Stabilised prostaglandin composition

• US 8,491,934 B2
• Filed: 07/28/2005
• Issued: 07/23/2013
• 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:
  US11/573,256
• Publication Number:
  US 20070212391A1
• Time in Patent Office: 2,917 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 pharmaceutical delivery device comprising a formulation comprising stabilized misoprostol in a polyurethane hydrogel, wherein the hydrogel has a water content of less than 0.1% by weight, and wherein said stabilized misoprostol is stable after storage at 25°

C. for twelve months compared to misoprostol oil.

3. A delivery device according to claim 1 or 2 wherein the polyurethane hydrogel is a cross-linked hydrogel.

4. A delivery device according to claim 3 wherein the cross-linked polyurethane is the reaction product of a polyethylene glycol, a triol and a diisocyanate.

5. A delivery device according to claim 4 wherein the polyethylene glycol before reaction is selected from the group consisting of PEG2000, PEG4000, PEG6000 or PEG8000.

6. A delivery device according to claim 5 wherein the polyethylene glycol has a molecular weight ranging between 4000 and 35,000.

7. A delivery device according to claim 6 wherein the polyethylene glycol has a molecular weight ranging between 4000 and 8000.

8. A delivery device according to claim 5 wherein the polyurethane hydrogel is a linear hydrogel.

9. A delivery device according to claim 4 wherein the triol is hexanetriol.

10. A delivery device according to claim 3 wherein the misoprostol is present in an amount ranging between 25 and 400 μ

g.

11. A delivery device according to claim 3 wherein the misoprostol is present in an amount of 100 μ

g.

12. A delivery device according to claim 3 further comprising butylated hydroxyl anisole.

13. A delivery device according to claim 4 wherein the diisocyanate is selected from the group consisting of dicyclohexylmethane diisocyanate, dicyclohexylmethane-4,4-diisocyanate, diphenylmethane-4, 4-diisocyanate, or 1,6-hexamethylene diisocyanate.

14. A delivery device according to claim 3 selected from the group consisting of a suppository, a vaginal pessary, a buccal insert or an implant.

15. A method for inducing labor comprising contacting the delivery device of claim 3 with a body cavity.

16. The method according to claim 15 wherein the delivery device is a vaginal pessary.

20. A delivery device according to claim 3, 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.

21. A delivery device according to claim 20, 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.

22. A delivery device according to claim 20, 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.

23. A delivery device according to claim 20, 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.

24. A delivery device according to claim 3, wherein the water content is 0.1 to 0.2% by weight, 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.

25. A delivery device according to claim 23, 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.

26. A delivery device according to claim 24, 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.

27. A delivery device according to claim 24, 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.

28. A delivery device according to claim 1, wherein the misoprostol is present in an amount of 200 μ

g.

30. An article, comprising:

a pharmaceutical delivery device according to claim 1, and

a desiccant.

2. A pharmaceutical delivery device comprising a formulation comprising stabilized misoprostol in a polyurethane hydrogel, wherein the hydrogel has a water content in the range of 0.1% to 0.2% by weight and wherein said stabilized misoprostol is stable after storage at 25°

C. for twelve months compared to misoprostol oil.

29. A delivery device according to claim 2, wherein the misoprostol is present in an amount of 200 μ

g.

31. An article, comprising:

a pharmaceutical delivery device according to claim 2, and

a desiccant.

17. A pharmaceutical formulation comprising a desiccated polyurethane hydrogel loaded with a predetermined amount of stabilized misoprostol wherein the water content of said hydrogel is 0.1% to 0.2% by weight and wherein said stabilized misoprostol is stable after storage at 25°

C. for twelve months compared to misoprostol oil.

18. A pharmaceutical formulation according to claim 17 wherein the predetermined amount of stabilized misoprostol is between 100 micrograms and 400 micrograms.

19. A pharmaceutical formulation according to claim 17 wherein said hydrogel is crosslinked.