DUAL ADHESIVE TECHNOLOGY

• US 20090324714A1
• Filed: 06/26/2009
• Published: 12/31/2009
• Est. Priority Date: 06/27/2008
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: LIU, Xiuying, KRESEVIC, John
• Application Number:
  US12/492,480
• Publication Number:
  US 20090324714A1
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/2853 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A dual adhesive layer dosage form for delivery of active agent to and across, the mucosa is disclosed. Particularly, bioadhesive tablets for administration at the vaginal mucosa are disclosed as having a central active layer sandwiched between two bioadhesive layers.

Claims

1. A pharmaceutical dosage form comprising:

an active layer comprising a pharmaceutically effective amount of an active agent in a swellable hydrophilic matrix;

at least two bioadhesive layers, comprising a bioadhesive agent;

wherein said active layer is disposed between said at least two bioadhesive layers.

2. The pharmaceutical dosage form of claim 1, wherein

said hydrophilic matrix is selected from hydroxypropyl methyl cellulose (HPMC), polyethylene oxide, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methylcellulose (MC), polyvinylpyrrolidone (PVP), xanthan gum, and guar gum, or combinations thereof.

3. The pharmaceutical dosage form of claim 2, wherein said hydrophilic matrix comprises about 10% to about 55% of said active layer by weight.

4. The pharmaceutical dosage form of claim 1, wherein

said bioadhesive agent is selected from polyacrylic acid derivatives, cellulose derivatives, substances of natural origin, protein, mucilaginous substances from edible vegetables, and combinations thereof.

5. The pharmaceutical dosage form of claim 4, where said bioadhesive agent comprises about 10% to about 30% of said bioadhesive layers by weight.

6. The pharmaceutical dosage form of claim 4, wherein

said bioadhesive agent is a polyacrylic acid derivative selected from polycarbophil, high molecular weight cross-linked acrylic acid polymers, polyamides, polycarbonates, polyalkylenes, polyalkyleneglycols, polyalkyleneoxides, polyalkyleneterephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyglycolides, polysiloxanes, polyurethanes, and combinations thereof.

7. The pharmaceutical dosage form of claim 6, wherein said bioadhesive agent is a Carbomer Homopolymer Type B USP/NF.

8. The pharmaceutical dosage form of claim 1, wherein said active agent is selected from:

analgesics and/or anesthetics, anti-infective agents, spermicides, hormones, estrogens, estrogen receptor modulators, progestin, biological or biotherapuetic active agents, absorption or permeation enhancers, deodorizers and combinations thereof.

9. The pharmaceutical dosage form of claim 8, wherein said Analgesic and/or anesthetic is selected from non-steroidal anti-inflammatory drugs (NSAIDS), COX-2 inhibitors, opiates and morphinomimetics, lidocaine, prilocaine, and combinations thereof.

10. The pharmaceutical dosage form of claim 9, wherein said active agent is selected from aspirin, ibuprofen, acetaminophen and combinations thereof.

11. The pharmaceutical dosage form of claim 8, wherein said anti-infective agent is selected from antibiotics, sulfonamides, antivirals, antifungals, antiprotozoan, and combinations thereof.

12. The pharmaceutical dosage form of claim 8, wherein said spermicide is selected from nonoxynol-9, octoxynol-9, benzalkonium chloride, ricinoleic acid, phenol mercuric acetates and combinations thereof.

13. The pharmaceutical dosage form of claim 8, wherein said estrogens are selected from conjugated estrogens (CE), synthetic conjugated estrogens, esterified estrogens, 17β

-estradiol, estradiol acetate, estropipate, estradiol hemihydrate and combinations thereof.

14. The pharmaceutical dosage form of claim 8, wherein said estrogens are conjugated estrogens (CE) or synthetic conjugated estrogens.

15. The pharmaceutical dosage form of claim 8, wherein said progestin is selected from medroxyprogesterone acetate, norethindrone, norgestel, megestrol acetate, progesterone, levonorgestrel, drospirenone, norgestimate, methyltestosterone and combinations thereof.

16. The pharmaceutical dosage form of claim 1, wherein said bioadhesive layers are joined so as to substantially envelop the active layer.

30. The pharmaceutical dosage form of claim 1, wherein the active agent is a biological or biotherapeutical active agent.

31. The pharmaceutical dosage form of claim 1, further comprising:

an outer coating which dissolves at greater than about pH 4.

32. The pharmaceutical dosage form of claim 31, wherein said outer coating is selected to facilitate dissolution of the outer coating in the small intestine.

33. The pharmaceutical dosage form of claim 31, further comprising an outer coating which dissolves at greater than about pH 5.

34. The pharmaceutical dosage form of claim 33, wherein said outer coating is selected to facilitate dissolution of the outer coating in the lower bowel or colon.

35. The pharmaceutical dosage form of claim 1, wherein said active layer further comprises one or more controlled release agents.

36. The pharmaceutical dosage form of claim 1, wherein said active layer further comprises one or more absorption or permeation enhancer.

37. The pharmaceutical composition of claim 1, wherein at least one of said active layer and said bioadhesive layers further comprises one or more absorption/permeation enhancer.

17. A pharmaceutical dosage form comprising:

an active layer comprising an effective amount of an active agent in a swellable hydrophilic matrix, wherein;

said hydrophilic matrix is selected from hydroxypropyl methyl cellulose (HPMC), polyethylene oxide, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methylcellulose (MC), polyvinylpyrrolidone (PVP), xanthan gum, and guar gum, and combinations thereof;

said active agent is selected from analgesics and/or anesthetics, anti-infective agents, spermicides, estrogens, progestin, deodorizers, and combinations thereof

at least two bioadhesive layers, comprising a bioadhesive agent selected from polyacrylic acid derivatives, cellulose derivatives, substances of natural origin, protein, mucilaginous substances from edible vegetables, and combinations thereof;

wherein said active layer is disposed between said at least two bioadhesive layers.

18. The pharmaceutical dosage form of claim 17, wherein

said bioadhesive agent is a polyacrylic acid derivative selected from polycarbophil, high molecular weight cross-linked acrylic acid polymers, polyamides, polycarbonates, polyalkylenes, polyalkyleneglycols, polyalkyleneoxides, polyalkyleneterephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyglycolides, polysiloxanes, polyurethanes, and combinations thereof.

19. The pharmaceutical dosage form of claim 18, wherein said bioadhesive agent is a Carbomer Homopolymer Type B USP/NF.

20. The pharmaceutical dosage form of claim 17, wherein said Analgesic and/or anesthetic is selected from non-steroidal anti-inflammatory drugs (NSAIDS), COX-2 inhibitors, opiates and morphinomimetics, lidocaine, prilocaine, or other analgesics and anesthetics known in the pharmaceutical arts, as well as combinations thereof.

21. The pharmaceutical dosage form of claim 20, wherein said active agent is selected from aspirin, ibuprofen, acetaminophen and combinations thereof.

22. The pharmaceutical dosage form of claim 17, wherein said Anti-infective agent is selected from antibiotics, sulfonamides, antivirals, antifungals, antiprotozoan, and combinations thereof.

23. The pharmaceutical dosage form of claim 17, wherein said spermicide is selected from nonoxynol-9, octoxynol-9, benzalkonium chloride, ricinoleic acid, phenol mercuric acetates and combinations thereof.

24. The pharmaceutical dosage form of claim 17, wherein said Estrogens are selected from conjugated estrogens (CE), synthetic conjugated estrogens, esterified estrogens, 17β

-estradiol, estradiol acetate, estropipate, estradiol hemihydrate and combinations thereof.

25. The pharmaceutical dosage form of claim 17, wherein said estrogens are conjugated estrogens (CE) or synthetic conjugated estrogens.

26. The pharmaceutical dosage form of claim 17, wherein said Progestin is selected from medroxyprogesterone acetate, norethindrone, norgestel, megestrol acetate, progesterone, levonorgestrel, drospirenone, norgestimate, methyltestosterone and combinations thereof.

27. The pharmaceutical dosage form of claim 17, wherein said bioadhesive layers are joined so as to substantially envelop the active layer.

29. The tablet of claim 27, wherein

said active layer comprises

about 8-10% conjugated estrogens of said active layer by weight;

about 10% to about 55% hydroxypropylmethyl cellulose of said active layer by weight; and

said bioadhesive layers comprises

about 20% Carbomer Homopolymer Type B USP/NF by weight of the bioadhesive layers.

28. A tablet comprising

an active layer comprising an effective amount of conjugated estrogens in a swellable hydroxypropylmethyl cellulose hydrophilic matrix;

two bioadhesive layers comprising Carbomer Homopolymer Type B USP/NF;

wherein said active layer is sandwiched between said two bioadhesive layers.