Polymeric compositions and dosage forms comprising the same

• US 20050196447A1
• Filed: 03/05/2004
• Published: 09/08/2005
• Est. Priority Date: 03/05/2004
• Status: Abandoned Application

• Current Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Original Assignee: McNeil-PPC Incorporated (Johnson & Johnson)
• Inventors: Lee, Der-Yang, Li, Shun Por, Huang, Hai Yong
• Application Number:
  US10/794,659
• Publication Number:
  US 20050196447A1
• 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
• CPC Class Codes: A61K 9/286 Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

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. At least a portion of the shell may be comprised of a polymeric composition containing film former, gelling agents, which can be dissolved in a multisolvent system comprised of water and an organic solvent.

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 the shell comprises a first shell portion which is semipermeable to a liquid medium and comprised of, based upon the total dry weight of the shell, from about 40 percent to about 99 percent of a water insoluble film forming polymer and from about 1 percent to about 30 percent of a gelling agent, 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.

2. The dosage form of claim 1, wherein the water insoluble film forming polymer is cellulose acetate and/or ethyl cellulose.

3. The dosage form of claim 2, wherein the gelling agent is selected from the group consisting of hydrocolloids, gelling starches, and derivatives, copolymers, and mixtures thereof.

4. The dosage form of claim 3, wherein the gelling agent is a hydrocolloid selected from the group consisting of carrageenan, gellan gum, agar, alginate, pectin, and derivatives, and mixtures thereof.

5. The dosage form of claim 1, wherein the shell is comprised of, based upon the total dry weight of the shell, from about 50 percent to about 80 percent of a water insoluble, film forming polymer, wherein the water insoluble, film forming polymer is cellulose acetate and/or ethyl cellulose, and from about 5 percent to about 10 percent of a carrageenan gelling agent.

6. The dosage form of claim 1, in which at least one of the first or second shell portions has at least one passageway therein extending from the surface of the shell portion, through the shell, and to at least the surface of the core.

7. The dosage form of claim 5, in which at least one of the first or second shell portions has at least one passageway therein extending to the core outer surface.

8. The dosage form of claim 1, in which the second shell portion is diffusible.

9. The dosage form of claim 5, in which the second shell portion is diffusible.

10. The dosage form of claim 1, in which the first shell portion has at least one passageway extending from the surface of the shell portion, through the shell, and to at least the surface of the core, and the second shell portion is impermeable to the liquid medium.

11. The dosage form of claim 5, in which the first shell portion has at least one passageway extending from the surface of the shell portion, through the shell, and to at least the surface of the core, and the second shell portion is impermeable to the liquid medium.

12. The dosage form of claim 1, in which the core and/or the shell comprises at least one active ingredient.

13. The dosage form of claim 5, in which the core and/or the shell comprises at least one active ingredient.

14. The dosage form of claim 1, 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.

15. The dosage form of claim 5, 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.

16. The dosage form of claim 1, 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.

17. The dosage form of claim 5, 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.

18. The dosage form of claim 1, in which the core comprises at least one active ingredient in a first core portion and/or a second core portion.

19. The dosage form of claim 5, in which the core comprises at least one active ingredient in a first core portion and/or a second core portion.

20. The dosage form of claim 1, wherein at least a portion of the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 0.5 percent to about 5 percent of a pore former selected from the group consisting of polyethylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, and copolymers and mixtures thereof.

21. The dosage form of claim 1 wherein at least a portion of the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 1 percent to about 30 percent of a plasticizer.

22. The dosage form of claim 21, wherein the plasticizer is selected from the group consisting of polyethylene glycol;

propylene glycol;

glycerin;

sorbitol;

triethyl citrate;

tribuyl citrate;

dibutyl sebecate;

vegetable oils;

polysorbates;

sodium lauryl sulfates;

dioctyl-sodium sulfosuccinates;

mono acetate of glycerol;

diacetate of glycerol;

triacetate of glycerol;

natural gums;

triacetin;

acetyltributyl citrate;

diethyloxalate;

diethylmalate;

diethyl fumarate;

diethylmalonate;

dioctylphthalate;

dibutylsuccinate;

glycerol tributyrate;

hydrogenated castor oil;

fatty acids;

glycerides; and

mixtures thereof.

23. The dosage form of claim 21, wherein the plasticizer is selected from the group consisting of triethyl citrate, dibutylsebacate, triacetin, and mixtures thereof.

24. The dosage form of claim 1, wherein the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 0.05 percent to about 5 percent of at least one of the following permeation modifying, water-soluble polymers:

polyalkylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, or hydroxyethylcellulose.

25. The dosage form of claim 5, wherein the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 0.05 percent to about 5 percent of at least one of the following permeation modifying, water-soluble polymers:

polyalkylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, or hydroxyethylcellulose.

26. The dosage form of claim 1, wherein the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 0.5 percent to about 5 percent of a pore former selected from the group consisting of polyethylene glycol, hydroxypropylmethylcellulose, or hydroxypropylcellulose.

27. 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 a liquid medium and is comprised of, based upon the total dry weight of the shell, from about 40 percent to about 99 percent of a water insoluble film forming polymer and from about 1 percent to about 30 percent of a gelling agent, 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 extending from the surface of the shell portion, through the shell, and to at least the surface of the core.

28. The dosage form of claim 27, wherein the shell is comprised of, based upon the total dry weight of the shell, from about 50 percent to about 80 percent of a water insoluble, film forming polymer, wherein the water insoluble, film forming polymer is cellulose acetate and/or ethyl cellulose, and from about 2 percent to about 10 percent of a carrageenan gelling agent.

29. The dosage form of claim 27, in which at least one of the first or second core portions comprises at least one active ingredient.

30. The dosage form of claim 28, in which at least one of the first or second core portions comprises at least one active ingredient.

31. The dosage form of claim 27, 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.

32. The dosage form of claim 28, 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.

33. The dosage form of claim 27, wherein at least a portion of the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 0.5 percent to about 5 percent of a pore former selected from the group consisting of polyethylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, and copolymers and mixtures thereof.

34. The dosage form of claim 27 wherein at least a portion of the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 1 percent to about 30 percent of a plasticizer.

35. The dosage form of claim 34, wherein the plasticizer is selected from the group consisting of polyethylene glycol;

propylene glycol;

glycerin;

sorbitol;

triethyl citrate;

tribuyl citrate;

dibutyl sebecate;

vegetable oils;

polysorbates;

sodium lauryl sulfates;

dioctyl-sodium sulfosuccinates;

mono acetate of glycerol;

diacetate of glycerol;

triacetate of glycerol;

natural gums;

triacetin;

acetyltributyl citrate;

diethyloxalate;

diethylmalate;

diethyl fumarate;

diethylmalonate;

dioctylphthalate;

dibutylsuccinate;

glycerol tributyrate;

hydrogenated castor oil;

fatty acids;

glycerides; and

or mixtures thereof.

36. The dosage form of claim 34, wherein the plasticizer is selected from the group consisting of triethyl citrate, dibutylsebacate, triacetin, and mixtures thereof.

37. The dosage form of claim 27, wherein at least a portion of the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 0.05 percent to about 5 percent of at least one of the following permeation modifying, water-soluble polymers:

polyalkylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, or hydroxyethylcellulose.

38. The dosage form of claim 27, wherein at least a portion of the first shell portion is further comprised of, based upon the total dry weight of the first shell portion, from about 0.5 percent to about 5 percent of a pore former selected from the group consisting of polyethylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, and copolymers and mixtures thereof.