Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions

• US 5,212,162 A
• Filed: 03/25/1992
• Issued: 05/18/1993
• Est. Priority Date: 03/27/1991
• Status: Expired due to Term

• Current Assignee: Alcon Research Limited (Nestle SA)
• Original Assignee: Alcon Laboratories Incorporated (Alcon Incorporated)
• Inventors: Jani, Rajni, Lang, John C., Missel, Paul J. T.
• Primary Examiner(s): Wityshyn, Michael G.
• Assistant Examiner(s): Leary, Louise N.
• Application Number:
  US07/857,673
• Time in Patent Office: 419 Days
• Field of Search: 514/54, 514/57, 514/912, 514/913, 536/1.1, 424/427
• US Class Current: 514/54
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears

Abstract

Ophthalmic compositions comprising combinations of gelling polysaccharides and finely-divided drug carrier substrates which become relatively more viscous on contact with the eye are disclosed. These ophthalmic compositions are both comfortable and long-lasting Ophthalmic compositions further comprising a pharmaceutically active drug are also disclosed, as are methods of use.

Claims

1. A topical ophthalmic composition comprising a gelling polysaccharide and a finely-divided drug carrier substrate, wherein the concentration of said gelling polysaccharide allows the composition to be administrable as a drop which gels upon instillation to the eye.

2. The composition of claim 1 wherein the finely-divided drug carrier substrate is an ion exchange resin.

3. The composition of claim 1 wherein the gelling polysaccharide concentration is between 0.1% and 3.0% by weight/volume and the concentration of the finely-divided drug carrier substrate is between 0.05% and 10.0% by weight/volume.

4. The composition of claim 1 wherein the gelling polysaccharide is selected from the group consisting of xanthan gum, locust beam gum, gellan gum, and carrageenan.

5. The composition of claim 4 wherein the gelling polysaccharide is gellan gum.

6. The composition of claim 4 wherein the gelling polysaccharide is a carrageenan having not more than 1.0 sulfate moiety per disaccharide repeating unit.

7. The composition of claim 6 wherein said carrageenan is eucheuma carrageenan.

8. The composition of claim 6 wherein said carrageenan is furcellaran.

9. The composition of claim 1 wherein the pre-dosed viscosity thereof is between 1 and 500 cps and the post-dosed viscosity is greater than 50 cps.

10. The composition of claim 1 wherein the pre-dosed viscosity thereof is between 1 and 500 cps and the post-dosed gel has a modulus of elasticity between 1×

10⁴ and 5×

10⁵ dynes/cm².

11. The composition of claim 1 wherein the pre-dosed modulus of elasticity thereof is between 1×

10⁴ and 3×

10⁵ dynes/cm² and the post-dosed modulus of elasticity thereof is between 1×

10⁴ and 2×

10⁶ dynes/cm².

12. The composition of claim 1 wherein the composition is thixotropic, having a pre-dosed modulus of elasticity between 1×

10⁴ and 2×

10⁵ dynes/cm² and, after shaking, a pre-dosed viscosity between 1 and 5000 cps and having a post-dosed modulus of elasticity between 1×

10⁴ and 2×

10⁶ dynes/cm².

13. The composition of claim 1 further comprising an ophthalmic agent.

14. The composition of claim 13 wherein the ophthalmic agent is para-amino clonidine.

15. The composition of claim 13 wherein the ophthalmic agent is a carbonic anhydrase inhibitor.

16. The composition of claim 15 wherein the carbonic anhydrase inhibitor is (+)-4-ethylamino-2,3-dihydro-4H-2-methylthieno-[3,2-e]1,2-thiazine-6-sulfonamide-1,1-dioxide or a pharmaceutically acceptable salt thereof.

17. A method of delivering an ophthalmic agent to the eye which comprises topically administering a composition comprising:

an ophthalmic agent, a gelling polysaccharide, and a finely-divided drug carrier substrate, wherein the concentration of said gelling polysaccharide allows the composition to be administrable as a drop which gels upon instillation to the eye.

18. The method of claim 17 wherein the finely-divided drug carrier substrate is an ion exchange resin.

19. The method of claim 17 wherein the gelling polysaccharide concentration is between 0.1% and 3.0% by weight/volume and the finely-divided drug carrier substrate concentration is between 0.05% and 10.0% by weight/volume.

20. The method of claim 17 wherein the gelling polysaccharide is selected from the group consisting of xanthan gum, locust bean gum, gellan gum, and carrageenan.

21. The method of claim 20 wherein the gelling polysaccharide is gellan gum.

22. The method of claim 20 wherein the gelling polysaccharide is a carrageenan having not more than 1.0 sulfate moiety per disaccharide repeating unit.

23. The method of claim 22 wherein said carrageenan is eucheuma carrageenan.

24. The method of claim 22 wherein said carrageenan is furcellaran.

25. The method of claim 17 wherein the ophthalmic agent is para-amino clonidine.

26. The method of claim 17 wherein the ophthalmic agent is a carbonic anhydrase inhibitor.

27. The method of claim 26 wherein the carbonic anhydrase inhibitor is (+)-4-ethylamino-2,3-dihydro-4H-2-methylthieno-[3,2-e]1,2-thiazine-6-sulfonamide-1,1-dioxide or a pharmaceutically acceptable salt thereof.