Non-polymeric lipophilic pharmaceutical implant compositions for intraocular use

• US 7,678,827 B2
• Filed: 06/30/2003
• Issued: 03/16/2010
• Est. Priority Date: 07/15/2002
• Status: Expired due to Fees

• Current Assignee: Novartis Ag
• Original Assignee: Alcon Incorporated
• Inventors: Kabra, Bhagwati P., Howie, Janet D.
• Primary Examiner(s): Silverman; Eric E.
• Application Number:
  US10/610,435
• Publication Number:
  US 20040013704A1
• Time in Patent Office: 2,451 Days
• Field of Search: None
• US Class Current: 514/424
• 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
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents

Abstract

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

Claims

1. An implant composition comprising a blend mixture of a lipophilic compound having a molecular weight of 150-4000 and a pharmaceutically effective amount of a drug, wherein the implant composition contains neither a polymeric ingredient nor an organic solvent that is miscible with or dispersible in water, wherein the implant composition is solid at a temperature of 37°

C. and becomes a liquid above 37°

C., and said implant composition is solidifiable in a human, and the lipophilic compound is of the formula

2. The implant composition of claim 1 wherein the molecular weight of the lipophilic compound of formula (I) is ≦

2000.

3. The implant composition of claim 2 wherein the molecular weight of the lipophilic compound of formula (I) is ≦

1000.

4. The implant composition of claim 1 wherein the composition comprises a mixture of two or more lipophilic compounds of formula (I).

5. The implant composition of claim 1 wherein the lipophilic compound of formula (I) has a melting point ≧

37°

C.

6. The implant composition of claim 4 wherein at least one lipophilic compound of formula (I) has a melting point <

37°

C. but the mixture of two or more lipophilic compounds of formula (I) has a melting point ≧

37°

C.

7. The implant composition of claim 1, wherein said implant composition is an intraocular implant composition and said implant composition is solidifiable in an eye of said human.

8. The implant composition of claim 1 wherein R¹ is, —

C_nH_2n+1-2m, —

COOC_nH_2n+1-2m, —

COO(CH₂CH₂O)_nCH₂CH₂OH, —

CH₂R³, or

9. The implant composition of claim 8 wherein R¹ is

10. The implant composition of claim 1 wherein the composition comprises at least 50% (wt.) of the lipophilic compound of formula (I).

11. The implant composition of claim 1 wherein the drug is selected from the group consisting of anti-glaucoma agents;

anti-infective agents;

non-steroidal and steroidal anti-inflammatory agents;

growth factors;

immunosuppressant agents;

neuroprotectant agents;

angiogenesis-inhibiting agents and anti-allergy agents.

12. The implant composition of claim 1 wherein the composition further comprises one or more excipients selected from the group consisting of surfactants, preservatives, and stabilizers.

13. The implant composition of claim 12 wherein the composition comprises a surfactant selected from the group consisting of tyloxapol;

polysorbate 20;

polysorbate 60; and

polysorbate 80.

14. The implant composition of claim 12 wherein the composition comprises a preservative selected from the group consisting of quaternary ammonium preservatives.

15. The implant composition of claim 12 wherein the composition comprises a stabilizer selected from the group consisting of chelating agents;

and antioxidants.

16. The implant composition of claim 1 wherein the composition has a cylindrical, conical or spherical shape.

17. A method of delivering an ophthalmically acceptable drug to the eye comprising the steps of

(a) preparing the implant composition of claim 1 and

(b) implanting the composition prepared in step (a) in the eye.

18. The method of claim 17 wherein in step (b) the composition prepared in step (a) is implanted in a site selected from the group consisting of the conjunctival cul-de-sac;

punctum;

lacrimal canaliculus;

anterior segment;

posterior segment;

sub-Tenon'"'"'s space;

suprachoroidal space; and

subconjunctival space.

19. The method of claim 17 wherein the composition is warmed to a temperature above room temperature and administered through a cannula.

20. The method of claim 17 wherein the composition is administered as a solid or semi-solid.

21. The method of claim 17 wherein the intraocular implant composition of step (a) is suspended in a liquid carrier and implanted in the eye in step (b) by administration through a cannula.

22. An intraocular implant composition comprising a blend mixture of a lipophilic compound having a molecular weight of 150-4000 and a pharmaceutically effective amount of a drug, wherein the implant composition contains neither a polymeric ingredient nor an organic solvent that is miscible with or dispersible in water, wherein the composition is solid at a temperature of 37°

C. and becomes a liquid above 37°

C., and said composition is solidifiable in a human eye, and the lipophilic compound is of the formula

23. An intraocular implant composition comprising a blend mixture of a lipophilic compound having a molecular weight of 150-4000 and a pharmaceutically effective amount of a drug, wherein the implant composition contains neither a polymeric ingredient nor an organic solvent that is miscible with or dispersible in water, wherein the composition is solid at a temperature of 37°

C. and becomes a liquid above 37°

C., and said composition is solidifiable in a human eye, and the lipophilic compound is of the formula