Low temperature processes for making cyclic lipid implants for intraocular use

• US 20080145403A1
• Filed: 12/19/2006
• Published: 06/19/2008
• Est. Priority Date: 12/19/2006
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Luu, Michelle, Spada, Lon T., Chang, James N.
• Granted Patent: US 8,846,073 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/10 for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 27/12 for cataracts
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals

Abstract

Biocompatible implants comprising a cyclic lipid therapeutic agent are made using a low temperature melt extrusion process. The implants are suitable for intraocular use to treat an ocular condition.

Claims

1. A low temperature process for making an intraocular implant, the process comprising the steps of:

(a) combining a cyclic lipid therapeutic agent and a polymer to form a mixture;

(b) heating the mixture to a temperature between about 50°

C. and about 80°

C., and;

(c) extruding the heated mixture, thereby making an implant suitable for intraocular use.

2. The process of claim 1, wherein the cyclic lipid therapeutic agent is selected from the group consisting of prostaglandins, prostaglandin analogs, and mixtures thereof.

3. The process of claim 1 wherein the cyclic lipid therapeutic agent is selected from the group consisting of bimatoprost, bimatoprost analogs, latanoprost, latanoprost analogs, travoprost, travoprost analogs, unoprostone, unoprostone analogs, prostaglandin E1 and prostaglandin E1 analogs, prostaglandin E2 and prostaglandin E2 analogs, and mixtures thereof.

4. The process of claim 3 wherein the cyclic lipid therapeutic agent is selected from the group consisting of bimatoprost, bimatoprost analogs, and mixtures thereof.

5. The process of claim 1 wherein the polymer is a biodegradable polymer.

6. The process of claim 5 wherein the biodegradable polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polylactide-co-glycolide, and copolymers thereof.

7. The process of claim 1 wherein the polymer comprises from about 30% to about 95% by weight of the implant.

8. The process of claim 1 wherein the cyclic lipid therapeutic agent comprises from about 5% to about 70% by weight of the implant.

9. The process of claim 1, wherein a potency of the cyclic lipid therapeutic agent released from the implant is at least about 50% of its maximum potency.

11. The implant made by the process of claim 1.

23. A method for treating an ocular condition, the method comprising the step of intraocular administration of the implant made by the process of claim 1.

24. The method of claim 23, wherein the intraocular administration is selected from a location selected from the group consisting of the anterior chamber, the posterior chamber, the vitreous cavity, the choroid, the suprachoroidal space, the subretinal space, the conjunctiva, the subconjunctival space, the episcleral space, the intracorneal space, the epicorneal space, the sclera, the pars plana, surgically-induced avascular regions, the macula, the retina and sub-tenon locations.

10. A low temperature process for making an intraocular implant, the process comprising the steps of:

(a) combining a prostaglandin analog and a biodegradable polymer to form a mixture;

(b) heating the mixture to a temperature between about 50°

C. and about 80°

C., and;

(c) extruding the heated mixture, thereby making an implant suitable for intraocular use.

12. A process for making an intraocular implant, the process comprising the steps of:

(a) combining;

(i) a cyclic lipid therapeutic agent;

(ii) a first biodegradable polymer, and;

(ii) a second biodegradable polymer to form a mixture, wherein;

(α

) the first biodegradable polymer and the second biodegradable polymer are different polymers;

(β

) the solubilities of the cyclic lipid therapeutic agent, the first biodegradable polymer, and the second biodegradable polymer are substantially similar, and;

(γ

) the melt temperature of the second biodegradable polymer is lower than the melt transition temperature of the first biodegradable polymer,

(b) heating the mixture to the lower melt temperature of the second biodegradable polymer, so that the second biodegradable polymer can function as a solvent for the cyclic lipid therapeutic agent and for the first biodegradable polymer, wherein the melt temperature of the second biodegradable polymer is lower than the temperature at which the cyclic lipid therapeutic agent exhibits a substantial loss of potency, and;

(c) extruding the heated mixture, thereby making an implant suitable for intraocular use.

13. The process of claim 12, wherein the cyclic lipid therapeutic agent component is selected from the group consisting of prostaglandins, prostaglandin analogs, and mixtures thereof.

14. The process of claim 12 wherein the cyclic lipid therapeutic agent is selected from the group consisting of bimatoprost, bimatoprost analogs, and mixtures thereof.

15. The process of claim 12 wherein the first biodegradable polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polylactide-co-glycolide, and copolymers thereof.

16. The process of claim 12 wherein the second biodegradable polymer is selected from the group consisting of decafluorobutane, poly(isobutylene), poly(hexemethylene adipamide), poly propylene, poly ethylene and polyethylne glycol.

17. The process of claim 12 wherein the solubilities of the cyclic lipid therapeutic agent, the first biodegradable polymer, and the second biodegradable polymer are all within about 10 Mpa^1/2 of each other.

18. The process of claim 12 wherein the solubilities of the cyclic lipid therapeutic agent, the first biodegradable polymer, and the second biodegradable polymer are all within about 15 to 30 Mpa^1/2.

19. The process of claim 12 wherein the first polymer comprises from about 30% to about 90% by weight of the implant.

20. The process of claim 12 wherein the second polymer comprises from about 50% to about 30% by weight of the implant.

21. The process of claim 12 wherein the cyclic lipid therapeutic agent comprises from about 5% to about 30% by weight of the implant.

22. A process for making an intraocular implant, the process comprising the steps of:

(a) combining;

(i) a prostaglandin analog, wherein the prostaglandin analog comprises from about 5% to about 30% by weight of the implant;

(ii) a poly(lactide-co-glycolide) copolymer, wherein the poly(lactide-co-glycolide) comprises from about 30% to about 90% by weight of the implant. and;

(ii) a second biodegradable polymer to form a mixture, wherein the second biodegradable polymer comprises from about 5% to about 40% by weight of the implant, and wherein;

(α

) the a poly(lactide-co-glycolide) copolymer and the second biodegradable polymer are different polymers;

(β

) the solubilities of the prostaglandin analog, the poly(lactide-co-glycolide) copolymer, and the second biodegradable polymer are all within about 10 Mpa^1/2 of each other, and;

(γ

) the melt temperature of the second biodegradable polymer is lower than the melting point of the a poly(lactide-co-glycolide) copolymer,

(b) heating the mixture to the lower melt temperature of the second biodegradable polymer, so that the second biodegradable polymer can function as a solvent for the prostaglandin analog and for the a poly(lactide-co-glycolide) copolymer, and;

(c) extruding the heated mixture, thereby making an implant suitable for intraocular use, wherein the prostaglandin analog released from the implant has a potency of at least about 50%.