Use of polymeric excipients for lyophilization or freezing of particles

Patent metadata

Field	Value
Publication number	US-9585960-B2
Application number	US-201214362382-A
Country	US
Kind code	B2
Filing date	Dec 13, 2012
Priority date	Dec 14, 2011
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

Abstract

Provided herein are use of polymeric excipients, specifically polyvinyl alcohols, optionally in conjunction with sugars, as cryoprotectants to prevent aggregation of PEG-containing particles. Also provided are PEG-containing particles comprising such polymeric excipients.

First claim

What is claimed is:

1. A method of preparing a lyophilized or frozen preparation of a composition comprising solid particles comprising a drug, wherein the solid particles are coated with polyethylene glycol (PEG), the method comprising adding polyvinyl alcohol (PVA) to an aqueous composition comprising the solid particles and lyophilizing or freezing the aqueous composition, wherein the polyvinyl alcohol is about 13K to about 31K.

2. A method of preventing particle aggregation and/or particle size increase upon lyophilization and resuspension or freezing and thawing of an aqueous composition comprising solid particles comprising a drug, wherein the solid particles are coated with polyethylene glycol (PEG), the method comprising adding polyvinyl alcohol (PVA) to the aqueous solid particle composition prior to lyophilization or freezing and lyophilizing or freezing the aqueous composition, wherein the polyvinyl alcohol is about 13K to about 31K.

3. The method of claim 1 , wherein the concentration of polyvinyl alcohol in the aqueous solid particle composition is between about 0.05% (w/v) to about 1% (w/v).

4. The method of claim 1 , wherein the polyvinyl alcohol is at least about 50% hydrolyzed.

5. The method of claim 1 , wherein the weight ratio of the polyvinyl alcohol to the solid particles in the resultant composition is less than about 0.2:1.

6. The method of claim 1 , wherein the concentration of the solid particles in the aqueous solid particle composition is about 1% to about 25% (w/v).

7. The method of claim 1 , wherein the solid particles comprise a polymeric core matrix coated with polyethylene glycol.

8. The method of claim 1 , wherein the solid particles comprise PLA or PLGA.

9. The method of claim 1 , wherein the average particle size of the solid particles in the solid particle composition is no greater than about 200 nm.

10. The method of claim 1 , further comprising adding a sugar to the aqueous solid particle composition prior to lyophilization or freezing.

11. The method of claim 1 , wherein the aqueous solid particle composition to which the polyvinyl alcohol is added is free of polyvinyl alcohol.

12. The method of claim 1 , wherein the polyethylene glycol is covalently attached to the surface of the solid particles or tethered to the surface of the solid particles by hydrophobic or charge interactions.

13. The method of claim 1 , wherein the polyethylene glycol is one of the structural components of the solid particles.

14. A pharmaceutical composition comprising solid particles comprising a drug, wherein the solid particles are coated with polyethylene glycol (PEG), wherein the composition further comprises polyvinyl alcohol (PVA), and wherein less than about 2% of the total polyvinyl alcohol in the pharmaceutical composition is associated with the solid particles, wherein the polyvinyl alcohol is about 13K to about 31K, and wherein the pharmaceutical composition is lyophilized or frozen.

15. The pharmaceutical composition of claim 14 , wherein the concentration of polyvinyl alcohol in the solid particle composition is between about 0.05% to about 1%.

16. The pharmaceutical composition of claim 14 , wherein the polyvinyl alcohol is at least about 50% hydrolyzed.

17. The pharmaceutical composition of claim 14 , wherein the solid particles comprise a polymeric matrix core coated with polyethylene glycol.

18. The pharmaceutical composition of claim 14 , wherein the average particle size of the solid particles in the solid particle composition is no greater than about 200 nm.

19. A pharmaceutical composition produced by the method of claim 1 .

20. Use of the pharmaceutical composition of claim 19 for the treatment of a disease.

Assignees

• Abraxis Bioscience Llc

Inventors

• Foss Willard
• Shinde Rajesh

Classifications

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K9/5123

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

• A61K9/19 Primary

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61P35/00

  Antineoplastic agents · CPC title