Non-Polymeric Lipophilic Pharmaceutical Implant Compositions For Intraocular Use

• US 20080241224A1
• Filed: 06/03/2008
• Published: 10/02/2008
• Est. Priority Date: 07/15/2002
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: Alcon Incorporated
• Inventors: Kabra, Bhagwati P., Howie, Janet D.
• Granted Patent: US 8,178,576 B2
• Time in Patent Office: Days
• US Class Current: 424/428
• 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

1-20. -20. (canceled)

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

(a) preparing an intraocular implant composition comprising a lipophilic compound having a molecular weight of 150-4000 and a pharmaceutically effective amount of a drug, but lacking a polymeric ingredient and an organic solvent that is miscible with or dispersible in water, wherein the composition is solid or semi-solid at temperatures ≦

34°

C. and the lipophilic compound is of the formula

22. The method of claim 21 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.

23. The method of claim 21 wherein the composition is warmed to a temperature above room temperature and administered through a cannula.

24. The method of claim 21 wherein the composition is administered as a solid or semi-solid.

25. The method of claim 21 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.

26. The method of claim 21, wherein the composition is solid or semi-solid at temperatures ≦

34°

C.

27. The method of claim 21, wherein the molecular weight of the lipophilic compound of formula (I) is ≦

2000.

28. The method of claim 21, wherein the molecular weight of the lipophilic compound of formula (I) is ≦

1000.

29. The method of claim 21, wherein the composition comprises a mixture of two or more lipophilic compounds of formula (I).

30. The method of claim 21, wherein the lipophilic compound of formula (I) has a melting point>

37°

C.

31. The method of claim 21, wherein at least one lipophilic compound of formula (I) has a melting point<

37°

C but the mixture has a melting point>

37°

C.

32. The method of claim 21, wherein R¹ is, —

CH<sub>2n+1−

2m</sub>, —

COOC_nH<sub>2n+1−

2m</sub>, —

COO(CH₂CH₂O)_nCH₂CH₂OH, —

CH₂R³, or

33. The method of claim 21, wherein R¹ is

34. The method of claim 21, wherein said lipophilic compound is present in an amount of at least 50 wt % based on the weight of the intraocular implant composition, and wherein the lipophilic compound of formula (I) is diethylene glycol monostearate;

propylene glycol monostearate;

glyceryl monostearate;

glyceryl monolinoleate;

glyceryl monooleate;

or glyceryl monopalmitate;

or any mixture thereof

35. The method of claim 21, wherein said lipophilic compound is present in an amount of at least 50 wt % based on the weight of the intraocular implant composition, and wherein the lipophilic compound of formula (I) is 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;

or glyceryl dibehenate.

36. The method of claim 21, wherein the composition comprises at least 10% (wt.) of the lipophilic compound of formula (I).

37. The method of claim 21, wherein the composition comprises at least 30% (wt.) of the lipophilic compound of formula (I).

38. The method of claim 21, wherein the composition comprises at least 50% (wt.) of the lipophilic compound of formula (I).

39. The method of claim 21, wherein the drug is an anti-glaucoma agent;

anti-infective agent;

non-steroidal and steroidal anti-inflammatory agent;

growth factor;

immunosuppressant agent;

neuroprotectant agent;

angiogenesis-inhibiting agent or anti-allergy agent.

40. The method of claim 21, wherein the composition further comprises one or more excipients selected from the group consisting of surfactants, preservatives, and stabilizers.