Formation of stable submicron peptide or protein particles by thin film freezing

Patent metadata

Field	Value
Publication number	US-10285945-B2
Application number	US-201715479137-A
Country	US
Kind code	B2
Filing date	Apr 4, 2017
Priority date	Jun 22, 2007
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

The present invention includes compositions and methods for preparing micron-sized or submicron-sized particles by dissolving a water soluble effective ingredient in one or more solvents; spraying or dripping droplets solvent such that the effective ingredient is exposed to a vapor-liquid interface of less than 50, 100, 150, 200, 250, 200, 400 or 500 cm −1 area/volume to, e.g., increase protein stability; and contacting the droplet with a freezing surface that has a temperature differential of at least 30° C. between the droplet and the surface, wherein the surface freezes the droplet into a thin film with a thickness of less than 500 micrometers and a surface area to volume between 25 to 500 cm −1 .

First claim

What is claimed is:

1. A freezing surface comprising a frozen drug composition layered on the surface, the drug composition comprising a proteinaceous pharmaceutical agent wherein the layer has a thickness of less than 500 micrometers and a surface area to volume of from 25 to 500 cm −1 .

2. The surface of claim 1 , formed by a process comprising dissolving the agent in one or more solvents;
spraying or dripping droplets of said dissolved pharmaceutical agent such that the pharmaceutical agent is exposed to a vapor-liquid interface of less than 500 cm −1 area/volume; and
contacting the droplets with a freezing surface that has a temperature differential of at least 30° C. between the droplets and the surface, wherein the surface freezes the droplets into a film with a thickness of less than 500 micrometers and a surface area to volume between 25 to 500 cm −1 , to thereby form the freezing surface comprising a frozen drug composition layered on the surface.

3. The surface of claim 2 , wherein the solvent is selected from the group consisting of ethanol, methanol, tetrahydrofuran, acetonitrile, acetone, tert-butyl alcohol, dimethyl sulfoxide, N,N-dimethyl formamide, diethyl ether, methylene chloride, ethyl acetate, isopropyl acetate, butyl acetate, propyl acetate, toluene, hexanes, heptane, pentane, and combinations thereof.

4. The surface of claim 2 , further comprising the step of removing the solvent from the frozen material to form micron or submicron sized particles.

5. The surface of claim 2 , wherein the droplets freeze upon contact with the surface in about 50, 75, 100, 125, 150, 175, 200, 250, 500, 1,000 and 2,000 milliseconds.

6. The surface of claim 2 , wherein the droplets freeze upon contact with the surface in 50, 150, or 500 milliseconds.

7. The surface of claim 2 , wherein the droplet has a diameter between 0.1 and 5 mm at room temperature.

8. The method of claim 2 , wherein the droplet has a diameter between 2 and 4 mm at room temperature.

9. The surface of claim 1 , wherein the solid surface is made of glass or metal.

10. The surface of claim 1 , wherein the solid surface is a roller, a platter, a plate, a platen surface, a conveyor surface, a flat surface, a circular surface, a cylindrical surface, a conical surface or an oval surface.

11. The surface of claim 1 or 2 , wherein solvent present has been removed and the drug composition is in the form of micron or submicron sized particles.

12. The surface of claim 11 , wherein the particles have a surface area per unit weight of 10, 15, 25, 50, 75, 100, 125, 150 or 200 m 2 /gram.

13. The surface of claim 1 , wherein the particle has less than 50% of the peptide or protein at the particle surface.

14. The surface of claim 1 , wherein the proteinaceous pharmaceutical is an enzyme.

15. The surface of claim 1 , wherein the proteinaceous pharmaceutical is a polypeptide.

16. The surface of claim 1 , wherein the proteinaceous pharmaceutical is water soluble.

Assignees

• Univ Texas

Inventors

• Johnston Keith P
• Engstrom Joshua
• Williams Iii Robert O

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P25/34

  Tobacco-abuse · CPC title