Storage-stable transdermal patch

• US 5,008,110 A
• Filed: 11/10/1988
• Issued: 04/16/1991
• Est. Priority Date: 11/10/1988
• Status: Expired due to Term

• Current Assignee: The Procter & Gamble Company
• Original Assignee: The Procter & Gamble Company
• Inventors: Benecke, Arnold G., Wnuk, Andrew J., Kinne, Daniel J.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US07/269,513
• Time in Patent Office: 887 Days
• Field of Search: 424/449, 424/448
• US Class Current: 424/448
• CPC Class Codes: A61F 13/022 having more than one layer with different fluid retention characteristics
• CPC Class Codes: A61F 13/0259 characterised by the release liner covering the skin adhering layer
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

Abstract

A shelf-stable device for transdermally administering an active pharmaceutical to a patient. The device includes a drug reservoir that contains the drug formulation. In one preferred embodiment of the present invention, the drug reservoir is sandwiched between an upper and a lower solvent barrier film that are made from a material such as a polyester that will not absorb the drug and/or skin permeating enhancing solvent, if any, contained within the reservoir. The drug reservoir and solvent barrier films are encapsulated within a hermetically-sealed compartment that protects the drug formulation from common environmental factors such as water vapor, oxygen, and light which can adversely affect the stability and efficacy of the drug formulation. The hermetically-sealed compartment also prevents the drug formulation from coming into contact with and possibly dissolving the adhesive used to secure the device to the patients'"'"'s skin. In another particularly preferred embodiment of the present invention, the device'"'"'s drug reservoir is encapsulated within a hermetically-sealed compartment that is made from solvent/environment barrier films that serve the dual functions of preventing the device'"'"'s components from absorbing the drug/solvent formulation from the reservoir, and protecting the drug/solvent formulation from common environmental factors.

Claims

1. A storage-stable device for the transferal delivery of an active pharmaceutical, said device comprising:

(a) a drug reservoir containing a mixtured of said pharmaceutical and a skin permeation enhancer, said reservoir having an upper surface and a lower surface;

(b) a lower barrier film which is resistant to permeation by and absorption of said pharmaceutical and said skin permeation enhancer in contact with said lower surface of said reservoir;

(c) an upper barrier film which is resistant to permeation by and absorption of said pharmaceutical and said skin permeation enhance in contact with said upper surface of said reservoir;

(d) a compartment containing said drug reservoir and said lower and said upper barrier films, said compartment comprising a top cover located adjacent and secured to said upper barrier film and a bottom cover located adjacent and secured to said lower barrier film, each of said covers being comprised of a material which is resistant to permeation by moisture, oxygen and light, said top cover and aid bottom cover being hermetically sealed together smear their peripheral edges;

(e) an outermost coverstock attached to said bottom cover of said outer compartment, said coverstock having an adhesive coating thereon, said hermetically-sealed compartment and said upper and lower barrier films together preventing said mixture of said pharmaceutical and said skin permeation enhancer from coming into contact with said adhesive coating on said outermost coverstock as well as the entry of moisture, oxygen and light from the surrounding environment into said reservoir; and

(f) a release liner attached to said top cover of said compartment, said release liner being in contact with the periphery of said outermost coverstock, whereby peeling said release liner from said coverstock breaks said hermetic seal between said top cover and said bottom cover o said compartment, thereby exposing the adhesive at the periphery of said outermost coverstock and the upper surface of said drug reservoir.

2. The transdermal device recited in claim 1 further comprising:

(g) a release tab interposed between said adhesive-coated coverstock and said release liner at an outer margin of said device.

3. The transdermal device recited in claim 1 further comprising:

(h) a rate-controlling or nonrate-controlling membrane interposed between said reservoir and said upper barrier film.

4. The transdermal device recited in claim 1 wherein said upper and lower barrier films are made from a laminate comprised of an outer heat-sealable layer and an inner reservoir-contacting layer.

5. The transdermal device recited in claim 4 wherein said inner reservoir-contacting layer is made from a material selected from the group consisting of polyethylene terephthalate, fluorinated polyethylene terephthalate, a rubber modified acrylonitrile copolymer, nylon, EVOH, styrene acrylonitrile copolymer, polyvinylidine chloride copolymer, and polychlorotrifluoroethylene copolymer.

6. The transdermal device recited in claim 1 wherein said top cover and said bottom cover of said hermetically-sealed compartment are made from a laminate comprised of an outer heat-sealable layer, at least one intermediate environment barrier layer which is resistant to permeation by moisture, oxygen and light from the surrounding environment, and an inner heat-sealable layer.

7. The transdermal device recited in claim 6 wherein said environment barrier layer is selected from the group consisting of polyethylene terephthalate, metallized polyethylene terephthalate, metal foils, a polyvinylidine chloride copolymer, a rubber modified acrylonitrile copolymer, nylon, EVOH, and polychlorotrifluoroethylene copolymer.

9. The transdermal device recited in claim 1 wherein said skin permeation enhancer is selected from the group consisting of polar solvent materials, polar lipid materials, and mixtures thereof.

10. The transdermal device recited in claim 9 wherein said polar solvent materials are selected from the group consisting of C₃ -C₄ diols, C₃ -C₆ triols, and mixtures thereof;

and wherein said polar lipid materials are selected from the group consisting of fatty alcohols, fatty acids, fatty alcohol esters, fatty acid esters, and mixtures thereof.

11. The transdermal device recited in claim 9 wherein said polar solvent material is propylene glycol, and wherein said polar lipid material is methyl laurate or methyl caprylate.

12. The transdermal device of claim 9, claim 10 or claim 11, wherein said pharmaceutical is comprised of buprenorphine.

8. A storage-stable device for the transdermal delivery of an active pharmaceutical, said device comprising:

(a) a drug reservoir containing a mixture of said pharmaceutical and a skin permeation enhancer, said reservoir having an upper surface and a lower surface;

(b) a lower barrier film, which is resistant to permeation by and absorption of said pharmaceutical and said skin permeation enhancer as well as resistant to permeation by moisture, oxygen and light, in contact with said lower surface of said reservoir;

(c) an upper barrier film, which is resistant to permeation by and absorption of said pharmaceutical an said skin permeation enhancer as well as resistant to permeation by moisture, oxygen and light, in contact with said upper surface of said reservoir, said lower and said upper barrier films being hermetically sealed together near their peripheral edges;

(d) an outermost coverstock attached to said lower barrier film, said coverstock having an adhesive coating thereon, said hermetically sealed lower and upper barrier films preventing said mixture of said pharmaceutical and said skin permeation enhancer from coming into contact with said adhesive coating on said outermost coverstock as well as the entry of moisture, oxygen and light from the surrounding environment into said reservoir; and

(e) a release liner attached to said upper barrier film, said release liner being in contact with the periphery of said outermost coverstock, whereby peeling said release liner from said coverstock breaks said hermetic seal between said lower and said upper barrier films, thereby exposing the adhesive at the periphery of said outermost coverstock and the upper surface of said drug reservoir.

13. The transdermal device recited in claim 8 further comprising:

(f) a release tab interposed between said adhesive-coated coverstock and said release liner at an outer margin of said device.

14. The transdermal device recited in claim 8 further comprising:

(g) a rate-controlling or nonrate-controlling membrane interposed between said reservoir and said upper barrier film.

15. The transdermal device recited in claim 8 wherein said upper and said lower barrier films are made from a laminate comprised of an outer layer and an inner heat-sealable layer.

16. The transdermal device recited in claim 8 wherein said outer layer is made from a material selected from the group consisting of polyethylene terephthalate, metallized polyethylene terephthalate, polyvinylidine chloride copolymer, polychlorotrifluoroethylene copolymer, metal foil, polyolefins, metallized polyolefins, EVOH, nylon, rubber modified acrylonitrile copolymers, and multilaminate combinations thereof, and wherein said inner heat-sealable layer is a PET-G or modified PET-G.

17. The transdermal device of claim 18, claim 19 or claim 20, wherein said pharmaceutical is comprised of buprenorphine.

18. The transdermal device recited in claim 8 wherein said skin permeation enhancer is elected from the group consisting of polar solvent materials, polar lipid materials, and mixtures thereof.

19. The transdermal device recited in claim 8 wherein said polar solvent materials are selected from the group consisting of C₃ -C₄ diols, C₃ -C₆ triols, and mixtures thereof;

and wherein said polar lipid materials are selected from the group consisting of fatty alcohols, fatty acids, fatty alcohol users, fatty acid esters, and mixtures thereof.

20. The transdermal device recited in claim 8 wherein said polar solvent material is propylene glycol, and wherein said polar lipid material is methyl laurate or methyl caprylate.