Storage stable powder compositions of interleukin-4 receptor
View Patent ↗The present invention provides storage stable dry powder compositions of IL-4R. The powder compositions demonstrate superior chemical and physical stability over their solution counterparts, particularly upon storage under varying conditions of temperature and humidity. Moreover, the powders, as prepared, possess good aerosol properties, which are maintained upon storage.
1. A method for aerosolizing a soluble interleukin-4 receptor (1L-4R) dry powder composition, said method comprising:
(a) providing an 1L-4R dry powder composition comprised of an active agent and one or more excipients, wherein (i) the active agent consists essentially of soluble interleukin-4 receptor, (ii) the one or more excipients are selected from the group consisting of carbohydrates, lipids, divalent metal cation, buffers, amino acids, oligopeptides, peptides, and proteins, and (iii) the composition comprises particles having a mass median aerodynamic diameter (MMAD) of less than about 10 micros; and
(b) dispersing said composition into a gas stream to form an aerosolized dry powder suitable for inhalation.
2. The method of claim 1 , wherein said dispersing is achieved by means of a dry powder inhaler.
3. The method of claim 1 , wherein the dry powder composition comprises spray-dried particles comprised of IL-4R.
4. The method of claim 1 , wherein the dry powder composition is characterized by a decrease in monomer content of not more than 10% when determined after storage of said composition for 14 days at 33% relative humidity.
5. The method of claim 1 , wherein the dry powder composition is characterized by formation of less than 10% insoluble aggregates in water after storage for 14 days at 33% relative humidity.
6. The method of claim 1 , wherein the dry powder composition is characterized as being temperature stable, exhibiting a minimal increase in aggregate formation and a minimal change in monomer content, as compared to the level of aggregate and monomer content of its pre-spray dried solutions or suspension, under extreme temperatures.
7. The method of claim 1 , wherein one of the one or more excipients is a carbohydrate.
8. The method of claim 7 , wherein the carbohydrate is a sugar or sugar alcohol.
9. The method of claim 1 , wherein one of the one or more excipients is an amino acid.
10. The method of claim 9 , wherein the amino acid is a hydrophobic amino acid.
11. The method of claim 1 , wherein one of the one or more excipients is selected from the group consisting of citrate salts, leucine, raffinose, zinc salts, and combinations thereof.
12. The method of claim 1 , wherein one of the one or more excipients is a buffer.
13. The method of claim 1 , wherein one of the one or more excipients is a divalent metal cation.
14. The method of claim 1 , wherein the dry powder composition is characterized by an emitted dose of at least 30%.
15. The method of claim 14 , wherein the dry powder composition is characterized by an emitted dose of at least 45%.
16. The method of claim 15 , wherein the dry powder composition is characterized by an emitted dose of at least 60%.
17. The method of claim 1 , wherein the dry powder composition is comprised of particles having a mass median aerodynamic diameter (MMAD) of less than about 5 microns.
18. The method of claim 17 , wherein the dry powder composition is comprised of particles having a mass median aerodynamic diameter (MMAD) of less than about 3.5 microns.
19. The method of claim 18 , wherein the dry powder composition is comprised of particles having a mass median diameter (MMAD) of between about 0.1 to 3 microns.
20. The method of claim 1 , wherein the dry powder composition is characterized by a residual moisture content is less than about 10% by weight.
21. The method of claim 20 , wherein the dry powder composition is characterized by a residual moisture content of less than about 5% by weight.
22. The method of claim 1 , wherein the dry powder composition is characterized by a bulk density ranging from about 0.1–10 g/cc.