Lyophilisation targeting defined residual moisture by limited desorption energy levels

• US 8,769,841 B2
• Filed: 09/24/2012
• Issued: 07/08/2014
• Est. Priority Date: 06/20/2006
• Status: Expired due to Fees

• Current Assignee: Octapharma AG (Octapharma Nordic AB)
• Original Assignee: Octapharma AG (Octapharma Nordic AB)
• Inventors: Gruber, Gerhard, Reschny, Anton
• Primary Examiner(s): Gravini, Steve M
• Application Number:
  US13/625,482
• Publication Number:
  US 20130118025A1
• Time in Patent Office: 652 Days
• Field of Search: 342/84, 342/87, 34/92, 435/6, 435/69.1, 435/199, 435/252.3, 424/185.1, 424/142.1, 530/330, 530/388.15, 560/322, 536/23.1
• US Class Current: 34/287
• 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: F26B 5/06 the process involving freezing

Abstract

A process of freeze drying of an essentially aqueous solution comprising at least one first step having a first temperature and pressure level (i.e. primary drying phase) and at least one second step having a second temperature and pressure level (i.e. secondary drying phase) following the first step, wherein in the secondary drying phase limited desorption energy input is applied.

Claims

1. A process of freeze drying an essentially aqueous solution comprising the sequential steps of

a) subjecting the solution to a primary drying phase at a first temperature and pressure level to obtain a product;

and

b) subjecting the product to a secondary drying phase at 0.01 mbar and a temperature range from −

5°

C. to +3°

C. for at least 3 hours;

wherein a limited desorption energy input is applied in the secondary drying phase;

to obtain a lyophilized product having a predefined target rest moisture in steady-state conditions of 0.79-1.14%.

2. The process of claim 1 wherein the limited desorption energy input applied results in a desorption rate at the target rest moisture of the product approaching zero.

3. The process of claim 1 having a first shelf temperature level and a first chamber pressure level (primary or sublimation drying phase) and at least one second step having a second shelf temperature level and a second chamber pressure level (secondary or desorption drying phase) following the first step, characterized in that in the secondary desorption drying phase at which the desorption rate at the target at rest moisture of the product approaches zero.

4. The process of claim 1, wherein the aqueous solution contains biopolymers such as proteins, polysaccharides, nucleic acids.

5. The process of claim 1, wherein the biopolymers are pharmaceutically active substances.

6. The process of claim 1, wherein the aqueous solution contains proteins selected from the group consisting of plasma proteins such as blood plasma, coagulation factors, proteases or cofactors, protease inhibitors, immunoglobulins, albumin and mixtures thereof.

7. The process of claim 1, wherein the aqueous solution contains proteins selected from the group consisting of one or more growth factors, hormones, cytokines and mixtures thereof.

8. The process of claim 1, wherein the aqueous solution contains recombinantly or transgenically produced proteins.

9. The process of claim 1, wherein the aqueous solution contains prior to drying additionally buffer substances.