Method for terminal sterilization of transdermal delivery devices

• US 20060275170A1
• Filed: 06/01/2006
• Published: 12/07/2006
• Est. Priority Date: 06/02/2005
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Maa, Yuh-Fun, Ameri, Mahmoud
• Application Number:
  US11/446,487
• Publication Number:
  US 20060275170A1
• Time in Patent Office: Days
• US Class Current: 422/22
• CPC Class Codes: A61K 41/17 by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61L 2/081 Gamma radiation
• CPC Class Codes: A61L 2/087 Particle radiation, e.g. electron-beam, alpha or beta radiation
• CPC Class Codes: A61L 2/206 Ethylene oxide
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using 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

Abstract

An method and system for providing a terminally sterilized transdermal device adapted to delivery a PTH-based agent. A microprojection member that includes a plurality of stratum comeum-piercing microprojections is coated with PTH-based agent formulation an exposed to sufficient radiation to sterilize the microprojection member while retaining sufficient activity of the PTH-based agent. Preferably, the microprojection member is sealed in packing with an inert atmosphere and reduced moisture. The sterilizing radiation can be gamma radiation or e-beam, preferably delivered in a dose in the range of approximately 5-50 kGy. Also preferably, the irradiation is performed at −78.5-25° C. In preferred embodiments, the radiation is delivered at a rate greater than 3.0 kGy/hr.

Claims

1. A method for terminally sterilizing a transdermal device adapted to deliver a PTH-based agent, comprising the steps of:

providing a microprojection member having a plurality of microprojections that are adapted to pierce the stratum comeum of a patient having a biocompatible coating disposed on said microprojection member, said coating being formed from a coating formulation having at least one PTH-based agent disposed thereon; and

exposing said microprojection member to radiation selected from the group consisting of gamma radiation and e-beam, wherein said radiation is sufficient to reach a desired sterility assurance level.

2. The method of claim 1, further comprising the step of sealing said microprojection member inside packaging adapted to control environmental conditions surrounding said microprojection member.

3. The method of claim 2, wherein said packaging comprises a foil pouch.

4. The method of claim 2, further comprising the step of sealing a desiccant inside said packaging.

5. The method of claim 2, further comprising the step of mounting said microprojection member on a pre-dried retainer ring prior to sealing said microprojection member inside said packaging.

6. The method of claim 4, further comprising the step of mounting said microprojection member on a pre-dried retainer ring prior to sealing said microprojection member inside said packaging.

7. The method of claim 2, further comprising the step of purging said packaging with an inert gas prior to sealing said microprojection member.

8. The method of claim 7, wherein said inert gas comprises nitrogen.

9. The method of claim 2, wherein said step of exposing said microprojection member to radiation occurs at approximately −

78.5-25°

C.

10. The method of claim 2, wherein said step of exposing said microprojection member to radiation occurs at an ambient temperature.

11. The method of claim 2, wherein said step of exposing said microprojection member to radiation comprises delivering in the range of approximately 5 to 50 kGy.

12. The method of claim 2, wherein said step of exposing said microprojection member to radiation comprises delivering approximately 7 kGy.

13. The method of claim 2, wherein said step of exposing said microprojection member to radiation comprises delivering approximately 21 kGy.

14. The method of claim 2, wherein said step of exposing said microprojection member to radiation comprises delivering radiation at a rate of greater than approximately 3.0 kGy/hr.

15. The method of claim 2, wherein said sterility assurance level is 10⁻

6.

16. The method of claim 2, further comprising the step of adding an antioxidant to said coating formulation.

17. A method for terminally sterilizing a transdermal device adapted to deliver a PTH-based agent, comprising the steps of:

providing a microprojection member having a plurality of microprojections that are adapted to pierce the stratum comeum of a patient having a biocompatible coating disposed on said microprojection member, said coating being formed from a coating formulation having at least one PTH-based agent disposed thereon;

sealing said microprojection member with a desiccant inside packaging purged with nitrogen and adapted to control environmental conditions surrounding said microprojection member; and

exposing said microprojection member to radiation selected from the group consisting of gamma radiation and e-beam radiation, wherein said radiation is sufficient to reach a desired sterility assurance level.

18. The method of claim 17, further comprising the step of mounting said microprojection member on a pre-dried retainer ring prior to sealing said microprojection member inside said packaging.

19. The method of claim 17, wherein said step of exposing said microprojection member to radiation comprises delivering a dose of radiation in the range of approximately 7-21 kGy.

20. The method of claim 19, wherein said step of exposing said microprojection member to radiation occurs at a temperature up to approximately 25°

C.

21. The method of claim 17, wherein said PTH-based agent retains at least approximately 96% of initial purity.

22. The method of claim 21, wherein said PTH-based agent retains at least approximately 98% of initial purity.

23. A method for terminally sterilizing a transdermal device adapted to deliver a PTH-based agent, comprising the steps of:

providing a microprojection member having a plurality of microprojections that are adapted to pierce the stratum corneum of a patient having a biocompatible coating disposed on said microprojection member, said coating being formed from a coating formulation having at least one PTH-based agent disposed thereon;

sealing said microprojection member inside packaging purged with an inert gas and adapted to control environmental conditions surrounding said microprojection member; and

exposing said microprojection member to e-beam radiation, wherein said radiation is sufficient to reach a desired sterility assurance level.

24. A method for terminally sterilizing a transdermal device adapted to deliver a PTH-based agent, comprising the steps of:

providing a microprojection member having a plurality of microprojections that are adapted to pierce the stratum comeum of a patient having a biocompatible coating disposed on said microprojection member, said coating being formed from a coating formulation having at least one PTH-based agent disposed thereon;

placing said microprojection member inside packaging adapted to control environmental conditions;

reducing moisture content inside said packaging;

sealing said microprojection member with said packaging; and

exposing said microprojection member to radiation selected from the group consisting of gamma radiation and e-beam, wherein said radiation is sufficient to reach a desired sterility assurance level.

25. A transdermal system, adapted to deliver a PTH-based agent, comprising:

a microprojection member including a plurality of microprojections that are adapted to pierce the stratum comeum of a patient having a biocompatible coating disposed on said microprojection member, said coating being formed from a coating formulation having at least one PTH-based agent disposed thereon; and

packaging purged with an inert gas and adapted to control environmental conditions sealed around said microprojection member;

wherein said sealed package has been exposed to radiation to sterilize the microprojection member.

26. The system of claim 25, further comprising a desiccant sealed inside said packaging with said microprojection member.

27. The system of claim 25, wherein said microprojection member is mounted on a pre-dried retainer ring.

28. The system of claim 25, wherein said packaging is purged with nitrogen.

29. The system of claim 25, wherein said packaging comprises a foil pouch.

30. The system of claim 25, wherein said PTH-based agent comprises hPTH (1-34).

31. A transdermal system, adapted to deliver a PTH-based agent, comprising:

a microprojection member including a plurality of microprojections that are adapted to pierce the stratum comeum of a patient;

a hydrogel formulation having at least one PTH-based agent, wherein said hydrogel formulation is in communication with said microprojection member; and

packaging purged with an inert gas and adapted to control environmental conditions sealed around said microprojection member;

wherein said sealed package has been exposed to radiation to sterilize the microprojection member.

32. A transdermal system, adapted to deliver a PTH-based agent, comprising:

a microprojection member including a plurality of microprojections that are adapted to pierce the stratum comeum of a patient;

a solid film disposed proximate said microprojection member, wherein said solid film is made by casting a liquid formulation comprising at least one PTH-based agent, a polymeric material, a plasticizing agent, a surfactant and a volatile solvent; and

packaging purged with an inert gas and adapted to control environmental conditions sealed around said microprojection member;

wherein said sealed package has been exposed to radiation to sterilize the microprojection member.