METHOD AND DEVICE FOR OPTIMIZED FREEZE-DRYING OF A PHARMACEUTICAL PRODUCT

• US 20180023893A1
• Filed: 02/04/2016
• Published: 01/25/2018
• Est. Priority Date: 02/04/2015
• Status: Active Grant

• Current Assignee: ProJect Pharmaceutics GmbH
• Original Assignee: ProJect Pharmaceutics GmbH
• Inventors: SCHUETZ, Andreas
• Granted Patent: US 10,809,002 B2
• Time in Patent Office: Days
• CPC Class Codes: B65B 3/003 Filling medical containers such as ampoules, vials, syringes or the like
• CPC Class Codes: B65B 31/027 closed by a stopper
• CPC Class Codes: B65B 7/2821 applying plugs or threadless stoppers for bottles or jars B67B1/04
• CPC Class Codes: B65D 25/108 Devices, e.g. plates, presenting apertures through which the articles project
• CPC Class Codes: B65D 51/241 provided with freeze-drying means
• CPC Class Codes: F26B 25/16 mainly closed, e.g. drum
• CPC Class Codes: F26B 5/06 the process involving freezing
• CPC Class Codes: F26B 9/066 the products to be dried being disposed on one or more containers, which may have at least partly gas-previous walls, e.g. trays or shelves in a stack F26B9/003 takes precedence; in combination with duct systems F26B21/00

Abstract

A method for lyophilizing a substance is provided which may include placing at least one vial containing the substance in a lyophilization chamber, the at least one vial having an opening in which a stopper is inserted in a closed state not allowing gas exchange between the interior and exterior of the vial; providing mechanical means external to the stopper and arranged at the opening for restricting an upward movement of the stopper; lowering the temperature within the lyophilization chamber to a predefined value below the freezing temperature of the substance and reducing the pressure within the lyophilization chamber to a predefined pressure at a predefined temperature, the predefined pressure being chosen such that the force exerted by it on the stopper lifts the stopper from the closed state to an exchange state in which the stopper is only partly inserted in the opening of the vial allowing gas exchange between the interior and exterior of the vial, wherein the lowering of the temperature within the lyophilization chamber to the predefined value is performed before reducing the pressure within the lyophilization chamber to the predefined pressure and wherein lifting the stopper from the closed state abruptly lowers the pressure within the at least one vial which initiates nucleation in the substance within that vial. In addition, mechanical means is provided which may be used in order to perform the method for lyophilizing a substance.

Claims

1. A method for lyophilizing a substance comprising the steps of:

placing at least one vial containing the substance in a lyophilization chamber, the at least one vial having an opening in which a stopper is inserted in a closed state in which the stopper does not allow gas exchange between the interior and exterior of the vial;

providing mechanical means external to the stopper and arranged at the opening for restricting an upward movement of the stopper;

lowering the temperature within the lyophilization chamber to a predefined value below the freezing temperature of the substance; and

reducing the pressure within the lyophilization chamber to a predefined pressure, the predefined pressure being chosen such that the force exerted by it on the stopper lifts the stopper from the closed state to an exchange state in which the stopper is only partly inserted in the opening of the vial allowing gas exchange between the interior and exterior of the vial;

wherein the lowering of the temperature within the lyophilization chamber to the predefined value is performed before reducing the pressure within the lyophilization chamber to the predefined pressure; and

wherein lifting the stopper from the closed state abruptly lowers the pressure within the at least one vial which initiates nucleation in the substance within that vial.

2. The method for lyophilizing according to claim 1,

wherein the mechanical means define a maximum portion of the stopper which can protrude outwardly from the opening of the vial in the exchange state.

3. The method for lyophilizing according to claim 1,

wherein the external mechanical means are configured to prevent the stopper from falling off the opening of the at least one vial when the stopper is lifted from the closed state.

4. The method for lyophilizing according to any one of claim 1,

wherein providing the mechanical means external to the stopper for restricting the upward movement of the stopper includes positioning of shelves within the lyophilization chamber at a predefined distance from each other.

5. The method for lyophilizing according to claim 1,

wherein providing the mechanical means external to the stopper for restricting the upward movement of the stopper includes providing a closure device on a neck of the vial which encloses a space above the opening of the vial thereby being configured to restrict the upward travel of the stopper when it is lifted from the closed state into the exchange state.

6. The method for lyophilizing according to claim 5, further comprising the step of:

forcing the stopper into and securing it in the closed state after the lyophilization process by pressing the closure device onto the neck of the vial.

7. The method for lyophilizing according to claim 1,

wherein providing the mechanical means external to the stopper for restricting the upward movement of the stopper includes placing the at least one vial into the lyophilization chamber in a tray package having a container and a lid, the lid being held at a predefined distance from the container by dynamic elements, the lid being configured to restrict the upward travel of the stopper when it transitions from the closed state into the exchange state.

8. The method for lyophilizing according to claim 1,

wherein the predefined pressure corresponds to a pressure value of 800 mbar or less.

9. A tray package for holding and storing vials, comprising:

a container;

a holding element positioned within the container and having at least one opening therein for holding a vial; and

a lid movably supported at a predefined distance from the container.

10. The tray package of claim 9,

wherein the lid is movable in a downward direction from its quiescent position in a reversible manner.

11. The tray package of claim 9, further comprising:

at least one guiding element which is configured to restrict motion of the lid with respect to the container to a uniaxial motion.