Transdermal drug delivery system

• US 5,667,798 A
• Filed: 06/07/1995
• Issued: 09/16/1997
• Est. Priority Date: 12/30/1993
• Status: Expired due to Fees

• Current Assignee: Harrogate Holdings New Jersey Inc.
• Original Assignee: Harrogate Holdings Limited
• Inventors: Royds, Robert B., Lim, John, Rosen, Joel D.
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/477,914
• Time in Patent Office: 832 Days
• Field of Search: 424/447, 424/448, 424/449
• US Class Current: 424/449
• 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
• CPC Class Codes: A61K 9/7092 Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
• CPC Class Codes: A61M 35/006 using sponges, foams, absorbent pads or swabs as spreading means
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

In a transdermal drug delivery system, encapsulation material used to coat drug granules controls the release of an active ingredient. The active ingredient is released into a water retaining matrix, which acts as a reservoir, and transdermal drug penetration is driven by the resulting concentration gradient. The delivery system is enclosed in a patch comprising a composite shell, which acts as an occlusive covering when attached to skin, thus enhancing the hydration of the skin area and fostering absorption of the drug. Visible change indicators incorporated into the system provide indicators at significant "landmarks" in the lifetime of the patch. Microcapsules used for the indicator may be formulated so that the penetration of moisture effects a color change at a time when the active ingredient is almost exhausted. This feature alerts to the user to the need for application of a replacement patch.

Claims

1. A drug delivery system for the release and delivery of a drug across the skin of a user comprising:

a shell, said shell providing an occlusive covering on the skin of the user to enhance the hydration of the skin, said shell comprising a reservoir having a first face and a second face, said reservoir having therein a matrix adapted to absorb moisture from the skin and hydrate the skin to facilitate penetration of the skin by a drug, said reservoir further having therein a plurality of microcapsules, said microcapsules being dispersed within said matrix and having contained therein an effective concentration of a drug and a coating formulated to be susceptible to penetration by moisture;

means on said first face of said reservoir for adhering said shell to the skin; and

a visible indicator operatively associated with said second face of said reservoir, said indicator comprising a reagent formulated to visibly change in response to the presence of moisture, electrolytes or other secretions in said matrix, wherein said release of said drug and said visible indicator are activated by a common mechanism.

2. A delivery system in accordance with claim 1, wherein said indicator is a color indicator, said indicator comprising a plurality of microparticles permeable to moisture and having contained therein a chemical intermediate adapted to absorb moisture from said matrix and to irreversibly change color in response to the moisture level in said matrix.

3. A delivery system in accordance with claim 2, wherein said microcapsules are uniformly dispersed within said matrix.

4. A delivery system in accordance with claim 2 wherein said drug containing-microcapsules are so constructed as to control the rate of release of said drug into said matrix.

5. A delivery system in accordance with claim 4, wherein said chemical intermediate containing-microcapsules are so constructed as to control the rate of absorption of said moisture.

6. A delivery system in accordance with claim 5, wherein said color change is indicative of the release of said drug from said microcapsules and the depletion of said drug from said microcapsules.

7. A delivery system in accordance with claim 6, wherein said color change is indicative of the lifetime of said system.

8. A delivery system in accordance with claim 7, wherein said matrix is adapted to absorb moisture from the skin several times the weight of said matrix.

9. A delivery system in accordance with claim 8, wherein said matrix is selected from the group consisting of guar, acacia, xantham gums.

10. A delivery system in accordance with claim 8, wherein said matrix is selected from the group consisting of a gelling agent selected from the group consisting of carboxypolymethylene, hydroxyethylcellulose and polyacrylamide.

11. A delivery system in accordance with claim 8, wherein said drug is for the chemoprophylaxis of malaria.

12. A delivery system in accordance with claim 8, wherein said drug comprises an analgesic for use in peri-operative and post-operative pain relief.

13. A delivery system in accordance with claim 8, wherein said system is adapted for the topical delivery of anesthetic agents.

14. A delivery system in accordance with claim 8, wherein said drug comprises an antibiotic agent.

15. A delivery system in accordance with claim 8, wherein said drug comprises medication for treating the central nervous system.

16. A drug delivery system for the release and delivery of a drug across the skin of a user comprising:

a shell, said shell providing an occlusive covering on the skin of the user to enhance the hydration of the skin, said shell comprising a reservoir having a first face and a second face, said reservoir having therein a matrix adapted to absorb moisture from the skin and hydrate the skin, said reservoir further having therein a plurality of microcapsules, said microcapsules being dispersed within said matrix and having contained therein an effective concentration of a drug, said microcapsules being permeable to moisture and adapted to release said drug in response to the presence of moisture in said matrix; and

a visible indicator operatively associated with said reservoir, said indicator comprising a plurality of microparticles dispersed within said matrix and having a reagent formulated to change color in response to the presence of moisture in said matrix, wherein said release of said drug and said visible indicator are activated by a common mechanism.