Modified release dosage forms

• US 20030232082A1
• Filed: 03/21/2003
• Published: 12/18/2003
• Est. Priority Date: 09/28/2001
• Status: Abandoned Application

• Current Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Original Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Inventors: Sowden, Harry S., Lee, Der-Yang, Li, Shun-Por, Wynn, David, McNally, Gerard P., Parikh, Narendra, McTeigue, Daniel
• Application Number:
  US10/393,638
• Publication Number:
  US 20030232082A1
• Time in Patent Office: Days
• US Class Current: 424/473
• CPC Class Codes: A23G 1/54 Composite products, e.g. layered laminated, coated, filled
• CPC Class Codes: A23G 3/0029 Moulding processes for hollow products, e.g. opened shell
• CPC Class Codes: A23G 3/04 Sugar-cookers
• CPC Class Codes: A23G 3/368 containing vitamins, antibiotics
• CPC Class Codes: A23G 3/54 Composite products, e.g. layered, coated, filled
• CPC Class Codes: A23L 29/30 containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin products from apiculture A23L21/20; artificial sweetening agents A23L27/30
• CPC Class Codes: A61J 3/005 Coating of tablets or the like coating of sweetmeats or confectionery A23G3/20; coating of granules in general B01J2/006
• CPC Class Codes: A61J 3/06 into the form of pills, lozenges or dragees
• CPC Class Codes: A61J 3/10 into the form of compressed tablets tablet presses B30B11/00
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2068 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/2013
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2095 : Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/282 : Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/2826 : Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
• CPC Class Codes: A61K 9/284 : obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/286 : Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61K 9/2873 : Proteins, e.g. gelatin
• CPC Class Codes: A61K 9/2886 : having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/2893 : Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61K 9/5084 : Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B30B 11/08 : co-operating with moulds carried by a turntable
• CPC Class Codes: B30B 11/34 : for coating articles, e.g. tablets
• CPC Class Codes: B30B 15/302 : Feeding material in particulate or plastic state to moulding presses
• CPC Class Codes: Y10T 428/1352 : Polymer or resin containing [i.e., natural or synthetic]

Abstract

A dosage form comprises: (a) at least one active ingredient; (b) a core having an outer surface; and (c) a shell which resides upon at least a portion of the core outer surface, wherein at least a portion of the shell is semipermeable, such that the liquid medium diffuses through the semipermeable shell or shell portion to the core due to osmosis. The shell also provides for delivery of the active ingredient to a liquid medium outside the shell after contacting of the dosage form with the liquid medium. The dosage form delivers one or more active ingredients in a controlled manner upon contacting of the dosage form with a liquid medium. The dosage form may be employed to provide a burst release of the active ingredient, or to provide release of the active ingredient at an ascending release rate over an extended time period upon contacting of the dosage form with a liquid medium.

Claims

1. A dosage form comprising:

(a) at least one active ingredient;

(b) a core having an outer surface; and

(c) a shell which resides upon at least a portion of the core outer surface, wherein at least a portion of the shell is semipermeable, at least about 30% of the cross-sectional area of the semipermeable shell portion is non-striated, and the shell comprises means for providing the active ingredient to a liquid medium outside the shell after contacting of the dosage form with the liquid medium.

2. The dosage form of claim 1, in which substantially all of the shell is semipermeable, and the shell additionally comprises at least one passageway therein extending to the core outer surface.

3. The dosage form of claim 1, in which at least about 50% of the cross sectional area of the shell is non-striated.

4. The dosage form of claim 1, in which at least about 80% of the cross sectional area of the shell is non-striated.

5. The dosage form of claim 1, in which the core comprises at least one active ingredient.

6. The dosage form of claim 1, in which the shell comprises at least one active ingredient.

7. The dosage form of claim 1, in which the core and the shell each comprise at least one active ingredient.

8. The dosage form of claim 1, in which the core comprises an osmagent.

9. The dosage form of claim 1, in which the core comprises a first core portion and a second core portion.

10. The dosage form of claim 9, in which the shell comprises a plurality of passageways therein extending to the core.

35. The dosage form of any of claims 1, 11, 25, 28 or 30, wherein the providing of at least one active ingredient follows substantially zero-order kinetics over a specified time interval.

36. The dosage form of any of claims 1, 11, 25, 28 or 30, wherein the providing of at least one active ingredient follows square-root-of-time kinetics over a specified time interval.

37. The dosage form of any of claims 1, 11, 25, 28 or 30, wherein the providing of at least one active ingredient follows substantially first-order kinetics over a specified time interval.

40. The dosage form of any of claims 1, 11, 25, 28 or 30, in which the release rate of at least one active ingredient is non-constant.

41. The dosage form of any of claims 1, 11, 25, 28 or 30, in which the release of at least one dose of at least one active ingredient is a burst release.

42. The dosage form of any of claims 1, 11, 25, 28 or 30, in which the release rate of at least one active ingredient is an ascending release rate.

43. The dosage form of any of claim 1, 11, 25, 28, or 30, which provides an ascending blood level PK profile for at least one active ingredient after administration to a mammal.

44. The dosage form of any of claims 1, 11, 25, 28 or 30, in which the shell contains greater than 90 mg of at least one active ingredient.

11. A dosage form comprising:

(a) at least one active ingredient;

(b) a core having an outer surface; and

(c) a shell which resides upon at least a portion of the core outer surface,

wherein the shell comprises a first shell portion which is semipermeable to the liquid medium, and a second shell portion which is compositionally different than the first shell portion, the first and second shell portions each are substantially in contact with the core outer surface, and the shell comprises means for providing the active ingredient to a liquid medium outside the shell after contacting of the dosage form with the liquid medium.

12. The dosage form of claim 11, in which at least one of the first or second shell portions has at least one passageway therein extending to the core outer surface.

13. The dosage form of claim 11, in which the second shell portion is diffusible.

14. The dosage form of claim 11, in which the first shell portion has at least one passageway therein extending to the core, and the second shell portion is impermeable to the liquid medium.

15. The dosage form of claim 11, in which the second shell portion has at least one passageway therein extending to the core.

16. The dosage form of claim 11, in which the core comprises at least one active ingredient.

17. The dosage form of claim 11, in which the first shell portion comprises at least one active ingredient.

18. The dosage form of claim 11, in which the second shell portion comprises at least one active ingredient.

19. The dosage form of claim 11, in which the core, the first shell portion and the second shell portion each comprises at least one active ingredient.

20. The dosage form of claim 11, in which the first shell portion has a first thickness, and the second shell portion has a second thickness which is different than the first shell portion thickness.

21. The dosage form of claim 11, in which the first shell portion has a first thickness, and the second shell portion has a second thickness which is substantially the same as the first shell portion thickness.

22. The dosage form of claim 11, in which the core comprises a first core portion and a second core portion.

23. The dosage form of claim 22, in which at least one of the first or second core portions comprises at least one active ingredient.

24. The dosage form of claim 22, in which the first core portion comprises a first active ingredient and the second core portion comprises a second active ingredient which may be the same or different than the first active ingredient.

38. The dosage form of any of claims 9, 22, 25 or 30, wherein at least one of the first or second core portions functions as an eroding matrix.

39. The dosage form of claim 38, wherein the eroding matrix core portion comprises a release-modifying compressible or moldable excipient selected from swellable erodible hydrophilic agents, pH-dependent polymers, and combinations thereof.

25. A dosage form comprising:

(a) at least one active ingredient;

(b) a core having an outer surface, a first core portion, a second core portion, and a third core portion located between the first and second core portions, wherein the third core portion comprises an osmopolymer; and

(c) a shell which resides upon at least a portion of the core outer surface, in which the shell comprises a first shell portion which is semipermeable to the liquid medium, and a second shell portion which is compositionally different than the first shell portion, the first and second shell portions each are substantially in contact with the core outer surface, and at least one of the first or second shell portions has at least one passageway therein extending to the core outer surface.

26. The dosage form of claim 25, in which at least one of the first or second core portions comprises at least one active ingredient.

27. The dosage form of claim 25, in which the first core portion comprises a first active ingredient and the second core portion comprises a second active ingredient which may be the same or different than the first active ingredient.

28. A dosage form comprising:

(a) at least one active ingredient;

(b) a core having an outer surface; and

(c) a shell which resides upon at least a portion of the core outer surface, in which the shell comprises a first shell portion which is semipermeable to the liquid medium, and a second shell portion which is compositionally different than the first shell portion, the first and second shell portions each are substantially in contact with the core outer surface, and the shell and core have a continuous cavity therein defining an interior surface, wherein neither the first shell portion nor the second shell portion extend substantially upon the interior surface.

29. The dosage form of claim 28, in which the core comprises at least one active ingredient.

33. The dosage form of claims 28 or 30, in which the core erodes upon contacting of the interior surface with a liquid medium.

34. The dosage form of claims 28 or 30, in which the diameter of the continuous cavity is in the range of about 15 to about 90 percent of the thickness of the dosage form.

30. A dosage form comprising:

(a) at least one active ingredient;

(b) a core having an outer surface, a first core portion, a second core portion, and a third core portion located between the first and second core portions, wherein the third core portion comprises a osmopolymer; and

(c) a shell which resides upon at least a portion of the core outer surface, in which the shell comprises a first shell portion which is semipermeable to the liquid medium, and a second shell portion which is compositionally different than the first shell portion, the first and second shell portions each are substantially in contact with the core outer surface, and the shell and core have a continuous cavity therein defining an interior surface, wherein neither the first shell portion nor the second shell portion extend substantially upon the interior surface.

31. The dosage form of claim 30, in which at least one of the first or second core portions comprises at least one active ingredient.

32. The dosage form of claim 30, in which the first core portion comprises a first active ingredient and the second core portion comprises a second active ingredient which may be the same or different than the first active ingredient.