Oil-in-oil emulsified polymeric implants containing a hypotensive lipid and related methods

• US 20070224246A1
• Filed: 12/15/2005
• Published: 09/27/2007
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Original Assignee: Allergan, Inc. (Canada) (Abbvie Incorporated)
• Inventors: Sarrazin, Christian, Boix, Michele, Do, Marina, Hughes, Patrick
• Granted Patent: US 7,993,634 B2
• Time in Patent Office: Days
• US Class Current: 424/427
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• 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 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61L 2/081 Gamma radiation
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B01J 13/04 by physical processes, e.g. drying, spraying
• CPC Class Codes: B01J 13/06 by phase separation

Abstract

Biocompatible intraocular implants, such as microparticles, include a prostamide component and a biodegradable polymer that is effective in facilitating release of the prostamide component into an eye for an extended period of time. The prostamide component may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the prostamide component may be encapsulated by the polymeric component. The present implants include oil-in-oil emulsified implants or microparticles. Methods of producing the present implants are also described. The implants may be placed in an eye to treat or reduce a at least one symptom of an ocular condition, such as glaucoma.

Claims

1. A method for producing therapeutic polymeric microparticles, comprising:

encapsulating a prostamide component with a polymeric component to form a population of prostamide-encapsulated microparticles by an oil-in-oil emulsion process.

2. The method of claim 1, wherein the oil-in-oil emulsion process comprises

forming an oil-in-oil emulsion containing the prostamide component and the polymeric component;

drying the emulsion to form a dried emulsion product;

contacting the dried emulsion product with a solvent to form a solvent-containing composition; and

removing the solvent from the solvent-containing composition to form the population of microparticles comprising the prostamide component and the polymeric component.

3. The method of claim 1, wherein the prostamide component comprises a single type of a prostamide derivative.

4. The method of claim 1, wherein the prostamide component comprises at least one prostamide derivative selected from the group consisting of bimatoprost, salts thereof, and mixtures thereof.

5. The method of claim 1, wherein the prostamide component consists essentially of bimatoprost.

6. The method of claim 1, wherein the prostamide component comprises a combination of two or more different prostamide derivatives.

7. The method of claim 5, wherein the prostamide component comprises a combination of bimatoprost and iatanoprost.

8. The method of claim 5, wherein the prostamide component comprises a combination of bimatoprost and travoprost.

9. The method of claim 1, wherein the prostamide component of the microparticles so produced is encapsulated by the polymeric component to preserve therapeutic activity of the prostamide component after a terminal sterilization procedure.

10. The method of claim 1, wherein the polymeric component comprises a biodegradable polymer or biodegradable copolymer.

11. The method of claim 1, wherein the polymeric component comprises a poly(lactide-co-glycolide) PLGA copolymer.

12. The method of claim 1, wherein the PLGA copolymer has a lactide/glycolide ratio of 75/25 a molecular weight of about 63 kilodaltons, and an inherent viscosity of about 0.6 dL/g.

13. The method of claim 2, further comprising forming a first composition comprising the prostamide component, the polymeric component, and an organic solvent, and forming a second oil-containing composition, wherein the forming step comprises mixing the first composition and the second oil containing composition.

14. The method of claim 2, wherein the drying comprises evaporating the oil-in-oil emulsion to form an evaporated product.

15. The method of claim 14, further comprising suspending the evaporated product in the solvent before removing the solvent from the solvent-containing composition.

16. The method of claim 1, further comprising terminally sterilizing the polymeric microparticles.

17. A population of microparticles comprising a polymeric component encapsulating a prostamide component in the form of oil-in-oil emulsified microparticles.

18. The population of claim 17, wherein the polymeric component comprises a poly(lactide-co-glycolide) copolymer, and the prostamide component comprises at least one prostamide derivative selected from the group consisting of bimatoprost, salts thereof, and mixtures thereof.

19. The population of claim 17 which is terminally sterilized.

20. The population of claim 19, wherein at least 80% of the prostamide component remains stable after the sterilization.

21. The population of claim 17 having a mean particle diameter from about 30 μ

m to about 50 μ

m.

22. The population of claim 17, wherein the maximum particle diameter is less than about 200 μ

m.

23. The population of claim 17, wherein the microparticles have a release rate of the prostamide component of about 0.7% per day in vitro.

24. The population of claim 17, wherein the prostamide component comprises about 10% wt/wt of the microparticles.

25. The population of claim 17, wherein the prostamide component comprises about 5% wt/wt of the microparticles.

26. A method of treating an ocular condition in an eye of a patient, comprising the step of placing the population of claim 17 in an eye of a patient.

27. The method of claim 26 which is effective to treat glaucoma.

28. The method of claim 26 which is effective to decrease intraocular pressure.