Dosage form providing ascending release of liquid formulation

• US 20040091538A1
• Filed: 10/31/2003
• Published: 05/13/2004
• Est. Priority Date: 10/31/2002
• Status: Abandoned Application

• Current Assignee: Crystal Pollock-Dove, Liang Dong, Patrick S.L. Wong, Si-Hong Yum
• Original Assignee: Crystal Pollock-Dove, Liang Dong, Patrick S.L. Wong, Si-Hong Yum
• Inventors: Dong, Liang, Pollock-Dove, Crystal, Wong, Patrick S. L., Yum, Si-Hong
• Application Number:
  US10/700,941
• Publication Number:
  US 20040091538A1
• Time in Patent Office: Days
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

The present invention includes a dosage form that releases a liquid active agent formulation over a period of time at an ascending rate. The dosage form of the present invention includes a capsule or other reservoir capable of containing a liquid active agent formulation, a driving means for expelling the liquid active agent formulation from the capsule over an extended period of time and a rate altering means for increasing the rate at which the driving means expels liquid active agent formulation from the capsule. The present invention also includes a method of manufacturing a controlled release dosage form providing the release of liquid active agent formulation at an ascending rate. The method of the present invention includes providing a capsule or reservoir suitable for containing a liquid active agent formulation, filling the capsule with a liquid active agent formulation, providing the capsule with a driving means for expelling the liquid active agent formulation from the capsule to an environment of use, and providing a rate altering means for increasing the rate at which the driving means expels the liquid active agent formulation.

Claims

1. A dosage form comprising:

a reservoir;

a liquid active agent formulation contained within the reservoir;

an osmotic composition a semipermeable membrane;

an ascending release material adjacent to the semipermeable membrane, the ascending release material exhibiting a permeability that increases upon exposure to aqueous fluid; and

an exit orifice.

2. The dosage form of claim 1, wherein the ascending release material comprises a polymer.

3. The dosage form of claim 1, wherein the ascending release material comprises a hydrophobic polymer and a hydrophilic polymer.

4. The dosage form of claim 1, wherein the ascending release material comprises a hydrophobic polymer and a hydrophilic polymer, wherein the hydrophilic polymer is water swellable.

5. The dosage form of claim 3, wherein the hydrophobic polymer comprises about 50 wt % to about 80 wt % of the ascending release material and hydrophilic polymer comprises about 20 wt % to about 50 wt % of the ascending release material.

6. The dosage form of claim 3, wherein the hydrophobic polymer comprises about 60 wt % to about 70 wt % of the ascending release material and the hydrophilic polymer comprises about 30 wt % to about 40 wt % of the ascending release material.

7. The dosage form of claim 1, wherein the ascending release material is formulated such that the ascending release material exhibits a first permeability before exposure to an aqueous fluid and a second permeability after exposure the aqueous fluid, wherein the second permeability increases as the ascending release material is exposed to the aqueous fluid over time.

8. The dosage form of claim 1, wherein the reservoir, the osmotic composition, the semipermeable membrane, and the ascending release material adjacent to the semipermeable membrane are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of at least two hours.

9. The dosage form of claim 1, wherein the reservoir, the osmotic composition, the semipermeable membrane, and the ascending release material adjacent to the semipermeable membrane are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of about 2 to about 24 hours.

10. The dosage form of claim 1, wherein the reservoir, the osmotic composition, the semipermeable membrane, and the ascending release material adjacent to the semipermeable membrane are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of about 4 to about 12 hours.

11. The dosage form of claim 1, wherein the ascending release material comprises a hydrophobic acrylic polymer and a hydrophilic vinyl polymer.

12. The dosage form of claim 11, wherein the hydrophobic acrylic polymer comprises a 85/15 wt/wt blend of Eudragit NE/Eudragit FS and the hydrophilic vinyl polymer comprises a cross linked polyvinylpyrrolidone.

13. The dosage form of claim 1, wherein the ascending release material comprises a hydrophobic polymer and a hydrophilic polymer, and the hydrophobic polymer comprises one or more material selected from the group consisting of polystyrene, polyamides, polyvinyl acetate, poly-methylmethacrylate, ethyl acrylate methyl methacrylate copolymer, ethyl acrylate methyl methacrylate copolymer, poly(butyl methacrylate (2-dimethyl aminoethyl)methacrylate, methyl methacrylate), and methacrylic acid methylmethacrylate copolymer.

14. The dosage form of claim 1, wherein the ascending release material comprises a hydrophobic polymer and a hydrophilic polymer, and the hydrophilic polymer comprises one or more material selected from the group consisting of low substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl methylcellulose, polyvinyl acetate polyvinyl pyrrolidone copolymer, gelatin, starch, polyethylene glycol polyvinyl alcohol copolymer, carrageenan, algin, agar, gum acacia, gum karyara, carob bean gum, gum tragacanth, gum ghatti guar gum, caseinates, cellulose acetate with an acetyl content of less than 20 wt %, sodium carboxymethyl cellulose, potassium carboxy methyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyethylene glycol graph copolymers, cellulose acetate phthalate, hydroxypropyl methycellulose phthalate, and hydroxypropyl methyl cellulose acetate succinate.

15. A dosage form comprising:

a capsule;

a liquid active agent formulation contained within the capsule;

an osmotic composition;

a semipermeable membrane;

an ascending release material adjacent to the semipermeable membrane, the ascending release material exhibiting a permeability that increases upon exposure to aqueous fluid; and

an exit orifice.

20. The dosage form of claim 15, wherein the capsule comprises a gelatin material.

21. The dosage form of claim 15, wherein the osmotic composition is formed of a tableted composition and is positioned at least partially within the capsule, the ascending release material is formed over the capsule and the semipermeable membrane is formed over the ascending release material.

22. The dosage form of claim 21, wherein the osmotic composition comprises a bi-layer tableted composition having an osmotic composition and a barrier layer.

16. A dosage form comprising:

a capsule;

a liquid active agent formulation contained within the capsule;

an osmotic composition formed around the capsule;

an ascending release material exhibiting a permeability that increases upon exposure to aqueous fluid formed over the osmotic composition;

a semipermeable membrane formed adjacent to the ascending release material; and

an exit orifice.

17. The dosage form of claim 16, wherein a barrier layer is formed around the capsule and the osmotic composition is formed around the barrier layer.

18. A dosage form comprising:

a capsule;

a liquid active agent formulation contained within the capsule;

an osmotic composition formed around the capsule;

a semipermeable membrane formed over the osmotic composition;

an ascending release material exhibiting a permeability that increases upon exposure to aqueous fluid formed over the semipermeable membrane; and

an exit orifice.

19. The dosage form of claim 18, wherein a barrier layer is formed around the capsule and the osmotic composition is formed around the barrier layer.

23. A dosage form comprising:

a capsule;

a liquid active agent formulation contained within the capsule;

an osmotic composition formed around the capsule;

an ascending release material exhibiting a permeability that increases upon exposure to aqueous fluid, the ascending release material being formed over the osmotic composition and comprising a blend of polymers including a hydrophobic polymer and a hydrophilic polymer;

a semipermeable membrane formed adjacent to the ascending release material; and

an exit orifice.

24. The dosage form of claim 23, wherein the ascending release material comprises a water swellable hydrophilic polymer.

25. The dosage form of claim 23, wherein the hydrophobic polymer comprises about 50 wt % to about 80 wt % of the ascending release material and the hydrophilic polymer comprises about 20 wt % to about 50 wt % of the ascending release material.

26. The dosage form of claim 23, wherein the hydrophobic polymer comprises about 60 wt % to about 70 wt % of the ascending release material and the hydrophilic polymer comprises about 30 wt % to about 40 wt % of the ascending release material.

27. The dosage form of claim 23, wherein the ascending release material is formulated such that the ascending release material exhibits a first permeability before exposure to an aqueous fluid and a second permeability after exposure to the aqueous fluid, wherein the second permeability increases as the ascending release material is exposed to the aqueous fluid over time.

28. The dosage form of claim 23, wherein the capsule, the osmotic composition, the semipermeable membrane, and the ascending release material are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of at least two hours.

29. The dosage form of claim 23, wherein the capsule, the osmotic composition, the semipermeable membrane, and the ascending release material are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of about 2 to about 24 hours.

30. The dosage form of claim 23, wherein the a capsule, the osmotic composition, the semipermeable membrane, and the ascending release material are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of about 4 to about 12 hours.

31. The dosage form of claim 23, wherein the ascending release material comprises a hydrophobic acrylic polymer and a hydrophilic vinyl polymer.

32. The dosage form of claim 31, wherein the hydrophobic acrylic polymer comprises a 85/15 wt/wt blend of Eudragit NE/Eudragit FS and the hydrophilic vinyl polymer comprises a cross linked polyvinylpyrrolidone.

33. The dosage form of claim 23, wherein the hydrophobic polymer comprises one or more material selected from the group consisting of polystyrene, polyamides, polyvinyl acetate, poly-methylmethacrylate, ethyl acrylate methyl methacrylate copolymer, ethyl acrylate methyl methacrylate copolymer, poly(butyl methacrylate (2-dimethyl aminoethyl)methacrylate, methyl methacrylate), and methacrylic acid methylmethacrylate copolymer.

34. The dosage form of claim 23, wherein the hydrophilic polymer comprises one or more material selected from the group consisting of low substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl methylcellulose, polyvinyl acetate polyvinyl pyrrolidone copolymer, gelatin, starch, polyethylene glycol polyvinyl alcohol copolymer, carrageenan, algin, agar, gum acacia, gum karyara, carob bean gum, gum tragacanth, gum ghatti guar gum, caseinates, cellulose acetate with an acetyl content of less than 20 wt %, sodium carboxymethyl cellulose, potassium carboxy methyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyethylene glycol graph copolymers, cellulose acetate phthalate, hydroxypropyl methycellulose phthalate, and hydroxypropyl methyl cellulose acetate succinate.

35. A dosage form comprising:

a capsule body;

a liquid active agent formulation contained within the capsule body;

a tableted osmotic composition positioned at least partially within the capsule;

an ascending release material exhibiting a permeability that increases upon exposure to aqueous fluid, the ascending release material being formed over the osmotic composition and comprising a blend of polymers including a hydrophobic polymer and a hydrophilic polymer;

a semipermeable membrane formed adjacent to the ascending release material; and

an exit orifice.

36. The dosage form of claim 35, wherein the osmotic composition comprises a bi-layer tableted composition having an osmotic composition and a barrier layer.

37. The dosage form of claim 35, further comprising a water impermeable subcoat formed over an outer surface of the capsule body.

38. The dosage form of claim 37, wherein the water impermeable subcoat comprises a latex material.

39. The dosage form of claim 35, wherein the ascending release material comprises a water swellable hydrophilic polymer.

40. The dosage form of claim 35, wherein the hydrophobic polymer comprises about 50 wt % to about 80 wt % of the ascending release material and the hydrophilic polymer comprises about 20 wt % to about 50 wt % of the ascending release material.

41. The dosage form of claim 35, wherein the hydrophobic polymer comprises about 60 wt % to about 70 wt % of the ascending release material and the hydrophilic polymer comprises about 30 wt % to about 40 wt % of the ascending release material.

42. The dosage form of claim 35, wherein the ascending release material is formulated such that the ascending release material exhibits a first permeability before exposure to an aqueous fluid and a second permeability after exposure to the aqueous fluid, wherein the second permeability increases as the ascending release material is exposed to the aqueous fluid over time.

43. The dosage form of claim 35, wherein the capsule body, the osmotic composition, the semipermeable membrane, and the ascending release material are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of at least two hours.

44. The dosage form of claim 35, wherein the capsule body, the osmotic composition, the semipermeable membrane, and the ascending release material are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of about 2 to about 24 hours.

45. The dosage form of claim 35, wherein the a capsule body, the osmotic composition, the semipermeable membrane, and the ascending release material are chosen and configured such that the dosage form provides controlled, ascending release of the liquid active agent formulation over a period of about 4 to about 12 hours.

46. The dosage form of claim 35, wherein the ascending release material comprises a hydrophobic acrylic polymer and a hydrophilic vinyl polymer.

47. The dosage form of claim 35, wherein the hydrophobic acrylic polymer comprises a 85/15 wt/wt blend of Eudragit NE/Eudragit FS and the hydrophilic vinyl polymer comprises a cross linked polyvinylpyrrolidone.

48. The dosage form of claim 35, wherein the hydrophobic polymer comprises one or more material selected from the group consisting of polystyrene, polyamides, polyvinyl acetate, poly-methylmethacrylate, ethyl acrylate methyl methacrylate copolymer, ethyl acrylate methyl methacrylate copolymer, poly(butyl methacrylate (2-dimethyl aminoethyl)methacrylate, methyl methacrylate), and methacrylic acid methylmethacrylate copolymer.

49. The dosage form of claim 35, wherein the hydrophilic polymer comprises one or more material selected from the group consisting of low substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl methylcellulose, polyvinyl acetate polyvinyl pyrrolidone copolymer, gelatin, starch, polyethylene glycol polyvinyl alcohol copolymer, carrageenan, algin, agar, gum acacia, gum karyara, carob bean gum, gum tragacanth, gum ghatti guar gum, caseinates, cellulose acetate with an acetyl content of less than 20 wt %, sodium carboxymethyl cellulose, potassium carboxy methyl cellulose, polyvinyl alcohol, polyvinyl alcohol polyethylene glycol graph copolymers, cellulose acetate phthalate, hydroxypropyl methycellulose phthalate, and hydroxypropyl methyl cellulose acetate succinate.

50. A method for manufacturing a dosage form providing the ascending release of an liquid active agent formulation, the method comprising:

providing a reservoir;

loading a liquid active agent formulation within the reservoir;

operatively associating an osmotic composition with the reservoir;

forming an ascending release material over at least a portion of the dosage form; and

forming a semipermeable membrane adjacent said ascending release material.