Water-swellable polymers

• US 8,557,281 B2
• Filed: 07/13/2010
• Issued: 10/15/2013
• Est. Priority Date: 09/27/2002
• Status: Active Grant

• Current Assignee: Ferring BV (Ferring Holding SA)
• Original Assignee: Ferring BV (Ferring Holding SA)
• Inventors: Halliday, Janet A., Tuominen, Jukka, Livingstone, Mark, Koppenhagen, Frank, Currie, Lilias, Stewart, Sarah
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US12/835,436
• Publication Number:
  US 20110091488A1
• Time in Patent Office: 1,190 Days
• Field of Search: 424/468, 514/211.02, 514/11.6
• US Class Current: 424/468
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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: C08G 18/6674 with compounds of group C08G18/3203
• CPC Class Codes: C08G 18/758 containing two or more cycloaliphatic rings
• CPC Class Codes: C08G 2210/00 Compositions for preparing hydrogels

Abstract

A pharmaceutical controlled release composition in solid dosage form is provided which comprises (I) a water-swell able linear polymer obtainable by reacting together: (a) a polyethylene oxide; (b) a C₅ to C₂₀ diol; and (c) a diisocyanate; and (II) a releasable pharmaceutically active agent.

Claims

1. A pharmaceutical controlled release composition in solid dosage form, comprises:

(I) a water-swellable linear polymer obtainable by reacting

(a) a polyethylene oxide;

(b) a C₈ to C₁₅ alkanediol; and

(c) a diisocyanate; and

(II) a releasable pharmaceutically active agent;

wherein the polyethylene oxide has a number average molecular weight of 3000 to 40,000 and the ratio of components (a) to (b) to (c) in terms of equivalent weights is in the range 0.1-1.5 to 1 to 1.1-2.5.

2. A composition according to claim 1 wherein the molecular weight of the active agent is in the range 200 to 20,000.

3. A composition according to claim 1 wherein the active agent is a prostaglandin.

4. A composition according to claim 1 wherein the active agent is terbutaline sulphate, clindamycin sulphate, oxytocin, misoprostol or progesterone.

5. A composition according to claim 1 in the form of a suppository, pessary, buccal insert or film.

6. A composition according to claim 1 wherein the polyethylene oxide has a number average molecular weight of 4000 to 35,000.

7. A composition according to claim 1 wherein the polyethylene oxide has a number average molecular weight of 8000 to 12,000.

8. A composition according to claim 1 wherein the diol is 1,10-decanediol.

9. A composition according to claim 1 wherein the diol is 1,12-dodecanediol.

10. A composition according to claim 1 wherein the ratio of components (a) to (b) to (c) in terms of equivalent weights is in the range 0.2-0.9 to 1 to 1.2-1.9.

11. A composition according to claim 1 wherein the ratio of components (a) to (b) to (c) in terms of equivalent weights is in the range 0.5-0.9 to 1 to 1.5-1.9.

12. A composition according to claim 1 wherein the ratio of components (a) to (b) to (c) in terms of equivalent weights is in the range 0.1-0.9 to 1 to 1.1-1.9.

13. A composition according to claim 1 which is swellable in water up to 500%.

14. A composition according to claim 1 which is swellable in water up to 1700%.

15. A composition according to claim 1 which is soluble in dichloromethane.

16. A composition according to claim 1 wherein the molecular weight of the active agent is up to 200,000.

17. A method of making the composition of claim 1, which comprises reacting together components (a), (b) and (c) to produce the water-swellable linear polymer, and contacting the polymer with the releasable pharmaceutically active agent.

18. The method of claim 17, wherein the contacting step comprises contacting the polymer with an aqueous solution containing the pharmaceutically active agent to form a hydrogel.

19. The method of claim 18, further comprising drying the hydrogel to form the pharmaceutical controlled release composition.

21. The composition of claim 18, wherein the water-swellable linear polymer has a water swelling percentage of 250% to 1700%.

22. The composition of claim 18, wherein the water-swellable linear polymer has a water swelling percentage of 300% to 1700%.

20. A pharmaceutical controlled release composition in solid dosage form, comprising:

(I) a water-swellable linear polymer obtained by reacting

(a) a polyethylene oxide;

(b) a C₅ to C₂₀ alkanediol; and

(c) a diisocyanate; and

(II) a releasable pharmaceutically active agent;

wherein the water-swellable linear polymer has a water swelling percentage of 250% to 2000%, wherein the polyethylene oxide has a number average molecular weight of 3000 to 40,000, and the ratio of components (a) to (b) to (c) in terms of equivalent weights is in the range 0.1-1.5 to 1 to 1.1-2.5.

23. A pharmaceutical controlled release composition in solid dosage form, consisting of:

(I) a water-swellable linear polymer obtained by reacting

(a) a polyethylene oxide;

(b) a C₅ to C₂₀ alkanediol; and

(c) a diisocyanate; and

(II) a releasable pharmaceutically active agent;

wherein the water-swellable linear polymer is a random copolymer and the dosage form is a pessary or suppository, wherein the polyethylene oxide has a number average molecular weight of 3000 to 40,000, and the ratio of components (a) to (b) to (c) in terms of equivalent weights is in the range 0.1-1.5 to 1 to 1.1-2.5.