claimed in claim 11, wherein the method includes forming the active particles by spray drying and adding the spray dried particles to the propellant.

20. A method as claimed in claim 19, wherein the active agent is co-spray dried with one or more suspension stabilisers.

21. A method as claimed in claim 19, wherein one or more suspension stabilisers are coated on the surfaces of the spray dried active particles by a milling step.