Transdermal drug delivery device

• US 4,867,982 A
• Filed: 01/26/1988
• Issued: 09/19/1989
• Est. Priority Date: 01/13/1986
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Eckenhoff, James B., Place, Virgil A., Campbell, Patricia S.
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US07/148,417
• Time in Patent Office: 602 Days
• Field of Search: 424/449, 424/DIG. 14, 424/447, 604/897
• US Class Current: 424/449
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/0041 Mammary glands, e.g. breasts, udder; Intramammary administration
• CPC Class Codes: A61K 9/7053 obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: Y10S 424/14 Topical contraceptives and spermacides

Abstract

A medical device for the transdermal delivery of an active agent through sensitive intact skin is provided. The device comprises a matrix containing the drug having reinforcing means, preferably in the form of a fabric, embedded in the upper surface of the matrix. The matrix is formed of an agent permeable material which is tacky but does not adhesively bond to the skin. The device is sufficiently flexible and deformable that the combination of tackiness, flexibility, and deformation permits the device to be maintained in agent transmitting relationship upon skin at such sensitive areas as the scrotum, labia, breast, or penis, for example. In certain embodiments, the skin distal surface is provided with a layer of an agent impermeable material to reduce transfer of the agent from the patient to others.

Claims

1. A flexible and compliant medical device for the transdermal administration of testosterone through intact skin at sensitive body locations, said device being from 2-10 mils thick and having an extension modulus at 15% elongation in at least one direction in the range of 1000 to 15,000 gm/cm², a stress decay from 15% elongation at 5 minutes in the range of 25-45%, a 2 cm wide strip of said device requiring an elongation force of from 30-300 gm to produce said 15% elongation, said device comprising, in combination;

(a) a testosterone reservoir comprisign testosterone dissolved in ethylene/vinyl acetate copolymer having a vinyl acetate content in the range of 40-60%, said reservoir having a body contacting surface through which agent is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 100-300 g/cm² at 35°

C.;

(b) fibrous reinforcing means imbedded in said reservoir to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said reservoir, said imbedded fibrous reinforcing means forming the body distal surface of said device;

said fibrous reinforcing means being non-elastically deformable in at least one direction;

whereby the body distal surface of said device retains a fibrous texture and said device is capable of non-adhesively clinging to the skin at sensitive body locations in testosterone transmitting relationship thereto.

2. The device of claim 1 wherein said reservoir comprises an ethylene/vinyl acetate copolymer having a vinyl acetate content of about 51%.

3. The device of claim 2 wherein said reinforcing means comprises a spun bonded fabric having a weight of up to about 0.3 oz./sq. yd.

4. The device of claim 1 wherein said reservoir contains up to about 2.5% testosterone.

5. The device of claim 2 wherein said reservoir contains up to about 2.5% testosterone.

6. The device of claim 1 wherein said device is free of undissolved testosterone and contains testosterone at a loading of from about 5-15 mg.

7. The device of claim 3 wherein said device is free of undissolved testosterone and contains testosterone at a loading of from about 5-15 mg.

8. The device of claim 1 wherein said reservoir comprises an ethylene/vinyl acetate copolymer having a vinyl acetate content of about 40%.

9. The device of claim 8 wherein said reinforcing means comprises a spun bonded fabric having a weight of up to about 0.3 oz./sq. yd.

10. The device of claim 8 wherein said reservoir contains up to about 2.5% testosterone.

11. The device of claim 9 wherein said reservoir contains up to about 2.5% testosterone.

12. The device of claim 9 wherein said device is free of undissolved testosterone and contains testosterone at a loading of from about 5-15 mg.

13. A method for testosterone replacement in hypogonadal males which comprises applying a device according to claim 1 to the genitalia of a hypogonadal male and maintaining said device in testosterone transmitting relationship thereto for at least about 8 hours.

14. The method of claim 13 wherein said device is replaced with a fresh device on a daily basis for so long as testosterone replacement is desired.

15. A method for testosterone replacement in hypogonadic males which comprises applying the device of claim 1 to the scrotum of a hypogonadic male and maintaining said system in testosterone transferring relationship to said scrotum for a least about 8 hours.

16. The method of claim 15 wherein said system is maintained in place for up to about 24 hours and is replaced with a fresh device on a daily basis for so long as testosterone replacement is desired.

17. A method for testosterone replacement in hypogonadal males which comprises applying a device according to claim 1 to the genitalia of a hypogonadal male and maintaining said device in testosterone transmitting relationship thereto for a least about 8 hours.

18. The method of claim 17 wherein said device is replaced with a fresh device on a daily basis for so long as testosterone replacement is desired.

19. A method for testosterone replacement in hypogonadic males which comprises applying the device of claim 7 to the scrotum of a hypogonadic male and maintaining said system in testosterone transferring relationship to said scrotum for at least about 8 hours.

20. The method of claim 19 wherein said system is maintained in place for up to about 24 hours and is replaced with a fresh device on a daily basis for so long as testosterone replacement is desired.

21. A method for testosterone replacement in hypogonadal males which comprises applying a device according to claim 12 to the genitalia of a hypogonadal male and maintaining said device in testosterone transmitting relationship thereto for at least about 8 hours.

22. The method of claim 21 wherein said device is replaced with a fresh device on a daily basis for so long as testosterone replacement is desired.

23. A method for testosterone replacement in hypogonadic males which comprises applying the device of claim 12 to the scrotum of a hypogonadic male and maintaining said system in testosterone transferring relationship to said scrotum for at least about 8 hours.

24. The method of claim 23 wherein said system is maintained in place for up to about 24 hours and is replaced with a fresh device on a daily basis for so long as testosterone replacement is desired.

25. A method for testosterone replacement in human males which comprises applying a testosterone releasing delivery device comprising a testosterone containing polymeric matrix to the male genitalia and maintaining said device in testosterone transmitting relationship thereto for a least about 8 hours.

26. The method of claim 25 further comprising the steps of removing the used device and replacing it with a fresh device on a daily basis for so long as testosterone replacement is desired.

27. A method for testosterone replacement in human males which comprises applying a testosterone releasing delivery device comprising a testosterone containing polymeric matrix to the scrotum and maintaining said device in testosterone transmitting relationship thereto for a least about 8 hours.

34. The method of claim 27 further comprising the steps of removing the used device and replacing it with a fresh device on a daily basis for so long as testosterone replacement is desired.

28. A method for testosterone replacement in the human male which comprises applying a stretchable testosterone releasing delivery device to the male genitalia by non-elastically stretching the delivery device about the genitalia whereby the device conforms to and clings to the skin of the genitalia and maintaining said device in testosterone transmitting relationship thereto for a least 8 hours.

29. The method of claim 28 wherein the site of administration is the scrotum.

30. The method of claim 28 wherein the body contacting surface of said delivery device has a tack in the range of 100-300 g/cm² at 35°

C.

31. The method of claim 29 wherein the body contacting surface of said delivery device has a tack in the range of 100-300 g/cm² at 35°

C.

35. The method of claim 28 further comprising the steps of removing the used device and replacing it with a fresh device on a daily basis for so long as testosterone replacement is desired.

36. The method of claim 29 further comprising the steps of removing the used device and replacing it with a fresh device on a daily basis for so long as testosterone replacement is desired.

37. The method of claim 30 further comprising the steps of removing the used device and replacing it with a fresh device on a daily basis for so long as testosterone replacement is desired.

32. The method for testosterone replacement in human males whose testosterone blood levels are below those of normal males which comprises applying a testosterone releasing delivery device to the genitalia of a human male, maintaining said device in testosterone transmitting relationship to the genitalia during an administration period of at least about 8 hours, and delivering testosterone to the male from said delivery device at a varying rate over said administration period, said varying rate being selected to produce testosterone blood levels which approximate the circadian pattern of testosterone blood levels exhibited by a normal male.

33. The method of claim 32 wherein said site for the administration is the scrotum.

38. The method of claim 32 further comprising the steps of removing the used device and replacing it with a fresh device on a daily basis for so long as testosterone replacement is desired.

39. The method of claim 33 further comprising the steps of removing the used device and replacing it with a fresh device on a daily basis for so long as testosterone replacement is desired.