Ophthalmic pharmaceutical compositions and methods of making and using same

• US 9,278,132 B2
• Filed: 01/11/2013
• Issued: 03/08/2016
• 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.
• Primary Examiner(s): FAY, ZOHREH A
• Application Number:
  US13/739,018
• Publication Number:
  US 20130210912A1
• Time in Patent Office: 1,152 Days
• US Class Current: 1/1
• 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 an oil-in-water emulsion that comprises:

(a) a first polymer comprising a polymer or copolymer of carboxyvinyl monomers;

the first polymer being present at a concentration in the range from about 0.01 to about 1 percent by weight of the composition;

(b) a second polymer comprising a polyanionic polysaccharide selected from the group consisting of alginic acid, hyaluronic acid, salts of alginic acid or hyaluronic acid, and glucuronoxylomannan extracted from Tremella fuciformis mushroom;

the second polymer being present at a concentration in the range from about 0.01 to about 1 percent by weight of the composition;

(c) a caprylic acid/capric acid medium-chain triglyceride present at a concentration in the range from about 0.01 to about 1 percent by weight of the composition;

(d) a non-ionic surfactant present at a concentration in the range from about 0.01 to about 1 percent by weight of the composition; and

(e) water;

wherein the emulsion is stable on storage but breaks up into separate aqueous and oil phases when diluted with simulated tear or subjected to shear stress; and

wherein the composition has a viscosity in the range from about 2 to about 1000 cP.

2. The composition of claim 1, wherein said composition has a viscosity in the range from about 100 to about 1000 centipoises.

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

4. The composition of claim 2, further comprising an active pharmaceutical ingredient dissolved in said oil.

5. The composition of claim 4, wherein said active pharmaceutical ingredient is selected from the group consisting of prostaglandin analogs.

6. The composition of claim 5, wherein said active pharmaceutical ingredient is latanoprost.

7. A pharmaceutical composition consisting essentially of:

(a) a carboxyvinyl polymer at a concentration from about 0.1 to about 0.5 percent by weight of the total composition;

(b) a polysaccharide that is selected from the group consisting of alginic acid, hyaluronic acid, salts of alginic acid or hyaluronic acid, and glucuronoxylomannan extracted from Tremella fuciformis mushroom and that is present in the composition at a concentration from about 0.05 to about 0.5 percent by weight of the total composition;

(c) a caprylic acid/capric acid medium-chain triglyceride at a concentration from about 0.2 to about 0.5 percent by weight of the total composition;

(d) a single non-ionic surfactant selected from the group consisting of Octoxynol 40, polysorbate 80, and Cremopor EL, at a concentration from about 0.01 to about 0.5 percent by weight of the total composition;

(e) a polyol selected from the group consisting of glycerin, propylene glycol, and mixture thereof, at a concentration from about 0.1 to about 1 percent by weight of the total composition; and

(f) water;

wherein the composition is a stable oil-in-water emulsion in storage but breaks up into separate aqueous phase and oil phase when diluted with simulated tear.

8. A pharmaceutical composition consisting essentially of:

(a) a carboxyvinyl polymer at a concentration from about 0.1 to about 0.5 percent by weight of the total composition;

(b) a polysaccharide that is selected from the group consisting of alginic acid, hyaluronic acid, salts thereof, and glucuronoxylomannan extracted from Tremella fuciformis mushroom and that is present in the composition at a concentration from about 0.05 to about 0.5 percent by weight of the total composition;

(c) a caprylic/capric acid medium-chain triglyceride at a concentration from about 0.2 to about 0.5 percent by weight of the total composition;

(d) a single non-ionic surfactant selected from the group consisting of Octoxynol 40, polysorbate 80, and Cremopor EL, at a concentration from about 0.01 to about 0.5 percent by weight of the total composition;

(e) a polyol selected from the group consisting of glycerin, propylene glycol, and mixture thereof, at a concentration from about 0.1 to about 1 percent by weight of the total composition; and

(f) boric acid and borate buffer;

wherein the composition has a pH from about 7 to about 7.5; and

wherein the composition is a stable oil-in-water emulsion in storage but breaks up into separate aqueous phase and oil phase when diluted with simulated tear.