Non-Polymeric Lipophilic Pharmaceutical Implant Compositions for Intraocular Use

• US 20070184089A1
• Filed: 04/03/2007
• Published: 08/09/2007
• Est. Priority Date: 07/15/2002
• Status: Abandoned Application

• Current Assignee: Alcon Incorporated
• Original Assignee: Alcon Incorporated
• Inventors: Marsh, David, Kabra, Bhagwati, Slovin, Eliot, Howie, Janet
• Application Number:
  US11/695,990
• Publication Number:
  US 20070184089A1
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• 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 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

Solid or semi-solid intraocular implant compositions are disclosed. The compositions contain a lipophilic compound but lack a polymeric ingredient.

Claims

1. An intraocular implant composition comprising 5 to 15% (w/w) of N-[4-[3-amino-1H-indazol-4-yl]phenyl]-N′

-(2-fluoro-5-methoylphenyl)urea, 0.5 to 5% (w/w) of a surfactant, and 80 to 94.5% (w/w) of a lipophilic compound selected from the group consisting of glyceryl palmitostearate;

diethylene glycol monostearate;

propylene glycol monostearate;

glyceryl monostearate;

glyceryl monolinoleate;

glyceryl monooleate;

glyceryl monopalmitate;

glyceryl monolaurate;

glyceryl dilaurate;

glyceryl monomyristate;

glyceryl dimyristate;

glyceryl monopalmitate;

glyceryl dipalmitate;

glyceryl monostearate;

glyceryl distearate;

glyceryl monooleate;

glyceryl dioleate;

glyceryl monolinoleate;

glyceryl dilinoleate;

glyceryl monoarachidate;

glyceryl diarachidate;

glyceryl monobehenate; and

glyceryl dibehenate; and

mixtures thereof;

provided that the intraocular implant composition does not comprise a polymeric ingredient or an organic solvent that is miscible with or dispersible in water.

2. The intraocular implant composition of claim 1 wherein the lipophilic compound is glyceryl palmitostearate.

3. The intraocular implant composition of claim 1 wherein the surfactant is selected from the group consisting of tyloxapol;

polysorbate 20;

polysorbate 60; and

polysorbate 80.

4. The intraocular implant composition of claim 3 wherein the surfactant is polysorbate 80.

5. The intraocular implant composition of claim 1 wherein the amount of N-[4-[3-amino-1H-indazol-4-yl]phenyl]-N′

-(2-fluoro-5-methoylphenyl)urea is 8 to 12% (W/W).

6. The intraocular implant composition of claim 1 wherein the amount of surfactant is 2.5 to 4.5% (w/w).

7. The intraocular implant composition of claim 1 wherein the amount of lipophilic compound is 80 to 90% (w/w).

8. A method of treating age-related macular degeneration comprising implanting in the eye an intraocular implant composition comprising 5 to 15% (w/w) of N-[4-[3-amino-1H-indazol-4-yl]phenyl]-N′

-(2-fluoro-5-methoylphenyl)-urea, 0.5 to 5% (w/w) of a surfactant, and 80 to 94.5% (w/w) of a lipophilic compound selected from the group consisting of glyceryl palmitostearate;

diethylene glycol monostearate;

propylene glycol monostearate;

glyceryl monostearate;

glyceryl monolinoleate;

glyceryl monooleate;

glyceryl monopalmitate;

glyceryl monolaurate;

glyceryl dilaurate;

glyceryl monomyristate;

glyceryl dimyristate;

glyceryl monopalmitate;

glyceryl dipalmitate;

glyceryl monostearate;

glyceryl distearate;

glyceryl monooleate;

glyceryl dioleate;

glyceryl monolinoleate;

glyceryl dilinoleate;

glyceryl monoarachidate;

glyceryl diarachidate;

glyceryl monobehenate; and

glyceryl dibehenate; and

mixtures thereof;

provided that the intraocular implant composition does not comprise a polymeric ingredient or an organic solvent that is miscible with or dispersible in water.

9. The method of claim 8 wherein the lipophilic compound is glyceryl palmitostearate.

10. The method of claim 8 wherein the surfactant is selected from the group consisting of tyloxapol;

polysorbate 20;

polysorbate 60; and

polysorbate 80.

11. The method of claim 10 wherein the surfactant is polysorbate 80.

12. The method of claim 8 wherein the amount of N-[4-[3-amino-1H-indazol-4-yl]phenyl]-N′

-(2-fluoro-5-methoylphenyl)urea is 8 to 12% (w/w).

13. The method of claim 8 wherein the amount of surfactant is 2.5 to 4.5% (w/w).

14. The method of claim 8 wherein the amount of lipophilic compound is 80 to 90% (w/w).

15. The method of claim 8 wherein the composition is warmed and administered in the eye through a cannula or needle.