Titratable dosage transdermal delivery system

• US 6,682,757 B1
• Filed: 11/16/2000
• Issued: 01/27/2004
• Est. Priority Date: 11/16/2000
• Status: Expired due to Term

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Euroceltique SA
• Inventors: Wright, Curtis
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Ware, Todd D
• Application Number:
  US09/714,604
• Time in Patent Office: 1,167 Days
• Field of Search: 424/448, 424/449, 424/435, 424/434, 602/58
• US Class Current: 424/448
• CPC Class Codes: A61F 2013/0296 for making transdermal patches (chemical processes excluded)
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• 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 9/7038 Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
• 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: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to a titratable dosage transdermal delivery system for systemic delivery of a therapeutic agent or drug. The system comprises a plurality of patch units that are connected along one or more borders. The plurality of patch units are divisible into units along the one or more borders having one or more lines of separation. Each patch unit is surrounded by a border. The therapeutic patch has at least a backing layer and a therapeutic agent comprising layer. The dosage of therapeutic agent delivered to a patient is proportional to the number of patch unit applied per treatment. The system enables systemic administration of a titratable dosage of therapeutic agent, adjustable by the patient under the direction of a physician, through the skin or mucosa. Moreover, the invention relates to a method of making the titratable dosage transdermal delivery system. Furthermore, the invention relates to a method of providing a titratable amount of therapeutic agent to a patient using the transdermal delivery system of the invention.

Claims

1. A method of delivering a hormone through a patient'"'"'s skin comprising:

(a) providing a transdermal delivery system that comprises a plurality of patch units, wherein each patch unit comprises a backing layer having one or more borders, a drug layer comprising a hormone disposed on the backing layer, and an adhesive layer, wherein at least a portion of the adhesive layer is disposed on the borders of the backing layer;

the plurality of patch units are connected to each other along one or more borders of the patch units; and

each patch unit is defined by one or more lines of separation along the borders of the patch units;

(b) separating at least one patch unit from the transdermal delivery system along at least one line of separation; and

(c) applying at least one patch unit such that the drug layer makes contact with the skin.

2. The method of claim 1 wherein the patch units are applied on the skin of the planter foot arch, lateral ankle, palm, upper arm, ventral forearm, dorsal forearm, back, chest, thigh, abdomen, scalp, axilla, forehead, lower back, chest, buttocks or scrotum.

3. The method of claim 1 wherein a portion of the adhesive layar is disposed on the drug layer;

and a cover layer is disposed on the adhesive layer.

4. The method of claim 1 wherein the hormone is selected from the group consisting of adrenocorticosteroids, 6-α

-methylprednisolone, androgenic steroids, methyltestosterone, fluoxymesterone, progesterone, norethindrone, thyroxine, and insulin.

5. The method of claim 3 wherein said transdermal delivery system further comprises a release limiting layer disposed on the drug layer.

6. The method of claim 1 wherein the hormone is encapsulated by microcapsules.

7. The method of claim 1 wherein the drug layer comprises about 0.1-90% by weight of a hormone.

8. The method of claim 1 wherein the drug layer comprises about 10-45% by weight of a hormone.

9. The method of claim 1 wherein the drug layer comprises about 25-40% by weight of a hormone.

10. The method of claim 1 wherein the drug layer further comprises a softening agent selected from the group consisting of dodecanol, undecanol, octoanol, and esters of carboxylic acids.

11. The method of claim 1 wherein the drug layer further comprises a permeation enhancing agent.

12. The method of claim 3 wherein the cover layer comprises a notch so as to facilitate separation of the cover layer from the adhesive layer.

13. The method of claim 1 wherein the transdermal delivery system is stored in a resealable pouch.

14. The method of claim 1 wherein the lines of separation are parallel and/or perpendicular to each other.

15. The method of claim 1 wherein the lines of separation are lines of perforations.

16. The method of claim 1 wherein the lines of separation are spaced at regular intervals.

17. The method of claim 1 wherein the lines of separation are about 1 cm to 6 cm apart.

18. The method of claim 1 wherein 2 to 5 patch units are connected in series in the transdermal delivery system.

19. The method of claim 1 wherein 4 patch units are arranged in 2 rows and 2 columns in the transdermal delivery system.

20. The method of claim 1 wherein the drug layer is a reservoir layer.

21. The method of claim 1 wherein the drug layer is a drug-in-matrix layer.

22. The method of claim 1 wherein the drug layer is a drug-in-adhesive layer.

23. The method of claim 1 wherein two to five patch units are applied on the skin.

24. A method of adjusting the therapeutic dosage of hormone delivery through a patient'"'"'s skin, the method comprising:

(a) providing a transdermal delivery system that comprises a plurality of patch units, wherein each patch unit comprises a backing layer having one or more borders, a drug layer comprising a hormone disposed on the backing layer, and an adhesive layer, wherein at least a portion of the adhesive layer is disposed on the borders of the backing layer;

the patch units are connected to each other along one or more borders of the patch units; and

each patch unit is defined by one or more lines of separation along the borders of the patch units;

(b) separating a first number of patch units from the transdermal delivery system along at least one line of separation;

(c) applying the first number of patch units such that the drug layer makes contact with the skin;

(d) thereafter, separating a second number of patch units from the delivery system along at least one line of separation, the second number of patch units being different than or the same as the first number of patch units; and

(e) applying the second number of patch units such that the drug layer makes contact with the skin.

25. The method of claim 24 wherein one or more patch units from the first number of patch units are removed from the skin before applying the second number of patch units to the skin.

26. The method of claim 24 wherein one or more patch units from the first number of patch units remain on the skin before applying the second number of patch units to the skin.

27. The method of claim 24 wherein the hormone is selected from the group consisting of adrenocorticosteroids, 6-α

-methylprednisolone, androgenic steroids, methyltestosterone, fluoxyrnesterone, progesterone, norethindrone, thyroxine, and insulin.

28. The method of claim 24 comprising increasing the dosage of hormone through the patient'"'"'s skin, wherein the second number of patch units is greater than the first number of patch units.

29. The method of claim 24 comprising decreasing the dosage of hormone through the patient'"'"'s skin, wherein the second number of patch units is less than the first number of patch units.