Polymeric compositions and dosage forms comprising the same

• US 20050196446A1
• 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:
  US10/794,449
• Publication Number:
  US 20050196446A1
• Time in Patent Office: Days
• US Class Current: 424/473
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• 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 at least a portion of the shell is semipermeable 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 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 comprised of at least one of the following:

cellulose esters, cellulose ethers, cellulose ester-ethers, polyvinyl alcohols, polyvinyl acetate, polycaprolactones, polyacrylate, polymethacrylate, or derivatives or copolymers thereof.

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

4. The dosage form of claim 3, wherein the gelling agent is comprised of at least one of the following:

hydrocolloids, gelling starches, or derivatives or copolymers thereof.

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

6. 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 2 percent to about 10 percent of a carrageenan gelling agent.

7. The dosage form of claim 6, in which substantially all of the shell is semipermeable, and said means for providing the active ingredient to a liquid medium outside the shell after contacting of the dosage form with the liquid medium comprises one or more passageways extending from the surface of the shell, through the shell, and to at least the surface of the core.

8. The dosage form of claim 1, in which said means for providing the active ingredient to a liquid medium outside the shell after contacting of the dosage form with the liquid medium comprises one or more passageways extending from the surface of the shell, through the shell, and to at least the surface of the core.

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

10. The dosage form of claim 1, further comprising an overcoating on at least a portion of the shell.

11. The dosage form of claim 10, in which the overcoating is comprised of at least one active ingredient.

12. The dosage form of claim 1, in which the core comprises an osmagent and/or an osmopolymer.

13. The dosage form of claim 6, in which the core comprises an osmagent and/or an osmopolymer.

14. The dosage form of claim 13, in which the core comprises, based upon the total weight of the core, from about 0.01 percent to about 40 percent of an osmagent selected from the group consisting of sodium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, lithium sulfate, potassium hydrogen phosphate, mannitol, urea, inositol, magnesium succinate, tartaric acid, carbohydrate, and mixtures thereof.

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

16. The dosage form of claim 1, in which the shell comprises a plurality of passageways therein extending to the core.

17. The dosage form of claim 6, in which the shell comprises a plurality of passageways therein extending to the core.

18. The dosage form of claim 1 wherein at least a portion of the shell is further comprised of, based upon the total dry weight of the shell, 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.

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

20. The dosage form of claim 19, 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.

21. The dosage form of claim 19, wherein the plasticizer is selected from the group consisting of triethyl citrate, dibutylsebacate, triacetin, and mixtures thereof.

22. The dosage form of claim 1, wherein at least a portion of the shell is further comprised of, based upon the total dry weight of the shell, 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.

23. The dosage form of claim 6, wherein at least a portion of the shell is further comprised of, based upon the total dry weight of the shell, 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.

24. The dosage form of claim 1, wherein at least a portion of the shell is further comprised of, based upon the total dry weight of the shell, 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.

25. The dosage form of claim 6, wherein at least a portion of the shell is further comprised of, based upon the total dry weight of the shell, 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.

26. The dosage form of claim 7, wherein the active ingredient is released from the dosage form via substantially zero-order kinetics.

27. The dosage form of claim 1, wherein the semipermeable shell portion possesses a hydrated tensile strength of at least about 500 psi.

28. The dosage form of claim 1, wherein the semipermeable shell portion has a thickness of from about 50 microns to about 500 microns.