Method of microwave vacuum drying spherical-shaped pellets of biological materials

Patent metadata

Field	Value
Publication number	US-10429129-B2
Application number	US-201415029062-A
Country	US
Kind code	B2
Filing date	Oct 13, 2014
Priority date	Oct 16, 2013
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

Methods for preparing dried pellets of biological materials are described. The pellets can have a substantially spherical shape and are prepared by freezing droplets of a liquid composition of a desired biological material on a solid surface followed by microwave vacuum drying the frozen droplets. These methods are useful for preparing dried pellets having a high concentration of a desired biological material, in particular a therapeutic protein or vaccine, and which have a faster reconstitution time than lyophilized powder cakes prepared in vials.

First claim

What is claimed is:

1. A method of preparing a dried pellet of an enveloped live virus, comprising:
a) dispensing an aliquot of a liquid composition comprising the enveloped live virus as a single droplet onto a solid surface, wherein the temperature of the solid surface is at −90° C. or below, in a manner that maintains the droplet as a single droplet as it contacts and freezes on the surface as a frozen pellet;
b) applying microwave radiation in a traveling wave format at a power in a range of between 0.5 and 8 KW/hr/Kg to the frozen pellet under a pressure below atmospheric pressure to produce a dried pellet;

wherein the drying yield, as obtained by a plaque assay, is greater than or equal to 50%.

2. The method of claim 1 , wherein the solid surface is a flat surface.

3. The method of claim 1 , wherein the solid surface has one or more cavities or wells for dispensing the liquid droplets.

4. The method of claim 1 , wherein the dispensing is performed from a dispensing tip at a speed and at a gap distance that prevents freezing of any portion of the aliquot and maintains the dispensed droplet in simultaneous contact with the solid surface and the open end of the dispensing tip until the surface of the dispensed droplet touching the solid surface is frozen.

5. The method of claim 4 , wherein the dispensing speed is selected from the group consisting of: about 3 ml/min to about 75 ml/min; about 5 ml/min to about 75 ml/min; about 3 ml/min to about 60 ml/min, about 20 ml/min to about 75 ml/min; and about 20 ml/min to about 60 ml/min.

6. The method of claim 4 , wherein the surface temperature of the solid surface is below −150° C. and the gap distance between the open end of the dispensing tip and the solid surface is between 0.1 cm and 0.5 cm or between 0.1 cm and 1 cm or between 0.1 cm and 0.75 cm.

7. The method of claim 1 , wherein the liquid composition comprises a total solute concentration of at least 20% on a weight by weight basis.

8. The method of claim 1 , further comprising measuring the reconstitution time of the dried pellet.

9. The method according to claim 1 , wherein the liquid composition is sublimated in less than 12 hours.

10. The method according to claim 1 , wherein the pressure is in the range of 20 to 500 mTorr.

11. The method according to claim 1 , wherein the temperature of the dried pellet in step b) does not exceed 45° C.

12. The method according to claim 1 , wherein the microwave radiation is applied in a continuous or semi-continuous mode.

13. The method according to claim 1 , wherein the liquid composition contains sugar in an amount chosen from the group that consists of the ranges 20-55% w/w, 20-50% w/w, 20-45% w/w, 25-45% w/w, 25-47.5% w/w, 25-40% w/w, 30-47.5% w/w, 30-40% w/w, 25-35% w/w or 27-30% w/w.

14. A container containing at least one dried pellet prepared by the method of claim 1 .

15. The container of claim 14 , wherein the dried pallet has a reconstruction time of less than 5 minutes or less than 2 minutes or less than 1 minute.

16. The container of claim 14 , wherein the container is selected from glass vial, resin vials, plastic vials, dual cartridge device, or foil-pouch based devices vaccine.

17. The container of claim 14 , wherein the moisture content of the liquid composition after drying is less than 60%.

Assignees

• Merck Sharp & Dohme

Inventors

• Bhambhani Akhilesh
• Evans Robert K
• Sinacola Jessica
• Lizzano Rebecca

Classifications

• C07K1/00

  General methods for the preparation of peptides {, i.e. processes for the organic chemical preparation of peptides or proteins of any length} · CPC title

• A61K9/0014

  Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00) · CPC title

• F26B2200/08

  Granular materials · CPC title

• A61K2039/525

  Virus · CPC title

• F26B5/048 Primary

  in combination with heat developed by electro-magnetic means, e.g. microwave energy · CPC title