Non-polymeric lipophilic pharmaceutical implant compositions for intraocular use

• US 8,178,576 B2
• Filed: 06/03/2008
• Issued: 05/15/2012
• Est. Priority Date: 07/15/2002
• Status: Expired due to Fees

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Kabra, Bhagwati P., Howie, Janet D.
• Primary Examiner(s): VU, JAKE MINH
• Application Number:
  US12/132,003
• Publication Number:
  US 20080241224A1
• Time in Patent Office: 1,442 Days
• Field of Search: 514/424
• 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. 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 a temperature of 37°

C. or less and the lipophilic compound is of the formula

2. The method of claim 1 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.

3. The method of claim 1 wherein the composition is warmed to a temperature above room temperature and administered through a cannula.

4. The method of claim 1 wherein the composition is administered as a solid or semi-solid.

5. The method of claim 1 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.

6. The method of claim 1, wherein the composition is solid or semi-solid at temperatures ≦

34°

C.

7. The method of claim 1, wherein the molecular weight of the lipophilic compound of formula (I) is ≦

2000.

8. The method of claim 1, wherein the molecular weight of the lipophilic compound of formula (I) is ≦

1000.

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

10. The method of claim 1, wherein the lipophilic compound of formula (I) has a melting point >

37°

C.

11. The method of claim 1, wherein at least one lipophilic compound of formula (I) has a melting point <

37°

C. but the composition has a melting point >

37°

C.

12. The method of claim 1, wherein R¹ is, —

C_nH<sub>2n+1−

2m</sub>, —

COOC_nH<sub>2n+1−

2m</sub>, —

COO(CH₂CH₂O)_nCH₂CH₂OH, —

CH₂R³, or

13. The method of claim 1, wherein R¹ is

14. The method of claim 1, 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.

15. The method of claim 1, 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.

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

17. The method of claim 1, wherein the composition comprises at least 30% (wt.) of the lipophilic compound of formula (I).

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

19. The method of claim 1, 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.

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