Ophthalmic Pharmaceutical Compositions and Methods of Making and Using Same

• US 20130210912A1
• Filed: 01/11/2013
• Published: 08/15/2013
• Est. Priority Date: 02/13/2012
• Status: Active Grant

• Current Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Inventors: Davio, Stephen R., Sarkar, Paramita, Marlowe, Zora T., Glass, Brian J., Kleiber, Tammy J.
• Granted Patent: US 9,278,132 B2
• Time in Patent Office: Days
• US Class Current: 514/530
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A stable ophthalmic pharmaceutical composition for relief, treatment, control, alleviation, or prevention of a pathological ocular condition of the eye comprises: (a) a first polymer, a viscosity of which changes with a change in a concentration of an electrolyte, such as a salt, when added to said first polymer; (b) a second polymer that is different from the first polymer and can modify the viscosity of the first polymer; and (c) an oil. In some embodiments, the composition further comprises a non-ionic surfactant. The composition can form a stable oil-in-water emulsion on storage, but separate into an oil phase and a water phase when applied in the eye. The emulsion can comprises an ophthalmic active pharmaceutical ingredient dissolved in the oil or water phase. The emulsion can provide enhanced stability to said active pharmaceutical ingredient.

Claims

1. An ophthalmic pharmaceutical composition comprising:

(a) a first polymer, a viscosity of which changes with a change in a concentration of an electrolyte, when added to said first polymer or a composition comprising said first polymer;

(b) a second polymer that is different from the first polymer and can modify a viscosity of said first polymer; and

(c) an oil.

2. The composition of claim 1, further comprising (d) water.

3. The composition of claim 2, further comprising (e) a non-ionic surfactant.

4. The composition of claim 2;

wherein said oil comprises a medium-chain triglyceride.

5. The composition of claim 4, wherein said first polymer comprises a polymer or copolymer of carboxyvinyl monomers, and said second polymer comprises a polyanionic polysaccharide.

6. The composition of claim 5, wherein said composition comprises an oil phase-in-water phase emulsion.

7. The composition of claim 6, wherein said emulsion is stable on storage but separates into water phase and oil phase when diluted with tear resident in the eye.

8. The composition of claim 7, wherein said polyanionic polysaccharide is selected from the group consisting of alginate, hyaluronic acid, glucuronoxylomannan, carboxymethylcellulose, carboxyethylcellulose, glucosaminoglycan, pectin, and xanthan gum.

9. The composition of claim 8, wherein said first polymer is present at a concentration of 0.01-2 percent by weight of the total composition, and said polyanionic polysaccharide is present at a concentration of 0.01-2 percent by weight of the total composition.

10. The composition of claim 9, wherein said composition has a viscosity in the range from about 5 to about 2000 centipoises.

11. The composition of claim 1, further comprising an active pharmaceutical ingredient dissolved in said oil.

12. The composition of claim 7, further comprising an active pharmaceutical ingredient dissolved in said oil.

13. The composition of claim 12, wherein said active pharmaceutical ingredient is selected from the group consisting of prostaglandin analogs.

14. The composition of claim 13, wherein said active pharmaceutical ingredient is latanoprost.

15. A method for reducing, ameliorating, treating, or controlling a condition of dry eye, the method comprising:

administering to an affected eye of a patient a composition comprising;

(a) a first polymer, a viscosity of which changes with a change in a concentration of an electrolyte, when added to said first polymer or a composition comprising said first polymer;

(b) a second polymer that is different from the first polymer and can modify the viscosity of said first polymer; and

(c) an oil.

16. The method of claim 15;

wherein the composition further comprises (d) water, and the composition is an oil phase-in-water phase emulsion.

17. The method of claim 16;

wherein the composition is stable on storage but separates into an oil phase and a water phase upon being instilled in the eye.

18. The method of claim 16;

wherein the composition further comprises (e) a non-ionic surfactant.

19. The method of claim 16;

wherein said first polymer comprises a polymer or copolymer of carboxyvinyl monomers, and said second polymer comprises a polyanionic polysaccharide.

20. The method of claim 19, wherein said polyanionic polysaccharide is selected from the group consisting of alginate, hyaluronic acid, glucuronoxylomannan, carboxymethylcellulose, carboxyethylcellulose, glucosaminoglycan, pectin, and xanthan gum.

21. The method of claim 20, wherein said first polymer is present at a concentration of 0.01-2 percent by weight of the total composition, and said polyanionic polysaccharide is present at a concentration of 0.01-2 percent by weight of the total composition.

22. The method of claim 21, wherein said composition further comprises a material selected from the group consisting of tonicity-adjusting agents, buffers, antioxidants, viscosity-adjusting agents, stabilizers, chelating agents, and preservatives.

23. A method for producing a composition, said method comprising combining:

(a) a first polymer, a viscosity of which changes with a change in a concentration of an electrolyte, such as a salt, when added to said first polymer;

(b) a second polymer that is different from the first polymer; and

(c) an oil to produce said composition.

24. The method of claim 23, wherein the method further comprising combining a non-ionic surfactant in said composition.

25. A method for reducing, ameliorating, treating, or controlling ocular hypertension, the method comprising:

administering to an affected eye of a patient a composition comprising;

(a) a first polymer, a viscosity of which changes with a change in a concentration of an electrolyte, when added to said first polymer or a composition comprising said first polymer;

(b) a second polymer that is different from the first polymer and can modify the viscosity of said first polymer;

(c) an oil;

(d) a prostaglandin analog dissolved in said oil; and

(e) water;

wherein said composition is an oil-in-water emulsion.

26. The method of claim 25, wherein said first polymer comprises a cross-linked carboxyvinyl polymer, and said second polymer comprises a polyanionic polysaccharide.

27. The method of claim 26, wherein said prostaglandin analog is latanoprost.

28. The method of claim 27, wherein said oil comprises a medium-chain triglyceride.

29. A method for enhancing a stability of a prostaglandin analog in an ophthalmic pharmaceutical composition, the method comprising:

(a) dissolving said prostaglandin analog in an oil;

(b) adding an aqueous medium to said oil; and

(c) preparing an oil-in-water emulsion from said oil and said aqueous medium;

wherein the method results in a degradation of said prostaglandin analog of less than 5 percent of the original concentration thereof after storage at room temperature for 2 weeks.

30. The method of claim 29, wherein said oil comprises a medium-chain triglyceride, said aqueous medium comprises a cross-linked carboxyvinyl polymer and a polyanionic polysaccharide.