Method of transdermal drug delivery

• US 4,834,978 A
• Filed: 02/08/1988
• Issued: 05/30/1989
• Est. Priority Date: 10/01/1984
• Status: Expired due to Term

• Current Assignee: BioTex Incorporated
• Original Assignee: BioTex Incorporated
• Inventors: Nuwayser, Elie S.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US07/153,147
• Time in Patent Office: 477 Days
• Field of Search: 424/449, 424/448
• US Class Current: 424/448
• 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 transdermal drug delivery system useful for the controlled, for example, zero order, release of one or more drugs to a selected skin area of a user, which system comprises a reservoir containing a transdermal delivery composition. The reservoir contains a composition which comprises a base material, which is a solid but which melts or liquefies upon contact with the skin of a user and selected to occlude the skin of the user to force hydration of the stratum corneum with water from the lower layers of the epidermis of the user and a plurality of solid microparticles, generally uniformly dispersed and suspended in the base material, the microparticles containing an effective, therapeutic amount of the drug for transdermal delivery, such as the contraceptive steroid. In use, the base material forms a thermodynamically stable thin film layer in intimate contact with the skin while the drug is released from the microparticles into the base material and transdermally into the user through the thin liquid film of the base material.

Claims

1. A transdermal drug delivery system, which system comprises:

(a) an impervious backing sheet;

(b) the reservoir containing a transdermal drug delivery composition, which comprises;

(i) a dermatologically-acceptable, semi-solid or solid base material, which base material is selected on application to the skin of the user to melt or liquefy and form a thin, liquid film and to occlude the skin of the user and to force hydration of the stratum corneum layer with water from the lower layers of the epidermis of the user in use;

(ii) a plurality of solid polymeric microparticles generally uniformly dispersed and suspended in the base material in the reservoir, the microparticles having a particle size of less than about 1000 microns and containing an effective, therapeutic amount of a drug for transdermal delivery in a controlled release pattern, the active drug material for transdermal delivery and the base material being compatible to form a compatible transport relationship; and

whereby, on application to the skin of a user the base material melts or liquefies to form a thin, liquid film on the skin of the user, while the drug is released at a controlled release rate from the suspended microparticles into the solid or semi-solid base material and through the liquid film directly into the skin of the user.

2. The drug delivery system of claim 1 wherein the base material melts and forms a liquid at about 34°

C. to 37°

C.

3. The drug delivery system of claim 1 wherein the base material comprises a hydrophilic material and the drug to be delivered comprises a water soluble drug.

4. The drug delivery system of claim 1 wherein the base material comprises a hydrophobic material and the drug to be transdermally delivered comprises a hydrophobic drug.

5. The drug delivery system of claim 1 wherein the base material comprises a glycerol, water-containing, liquid-base material and wherein the drug to be transdermally delivered comprises a water soluble drug.

6. The drug delivery system of claim 1 wherein the base material comprises a hydrocarbon material and wherein the drug to be transdermally delivered comprises a hydrophobic drug soluble in the hydrocarbon base material.

7. The drug delivery system of claim 1 wherein the active drug comprises a steroid hormone.

8. The drug delivery system of claim 7 wherein the steroid hormone comprises norethindrone, norgestrel, estradiol, levonorgestrel and mestranol and combinations thereof.

9. The drug delivery system of claim 1 wherein the base material comprises a mixture of a polyalkylene glycol and water.

10. The drug delivery system of claim 1 wherein the base material comprises a mixture of polyethylene glycol and up to 20% by weight water.

11. The drug delivery system of claim 1 which includes a means to seal the face of the reservoir prior to use;

and means to secure the membrane face to the skin of the user.

12. The drug delivery system of claim 1 wherein the microparticle comprises a microparticle having a particle size of about 200 microns or less and wherein the active ingredient comprises a levonorgestrel or estradiol wherein the active drug is admixed with a lactide or glycolide polymer and wherein the microparticle has a wall composed of a lactide or glycolide polymer.

13. The drug delivery system of claim 1 wherein the microparticles comprise a solid admixture of the drug and a biodegradable polymer and a thin outer layer of a biodegradable polymer.

14. A composition for the accelerated transdermal controlled delivery of a drug to a user, which composition comprises:

(a) a meltable semi-solid or solid base material, which, on application to the skin of the user, melts to form a thin liquid film and selected to occlude the skin of the user and to force hydration of the stratum corneum layer with water from the lower layers of the epidermis of the user in use; and

(b) a plurality of solid polymeric microparticles generally uniformly dispersed and suspended in the base material, the microparticles having a particle size of less than about 1000 microns and containing an effective, therapeutic amount of a drug for transdermal delivery, the active drug material for transdermal delivery and the base material being compatible to form a compatible transport relationship;

whereby, on application to the skin of a user of the transdermal drug composition the drug is released at a controlled rate from the suspended microparticles into the base material and into the skin of the user.

15. The composition of claim 14 wherein the base material melts and forms a liquid of about 34°

C. to 37°

C.

16. The composition of claim 14 wherein the base material comprises a glycerol, water-containing, liquid base material and wherein the drug to transdermally delivered comprises a water soluble drug.

17. The composition of claim 14 wherein the base material comprises a hydrocarbon material and wherein the drug to be transdermally delivered comprises a hydrophobic drug soluble in the hydrocarbon base material.

18. The composition of claim 14 wherein the active drug comprises a steroid hormone.

19. The composition of claim 18 wherein the steroid hormone comprises norethindrone, norgestrel, estradiol, levonorgestrel and mestranol and combinations thereof.

20. The composition of claim 14 wherein the base material comprises a mixture of a polyalkylene glycol and water.

21. The composition of claim 14 wherein the base material comprises a mixture of polyethylene glycol and up to 20% by weight water.

22. The composition of claim 14 wherein the microparticle comprises a microparticle having a particle size of about 200 microns or less, wherein the active ingredient comprises a levonorgestel or estradiol wherein the active drug is admixed with a lactide or glycolide polymer and wherein the microparticle has a wall composed of a lactide or glycolide polymer.

23. The composition of claim 14 wherein the microparticles comprise a solid admixture of the drug and a biodegradable polymer and a thin outer layer of a biodegradable polymer.