Oral osmotic dosage form having a high flux membrane

• US 20060165798A1
• Filed: 01/27/2006
• Published: 07/27/2006
• Est. Priority Date: 01/27/2005
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Li, Shu, Edgren, David E., Bhatti, Gurdish K., Skluzacek, Robert
• Application Number:
  US11/341,251
• Publication Number:
  US 20060165798A1
• 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

Disclosed are oral osmotic dosage forms and methods wherein a semi-permeable membrane of the oral osmotic dosage form includes from about 23 wt % to about 50 wt % of a flux enhancer and from about 0.01 wt % to about 5 wt % of antioxidant, based on the total dry weight of the semi-permeable membrane. Such compositions provide high flux membranes with improved mechanical and transport stability during storage on the shelf.

Claims

1. An oral osmotic dosage form comprising:

a core that comprises a drug layer;

a semi-permeable membrane surrounding the core; and

at least one exit port through the semi-permeable membrane;

wherein the semi-permeable membrane comprises from about 23 wt % to about 50 wt % of a flux enhancer and from about 0.01 wt % to about 5 wt % of antioxidant, based on the total dry weight of the semi-permeable membrane.

2. The oral osmotic dosage form of claim 1, wherein the oral osmotic dosage form comprises an elementary osmotic pump dosage form.

3. The oral osmotic dosage form of claim 1, further comprising a push layer located within the semi-permeable membrane at a point distant from the exit port.

4. The oral osmotic dosage form of claim 1, wherein the drug layer comprises a liquid drug formulation.

5. The oral osmotic dosage form of claim 1, wherein the antioxidant comprises butylated hydroxyanisol, butylated hydroxytoluene, butylated hydroxymethylphenol, teriary butylhydroquinone, tocopherols, phospholipids, lecithin, editic acid, ascorbic acid, isoascorbic acid, fumaric acid, malic acid, ascorbic acid palmitate, gallic acid, propyl gallate, sodium ascorbate, sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, sodium formaldehyde sulfoxylate, sulfur dioxide, thioglycerol, thioglycolic acid, cysteine hydrochloride, acetylcysteine, ascorbyl palmitate, hydroquinone, nordihydroguaiaretic acid. Other antioxidants include phenols, bisphenols, polyphenols, hydroquinone derivatives, phenyl phosphites, phenyl thioesters, phenyl amines, phenylene diamines, diphenlamines, tetrakis(methylene 3-(3′

,5′

-di-t-butyl-4′

hydroxyphenyl)propionate)methane, tris(2,4-di-tert-butylphenyl) phosphite, 2,4-bis(n-octylthio)-6-(4-hydroxy-3,5-di-tert-butylanilino)-1,3,5-triazine, N′

,N′

-hexamethylene bis (3,5-di-tert-butyl-4-hydroxy-hydrocinnamamide), o,o-di-n-octadecyl-3-5-di-tert-butyl-4-hydroxybenzyl phosphonate, octadecyl 3-(3′

,5′

-di-tert-butyl-4′

-hydroxyphenyl) proprionate, thiodiethylene bis-(3,5-di-tert-butyl-4-hydroxy) hydrocinnamate, octylated diphenylamine, 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene, 2,6-di-tert-butyl-4-n-butylphenol, 4,4′

methylenebis (2,6-di-tert-butylphenol), 2,6-di-tert-butyl-α

-dimethylamino-p-cresol, 2,6-di-tert-butyl-4-ethylphenol, or combinations of the above.

6. The oral osmotic dosage form of claim 1, wherein the semi-permeable membrane comprises from about 0.01 wt % to about 3 wt % of the antioxidant, based on the total dry weight of the semi-permeable membrane.

7. The oral osmotic dosage form of claim 6, wherein the semi-permeable membrane comprises from about 0.01 wt % to about 1 wt % of the antioxidant, based on the total dry weight of the semi-permeable membrane.

8. A method of making an oral osmotic dosage form comprising:

providing a semi-permeable membrane that comprises from about 23 wt % to about 50 wt % of a flux enhancer and from about 0.01 wt % to about 5 wt % of antioxidant, based on the total dry weight of the semi-permeable membrane;

coating the semi-permeable membrane on a core that comprises a drug layer; and

forming at least one exit port through the semipermeable membrane.

9. The method of claim 8, wherein the oral osmotic dosage form comprises an elementary osmotic pump dosage form.

10. The method of claim 8, wherein the core further comprises a push layer.

11. The method of claim 8, wherein the drug layer comprises a liquid drug formulation located within the semi-permeable membrane at a point distant from the exit port.

12. The method of claim 8, wherein the antioxidant comprises butylated hydroxyanisol, butylated hydroxytoluene, butylated hydroxymethylphenol, teriary butylhydroquinone, tocopherols, phospholipids, lecithin, editic acid, ascorbic acid, isoascorbic acid, fumaric acid, malic acid, ascorbic acid palmitate, gallic acid, propyl gallate, sodium ascorbate, sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, sodium formaldehyde sulfoxylate, sulfur dioxide, thioglycerol, thioglycolic acid, cysteine hydrochloride, acetylcysteine, ascorbyl palmitate, hydroquinone, nordihydroguaiaretic acid. Other antioxidants include phenols, bisphenols, polyphenols, hydroquinone derivatives, phenyl phosphites, phenyl thioesters, phenyl amines, phenylene diamines, diphenlamines, tetrakis(methylene 3-(3′

,5′

-di-t-butyl-4′

hydroxyphenyl)propionate)methane, tris(2,4-di-tert-butylphenyl)phosphite, 2,4-bis(n-octylthio)-6-(4-hydroxy-3,5-di-tert-butylanilino)-1,3,5-triazine, N′

,N′

-hexamethylene bis (3,5-di-tert-butyl-4-hydroxy-hydrocinnamamide), o,o-di-n-octadecyl-3-5-di-tert-butyl-4-hydroxybenzyl phosphonate, octadecyl 3-(3′

,5′

-di-tert-butyl-4′

-hydroxyphenyl) proprionate, thiodiethylene bis-(3,5-di-tert-butyl-4-hydroxy) hydrocinnamate, octylated diphenylamine, 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene, 2,6-di-tert-butyl-4-n-butylphenol, 4,4′

methylenebis (2,6-di-tert-butylphenol), 2,6-di-tert-butyl-α

-dimethylamino-p-cresol, 2,6-di-tert-butyl-4-ethylphenol, or combinations of the above.

13. The method of claim 8, wherein the semi-permeable membrane comprises from about 0.01 wt % to about 3 wt % of the antioxidant, based on the total dry weight of the semi-permeable membrane.

14. The method of claim 13, wherein the semi-permeable membrane comprises from about 0.01 wt % to about 1 wt % of the antioxidant, based on the total dry weight of the semi-permeable membrane.

15. An oral osmotic dosage form made according to the method of claim 8.

16. A method comprising:

providing a oral osmotic dosage form that comprises a semi-permeable membrane that comprises from about 23 wt % to about 50 wt % of a flux enhancer and from about 0.01 wt % to about 5 wt % of antioxidant, based on the total dry weight of the semi-permeable membrane; and

administering the oral osmotic dosage form to a patient.

17. The method of claim 16, wherein the oral osmotic dosage form comprises an elementary osmotic pump dosage form.

18. The method of claim 16, further comprising a push layer located within the semi-permeable membrane.

19. The method of claim 16, wherein the oral osmotic dosage form comprises a liquid drug formulation.

20. The method of claim 16, wherein the antioxidant comprises butylated hydroxyanisol, butylated hydroxytoluene, butylated hydroxymethylphenol, teriary butylhydroquinone, tocopherols, phospholipids, lecithin, editic acid, ascorbic acid, isoascorbic acid, fumaric acid, malic acid, ascorbic acid palmitate, gallic acid, propyl gallate, sodium ascorbate, sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, sodium formaldehyde sulfoxylate, sulfur dioxide, thioglycerol, thioglycolic acid, cysteine hydrochloride, acetylcysteine, ascorbyl palmitate, hydroquinone, nordihydroguaiaretic acid. Other antioxidants include phenols, bisphenols, polyphenols, hydroquinone derivatives, phenyl phosphites, phenyl thioesters, phenyl amines, phenylene diamines, diphenlamines, tetrakis(methylene 3-(3′

,5′

-di-t-butyl-4′

hydroxyphenyl)propionate)methane, tris(2,4-di-tert-butylphenyl)phosphite, 2,4-bis(n-octylthio)-6-(4-hydroxy-3, 5-di-tert-butylanilino)-1,3,5-triazine, N′

,N′

-hexamethylene bis (3,5-di-tert-butyl-4-hydroxy-hydrocinnamamide), o,o-di-n-octadecyl-3-5-di-tert-butyl-4-hydroxybenzyl phosphonate, octadecyl 3-(3′

,5′

-di-tert-butyl-4′

-hydroxyphenyl) proprionate, thiodiethylene bis-(3,5-di-tert-butyl-4-hydroxy) hydrocinnamate, octylated diphenylamine, 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene, 2,6-di-tert-butyl-4-n-butylphenol, 4,4′

methylenebis (2,6-di-tert-butylphenol), 2,6-di-tert-butyl-α

-dimethylamino-p-cresol, 2,6-di-tert-butyl-4-ethylphenol, or combinations of the above.

21. The method of claim 16, wherein the semi-permeable membrane comprises from about 0.01 wt % to about 3 wt % of the antioxidant, based on the total dry weight of the semi-permeable membrane.

22. The method of claim 21, wherein the semi-permeable membrane comprises from about 0.01 wt % to about 1 wt % of the antioxidant, based on the total dry weight of the semi-permeable membrane.