Ophthalmic suspension composition

Patent metadata

Field	Value
Publication number	US-12589069-B2
Application number	US-202218086286-A
Country	US
Kind code	B2
Filing date	Dec 21, 2022
Priority date	Jan 26, 2015
Publication date	Mar 31, 2026
Grant date	Mar 31, 2026

Abstract

A suspension includes an ophthalmic active ingredient suspended in a formulation vehicle including a suspending agent and a non-ionic cellulose derivative. The ophthalmic active agent is present as particles having Dv90<5 μm and Dv50<1 μm. The suspension may be administered to a patient for treating an ophthalmic inflammatory condition.

First claim

What is claimed is:

1 . An ophthalmic suspension comprising an ophthalmic active ingredient suspended in a formulation vehicle, wherein the ophthalmic active ingredient is present as milled particles that have D v50 <1 μm, and the formulation vehicle comprises a suspending agent comprising a carboxyvinyl polymer and a particle size stabilizing agent comprising a non-ionic cellulose derivative, wherein the non-ionic cellulose derivative is hydroxypropylmethyl cellulose, the carboxyvinyl polymer is polycarbophil, the ophthalmic active ingredient is loteprednol etabonate, and the suspension comprises loteprednol etabonate at about 0.38 wt %, polycarbophil at 0.1-0.5 wt %, and hydroxypropylmethyl cellulose at 0.1-0.5 wt %.

2 . The suspension of claim 1 , which is storage stable for at least one year.

3 . The suspension of claim 1 , which is storage stable for at least two years.

4 . The suspension of claim 1 , wherein the loteprednol etabonate is present as particles that have D v90 <5 μm.

5 . The suspension of claim 1 , wherein the non-ionic cellulose derivative is hydroxypropylmethyl cellulose E3LV and is present at a concentration of at least 0.25%.

6 . The suspension of claim 1 , wherein the non-ionic cellulose derivative is hydroxypropylmethyl cellulose E4M.

7 . The suspension of claim 1 , wherein the poloxamer nonionic surfactant comprises poloxamer 407.

8 . The suspension of claim 1 , comprising hydroxypropylmethyl cellulose E3LV or hydroxypropylmethyl cellulose E4M, present at 0.15-0.25 wt %.

9 . The suspension of claim 1 , comprising hydroxypropylmethyl cellulose E4M at 0.15-0.25 wt %.

10 . The suspension of claim 1 , wherein the loteprednol etabonate is present as particles having D v90 <3 μm.

11 . The suspension of claim 1 , wherein the loteprednol etabonate is present as particles having D v90 <3 μm and D v50 <0.6 μm.

12 . The ophthalmic suspension of claim 1 , wherein upon storage of the suspension at 40° C. for 8.5 months, the particles will subsequently have a volume mean diameter of less than or equal to 1.23 micrometers measured using light diffraction.

13 . The ophthalmic suspension of claim 1 , wherein the suspension further comprises benzalkonium chloride at 0.001-0.01 wt %, edetate disodium dihydrate at 0.01-0.1 wt %, sodium chloride at 0.01-0.1 wt %, poloxamer nonionic surfactant at 0.1-1.0 wt %, and glycerin and propylene glycol at 0.1-2 wt %.

14 . The ophthalmic suspension of claim 13 , wherein the suspension further comprises a borate buffer at 0.01-1 wt %.

15 . A method of treating an ophthalmic inflammatory condition comprising administering to an eye of a patient in need of said treating a suspension comprising an ophthalmic anti-inflammatory active ingredient suspended in a formulation vehicle, wherein the ophthalmic anti-inflammatory active ingredient is present as milled particles that have D v50 <1 μm, and the formulation vehicle comprises a suspending agent comprising a carboxyvinyl polymer and a particle size stabilizing agent comprising a non-ionic cellulose derivative, wherein the non-ionic cellulose derivative is hydroxypropylmethyl cellulose, the carboxyvinyl polymer is polycarbophil, the ophthalmic active ingredient is loteprednol etabonate, and the suspension comprises loteprednol etabonate at about 0.38 wt %, polycarbophil at 0.1-0.5 wt %, and hydroxypropylmethyl cellulose at 0.1-0.5 wt %.

16 . The method of claim 15 , wherein the loteprednol etabonate is present as particles that have D v90 <5 μm and D v50 <1 μm.

17 . The method of claim 15 , wherein the suspension further comprises benzalkonium chloride at 0.001-0.01 wt %, edetate disodium dihydrate at 0.01-0.1 wt %, sodium chloride at 0.01-0.1 wt %, poloxamer nonionic surfactant at 0.1-1.0 wt %, and glycerin and propylene glycol at 0.1-2 wt %.

18 . The method of claim 17 , wherein the suspension further comprises a borate buffer at 0.01-1 wt %.

19 . The method of claim 15 , wherein the suspension comprises hydroxypropylmethyl cellulose E3LV or hydroxypropylmethyl cellulose E4M, present at 0.15-0.25 wt %.

20 . The method of claim 15 , wherein the suspension comprises hydroxypropylmethyl cellulose E4M at 0.15-0.25 wt %.

Assignees

• Bausch & Lomb Ireland Ltd

Inventors

• Shawer Mohannad
• Phillips Eric
• Coffey Martin J

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61K9/146

  with organic macromolecular compounds · CPC title

• A61K47/06

  Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title