Stabilised prostaglandin composition

• US 8,460,707 B2
• Filed: 03/26/2012
• Issued: 06/11/2013
• Est. Priority Date: 08/05/2004
• Status: Expired due to Fees

• Current Assignee: Ferring BV (Ferring Holding SA)
• Original Assignee: Ferring BV (Ferring Holding SA)
• Inventors: Robertson, Steven
• Primary Examiner(s): DICKINSON, PAUL W
• Application Number:
  US13/429,678
• Publication Number:
  US 20120184615A1
• Time in Patent Office: 442 Days
• Field of Search: None
• US Class Current: 424/486
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 47/30 Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• CPC Class Codes: A61K 9/0031 Rectum, anus
• 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 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/04 for inducing labour or abortion; Uterotonics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A pharmaceutical delivery device, such as a suppository or pessary, comprises a synthetic prostaglandin PGE₁ analogue (e.g. misoprostol) in a solid polyurethane hydrogel. The polyurethane is either linear or cross-linked.

Claims

1. A method for the stabilization of a PGE1 analogue, comprising:

drying a pharmaceutical delivery device comprising a polyurethane hydrogel and a PGE1 analogue disposed in the hydrogel, thereby achieving a water content of the hydrogel in the range of 0.1% to 0.2% by weight.

2. A method according to claim 1, further comprising storing the delivery device at a temperature above 4°

C. after drying.

3. A method according to claim 2, wherein the delivery device is stored at a temperature of about 25°

C.

4. A method according to claim 3 wherein the polyurethane hydrogel is a cross-linked hydrogel.

5. A method according to claim 3, wherein the PGE1 analogue is misoprostol and wherein when the delivery device is stored at 25°

C., the misoprostol potency is 90 to 94% of its initial value after storage for 12 months.

6. A method according to claim 5, wherein the delivery device contains 100 μ

g misoprostol and when the delivery device is stored at 25°

C., the misoprostol potency is at least 94.2% of the initial value after storage for 12 months.

7. A method according to claim 5, wherein the delivery device contains 200 μ

g misoprostol and when the delivery device is stored at 25°

C., the misoprostol potency is at least 93.5% of the initial value after storage for 12 months.

8. A method according to claim 5, wherein the delivery device contains 400 μ

g misoprostol and when the delivery device is stored at 25°

C., the misoprostol potency is at least 90.1% of the initial value after storage for 12 months.

9. A method according to claim 3, wherein the PGE1 analogue is misoprostol, and when the delivery device is stored at 25°

C., the misoprostol potency is greater than 95% of its initial value after storage for 12 months.

10. A method according to claim 9, wherein the delivery device contains 100 μ

g misoprostol and when the delivery device is stored at 25°

C., the misoprostol potency is 97 to 100% of the initial value after storage for 12 months.

11. A method according to claim 9, wherein the delivery device contains 200 μ

g misoprostol and when the delivery device is stored at 25°

C., the misoprostol potency is at least 96.6% of the initial value after storage for 12 months.

12. A method according to claim 9, wherein the delivery device contains 400 μ

g misoprostol and when the delivery device is stored at 25°

C., the misoprostol potency is at least 96.2% of the initial value after storage for 12 months.

13. A method according to claim 4 wherein the cross-linked polyurethane hydrogel is the reaction product of a polyethylene glycol, a triol and a diisocyanate.

14. A method according to claim 13 wherein the triol is hexanetriol.

15. A method according to claim 13 wherein said polyethylene glycol before reaction is selected from the group consisting of PEG2000, PEG4000, PEG6000 or PEG8000.

16. A method according to claim 3 wherein the polyurethane hydrogel is a linear hydrogel.

17. A method according to claim 16 wherein the linear polyurethane hydrogel is the reaction product of a polyethylene oxide, a difunctional compound and a difunctional isocyanate.

18. A method according to claim 17 wherein the polyethylene oxide has a molecular weight ranging between 4000 and 35,000.

19. A method according to claim 17 wherein the polyethylene oxide has an equivalent weight ranging between 4000 and 8000.

20. A method according to claim 17, wherein the difunctional compound is selected from the group consisting of 1,6-hexanediol, 1,10-decanediol, 1,12-dodecanediol or 1,16-hexadecanediol.

21. A method according to claim 20 wherein the delivery device is in the form selected from the group consisting of a suppository, a vaginal pessary, a buccal insert or an implant.

22. A method according to claim 5 wherein said stabilized misoprostol is stable after storage at about 25°

C. for twelve months compared to misoprostol oil.

23. A method according to claim 1, wherein the water content is achieved by packaging the pharmaceutical delivery device with a desiccant.

24. A method according to claim 1, wherein the pharmaceutical delivery device comprises 200 μ

g of the PGE1 analogue.

25. A method according to claim 1, wherein the PGE1 analogue is misoprostol.

26. A method for the stabilization of a PGE1 analogue comprising:

drying a pharmaceutical delivery device comprising a polyurethane hydrogel and a PGE1 analogue disposed in the hydrogel, thereby achieving a water content of the hydrogel of less than 0.1% by weight.

27. A method according to claim 26, wherein the water content is achieved by packaging the pharmaceutical delivery device with a desiccant.

28. A method according to claim 26, wherein the pharmaceutical delivery device comprises 200 μ

g of the PGE1 analogue.

29. A method according to claim 26, further comprising storing the delivery device at a temperature above 4°

C. after drying.

30. A method according to claim 26, wherein the PGE1 analogue is misoprostol.