Stable particle formulations of erythropoietin receptor agonists

• US 20060029551A1
• Filed: 08/01/2005
• Published: 02/09/2006
• Est. Priority Date: 08/05/2004
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Liu, Kui, Desjardin, Michael A.
• Application Number:
  US11/194,889
• Publication Number:
  US 20060029551A1
• Time in Patent Office: Days
• US Class Current: 424/46
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/19 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 Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 Antianaemics

Abstract

A particle formulation includes an erythropoietin receptor agonist, a buffer, and a sugar, wherein the buffer and sugar stabilize the erythropoietin receptor agonist against aggregation.

Claims

1. A particle formulation comprising:

an erythropoietin receptor agonist;

a buffer; and

a sugar;

wherein the buffer and sugar stabilize the erythropoietin receptor agonist against aggregation.

2. The particle formulation of claim 1, which is stable at 40°

C. for at least 1 month.

3. The particle formulation of claim 1, which is stable at 37°

C. for at least 3 months.

4. The particle formulation of claim 1, which is lyophilized or spray-dried.

5. The particle formulation of claim 1, wherein the erythropoietin receptor agonist is present in an amount ranging from 0.1 to 99.9% by weight.

6. The particle formulation of claim 1, wherein the erythropoietin receptor agonist is present in an amount ranging from 0.1 to 30% by weight.

7. The particle formulation of claim 1, wherein the erythropoietin receptor agonist is erythropoietin.

8. The particle formulation of claim 1, wherein the sugar is sucrose and the buffer is citrate or histidine.

9. The particle formulation of claim 1, wherein the sugar is sucrose, the buffer is citrate, and the weight ratio of sugar to erythropoietin receptor agonist is greater than 2.0.

10. The particle formulation of claim 1, wherein the buffer has a pH value in a range from 5.0 to 8.0.

11. The particle formulation of claim 1, wherein the buffer has a pH value in a range from 5.5 to 7.5.

12. The particle formulation of claim 1, wherein the buffer is present in an amount ranging from 0.1 to 99.8% by weight.

13. The particle formulation of claim 1, further comprising a surfactant in an amount up to 10% by weight.

14. The particle formulation of claim 1, further comprising one or more components selected from the group consisting of surfactants, bulking agents, and salts.

15. The particle formulation of claim 1, further comprising a stabilizing component selected from the group consisting of amino acids, polyols, and polymers.

16. The particle formulation of claim 1, which has a total soluble aggregate less than 3% over 3 months at 37°

C.

17. The particle formulation of claim 1, which has dimer less than 3% over 3 months at 40°

C.

18. A particle formulation comprising:

an erythropoietin receptor agonist;

a buffer selected from the group consisting of citrate and histidine; and

a sugar;

wherein the particle formulation has a total soluble aggregate less than 3% over 1 month at 40°

C.

19. The particle formulation of claim 18, wherein the sugar is sucrose.

20. The particle formulation of claim 18, further comprising a surfactant in an amount up to 10% by weight.