Stabilization of alum-adjuvanted immunologically active agents

• US 20060067943A1
• Filed: 09/27/2005
• Published: 03/30/2006
• Est. Priority Date: 09/28/2004
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Sellers, Scott, Maa, Yuh-Fun
• Application Number:
  US11/237,200
• Publication Number:
  US 20060067943A1
• Time in Patent Office: Days
• US Class Current: 424/184.100
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2730/10134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

A composition and method for formulating and delivering an adjuvanted immunological active agent, especially a vaccine, wherein adjuvant coagulation and concomitant loss of vaccine efficacy enhancement is mitigated or avoided. The adjuvanted, immunologically-active agent can be subjected to freezing, drying, freeze-drying, or lyophilization, and when reconstituted, retains a high level of potency. The present invention further provides for a composition and method for formulating and delivering a stable, adjuvanted, immunologically-active agent capable of being deposited on a transdermal delivery device or microprojection or array thereof.

Claims

1. An immunologically active agent-containing formulation, the formulation comprising:

a biologically effective amount of an immunologically active agent;

a stabilizing amount of a carbohydrate sugar; and

an amount of an aluminum salt to minimize the loss of immunogenicity of the immunologically active agent when being subjected to drying.

2. The formulation of claim 1, wherein coagulation of the aluminum salt is minimized to preserve the potency and immunogenicity of the formulation.

3. The formulation of claim 1, wherein the aluminum salt is aluminum hydroxide, aluminum phosphate, or mixtures thereof.

4. The formulation of claim 1, wherein the formulation contains about 0.0001% to 3% weight percent of the aluminum salt based on the total weight of the formulation.

5. The formulation of claim 1, wherein the sugar is selected from the group consisting of sucrose, metezitose, raffinose, trehalose, stachyose, lactose, maltose and combinations thereof.

6. The formulation of claim 1, wherein the formulation contains in the range of about 2 to 40 weight percent of the sugar based on the total weight of the formulation.

7. The formulation of claim 1, further comprising a viscosity-enhancing agent.

8. The formulation of claim 7, wherein the viscosity-enhancing agent is present such that the formulation has a viscosity in the range of about 1 to 50 centipoises.

9. The formulation of claim 1, further comprising a film-forming agent.

10. The formulation of claim 9, wherein the film-forming agent is present in the formulation in the range of about 0.001 to 10 weight percent based on the total weight of the formulation.

11. The formulation of claim 1, wherein the formulation further comprises at least one additional adjuvant.

12. The formulation of claim 1, wherein the immunologically active agent is selected from the group consisting of:

virus, bacteria, protein-based vaccine, polysaccharide-based vaccine, nucleic acid-based vaccine and combinations thereof.

13. A device for transdermally delivering an immunologically active agent, the device comprising:

a member having a plurality of stratum corneum-piercing microprojections adapted to transdermally deliver a immunologically active agent; and

a formulation of claim 1 coated on at least one of the microprojections.

14. The device of claim 13, wherein the member has a plurality of stratum corneum-piercing microprojections.

15. The device of claim 13, wherein said member is manufactured from a metal consisting of the group of stainless steel, titanium, nickel titanium alloys, or similar biocompatible materials.

16. A method of preparing an alum-adjuvanted immunologically active agent coating, the method comprising the steps of:

preparing a coating composition comprising one or more aluminum salts in a suitable solvent, wherein the total aluminum salt concentration is less than about 3 weight percent based on the total weight of the coating composition, at least one carbohydrate sugar, an optional viscosity-enhancing agent, and an immunologically active agent;

applying said coating composition to a substrate; and

drying, or allowing to dry, said applied coating composition to prepare said dried coating.

17. The method of claim 16, wherein the method comprises the further step of adding a film-forming agent to the coating composition.

18. The method of claim 16, the method further comprising the step of subjecting the coating composition to a drying process selected from the group consisting of:

spray-drying, air-drying, spray-freeze drying, freeze-drying, lyophillization or combinations thereof.

19. The method of claim 18, the method further comprising the step of reconstituting the coating composition with a solvent.

20. The method of claim 19, the method further comprising the step of applying the reconstituted coating composition to at least one stratum-corneum piercing microprojection to form a biocompatible coating.

21. The method of claim 20, wherein the biocompatible coating is applied to the at least one stratum-corneum piercing microprojections by a method selected from the group consisting of dip-coating, microfluidic spray, printing and spraying.

22. The method of claim 21, wherein the biocompatible coating is dried or allowed to dry.

23. The method of claim 21, wherein the coating composition is applied to the at least one stratum-corneum piercing microprojections in a series of applications.

24. The method of claim 23, wherein a drying step is performed between substantially all of the applications.

25. The method of claim 22, wherein the drying step is performed at an ambient temperature.

26. The method of claim 25, wherein the drying time is in the range of about 0.5 to 360 minutes.

27. The method of claim 26, wherein the drying step is performed under conditions of about 0 to 30 percent relative humidity and below ambient pressure.

28. The method of claim 20, wherein the biocompatible coating has a thickness in the range of about 0.5 to 5 microns.

29. The method of claim 23, wherein the aggregate coating thickness is in the range of about 0.5 to 5 microns.

30. A method of transdermally delivering an immunologically active agent, the method comprising:

preparing the alum-adjuvanted immunologically active agent coating of claim 20;

and

applying the member so that the immunologically active agent is delivered through the skin of a subject.