Dosage forms and layered deposition processes for fabricating dosage forms

• US 20050118246A1
• Filed: 10/29/2004
• Published: 06/02/2005
• Est. Priority Date: 10/31/2003
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Wong, Patrick S.L., Silber, B. Michael
• Application Number:
  US10/976,589
• Publication Number:
  US 20050118246A1
• Time in Patent Office: Days
• US Class Current: 424/449
• CPC Class Codes: A61F 2013/0296 for making transdermal patches (chemical processes excluded)
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• 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

Abstract

Disclosed are transdermal or transmucosal dosage forms which include a matrix and a drug where the total amount of drug present in the dosage form exceeds the solubility limit of the drug in the matrix. Also disclosed are transdermal or transmucosal dosage forms which include two or more drug-containing layers and one or more intervening hydrophilic layers where the two or more drug-containing layers being separated from one another by the one or more intervening hydrophilic layers. Methods for delaying release and delivery of an active from an active layer disposed in a transdermal or transmucosal dosage form are also disclosed, as well as methods for manufacturing transdermal or transmucosal dosage forms by providing a substrate and disposing at least one transdermal or transmucosal dosage form layer on the substrate using a printing process.

Claims

1. A transdermal or transmucosal dosage form comprising:

a matrix; and

a drug;

wherein the total amount of said drug present in said dosage form exceeds the solubility limit of said drug in said matrix.

2. A dosage form according to aspect 1, wherein said drug is dispersed in said matrix at a concentration greater than the solubility limit of the drug in the matrix.

3. A dosage form according to aspect 2, wherein said drug is substantially uniformly dispersed in said matrix.

4. A dosage form according to aspect 1, wherein said drug and said matrix are present as substantially discrete layers.

5. A dosage form according to aspect 1, wherein said dosage form further comprises a pressure sensitive adhesive layer on one surface of said dosage form.

6. A dosage form according to aspect 1, wherein said dosage form further comprises a backing layer on one surface of said dosage form.

7. A dosage form according to aspect 1, wherein said dosage form further comprises a pressure sensitive adhesive layer on one surface of said dosage form and a backing layer on an opposing surface of said dosage form.

8. A dosage form according to aspect 7, wherein said pressure sensitive adhesive layer comprises a mucoadhesive.

9. A dosage form according to aspect 1, wherein said dosage form further comprises a pressure sensitive adhesive layer on one surface of said dosage form and a release liner in contact with said pressure sensitive adhesive layer.

10. A dosage form according to aspect 1, wherein said dosage form further comprises one or more hydrophilic layers stratified with said drug and matrix.

11. A dosage form according to aspect 10, wherein said one or more hydrophilic layers comprise a dehydrated hydrogel.

12. A dosage form according to aspect 11, wherein the dehydrated hydrogel is a cross-linked poly(acrylic acid).

13. A dosage form according to aspect 11, wherein the dehydrated hydrogel is a hydroxyether cellulose.

14. A transdermal or transmucosal dosage form comprising:

two or more drug-containing layers; and

one or more intervening hydrophilic layers;

wherein said two or more drug-containing layers are separated from one another by said one or more intervening hydrophilic layers.

15. A dosage form according to aspect 14, wherein said one or more intervening hydrophilic layers comprises a dehydrated hydrogel.

16. A dosage form according to aspect 15, wherein said dehydrated hydrogel is a cross-linked poly(acrylic acid).

17. A dosage form according to aspect 15, wherein said dehydrated hydrogel is a hydroxyether cellulose.

18. A dosage form according to aspect 14, wherein said dosage form further comprises a pressure sensitive adhesive layer on one surface of said dosage form.

19. A dosage form according to aspect 14, wherein said dosage form further comprises a backing layer on one surface of said dosage form.

20. A dosage form according to aspect 14, wherein said dosage form further comprises a pressure sensitive adhesive layer on one surface of said dosage form and a backing layer on an opposing surface of said dosage form.

21. A dosage form according to aspect 20, wherein said pressure sensitive adhesive layer comprises a mucoadhesive.

22. A dosage form according to aspect 14, wherein said two or more drug-containing layers and said one or more intervening hydrophilic layers form a first layer set;

wherein said dosage form comprises a second layer set;

wherein said second layer set comprises two or more drug-containing layers and one or more intervening hydrophilic layers; and

wherein said second layer set'"'"'s two or more drug-containing layers are separated from one another by said second layer set'"'"'s one or more intervening hydrophilic layers.

23. A dosage form according to aspect 22, wherein each of said first layer set'"'"'s drug-containing layers is substantially aligned in a coplanar arrangement with each of said second layer set'"'"'s drug-containing layers and wherein each of said first layer set'"'"'s hydrophilic layers is substantially aligned in a coplanar arrangement with each of said second layer set'"'"'s hydrophilic layers.

24. A dosage form according to aspect 22, wherein each of said first layer set'"'"'s drug-containing layers is substantially aligned in a coplanar arrangement with each of said second layer set'"'"'s hydrophilic layers and wherein each of said first layer set'"'"'s hydrophilic layers is substantially aligned in a coplanar arrangement with each of said second layer set'"'"'s drug-containing layers.

25. A method for preparing a transdermal or transmucosal dosage form comprising a matrix and a drug dispersed in the matrix, wherein the total amount of the drug present in the dosage form exceeds the solubility limit of the drug in the matrix, said method comprising:

sequentially forming two or more layers of drug and two or more layers of matrix such that the amount of drug contained in the two or more layers of drug exceeds the solubility limit of the drug in the matrix.

26. A method according to aspect 25, wherein, subsequent to said forming, the drug becomes dispersed in the matrix.

27. A method according to aspect 25, wherein, subsequent to said forming, the drug becomes substantially uniformly dispersed in the matrix.

28. A method according to aspect 25, wherein, subsequent to said forming, said drug and said matrix remain as substantially discrete layers.

29. A method according to aspect 25, wherein at least one drug layer is formed by dispensing drops of a solution or dispersion containing the drug next to one another.

30. A method according to aspect 29, wherein the drops are dispensed using a single drop dispenser.

31. A method according to aspect 29, wherein the drops are dispensed by spraying.

32. A method according to aspect 25, wherein at least one drug layer is formed by microembossing.

33. A method according to aspect 25, wherein the drug layers and the matrix layers are sequentially formed over a substrate.

34. A method according to aspect 33, wherein the substrate is a backing layer.

35. A method according to aspect 34, wherein said method further comprises:

forming a pressure sensitive adhesive layer over the drug layers and the matrix layers.

36. A method according to aspect 33, wherein the substrate is a pressure sensitive adhesive layer.

37. A method according to aspect 36, wherein said method further comprises:

forming a backing layer over the drug layers and the matrix layers.

38. A method for delaying release of an active from an active layer disposed in a transdermal or transmucosal dosage form comprising, in addition to the active layer, an adhesive layer, said method comprising:

disposing one or more hydrophilic layers between the adhesive layer and the active layer.

39. A method according to aspect 38, wherein the one or more hydrophilic layers comprise a dehydrated hydrogel.

40. A method according to aspect 39, wherein said dehydrated hydrogel is a cross-linked poly(acrylic acid).

41. A method according to aspect 39, wherein said dehydrated hydrogel is a hydroxyether cellulose.

42. A method for delaying delivery of an active from an active layer disposed in a transdermal or transmucosal dosage form to a subject'"'"'s skin or mucosa, said method comprising:

disposing, in the dosage form, one or more hydrophilic layers between the active layer and the subject'"'"'s skin or mucosa.

43. A method according to aspect 42, wherein the one or more hydrophilic layers comprise a dehydrated hydrogel.

44. A method according to aspect 43, wherein said dehydrated hydrogel is a cross-linked poly(acrylic acid).

45. A method according to aspect 43, wherein said dehydrated hydrogel is a hydroxyether cellulose.

46. A method of manufacturing a transdermal or transmucosal dosage form, said method comprising:

providing a substrate; and

disposing at least one transdermal or transmucosal dosage form layer on the substrate using a printing process.

47. A method according to aspect 46, wherein the substrate comprises a backing layer.

48. A method according to aspect 46, wherein, the substrate comprises an adhesive layer.

49. A method according to aspect 46, wherein the substrate comprises a release liner.

50. A method according to aspect 46, wherein the substrate is release liner and wherein said disposing comprises disposing an adhesive layer on the release liner using a printing process.

51. A method according to aspect 46, wherein said disposing comprises disposing a drug layer on the substrate using a printing process.

52. A method according to aspect 46, wherein said disposing comprises disposing a patterned drug layer on the substrate using a printing process.

53. A method according to aspect 46, wherein the printing process is carried out using single drop dispensers.

54. A method according to aspect 46, wherein the printing process is carried out using multiple drop dispensers.

55. A method according to aspect 46, wherein the printing process is carried out by microembossing.

56. A method according to aspect 46, wherein the printing process is carried out by sequential adsorption of polyelectrolytes.