Methods for treating ocular conditions with cyclic lipid containing microparticles

• US 20060246145A1
• Filed: 03/08/2006
• Published: 11/02/2006
• Est. Priority Date: 04/30/2004
• Status: Active Grant

• Current Assignee: Allergan Incorporated (Abbvie Incorporated)
• Original Assignee: Allergan Incorporated (Abbvie Incorporated)
• Inventors: Chang, Chin-Ming, Chang, James, Hughes, Patrick
• Granted Patent: US 8,722,097 B2
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• 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 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• 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 9/146 with organic macromolecular compounds
• 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: B01J 13/04 by physical processes, e.g. drying, spraying
• CPC Class Codes: B01J 13/06 by phase separation

Abstract

Biocompatible microparticles include an ophthalmically active cyclic lipid component and a biodegradable polymer that is effective, when placed into the subconjunctival space, in facilitating release of the cyclic lipid component into the anterior and posterior segments of an eye for an extended period of time. The cyclic lipid component can be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the cyclic lipid component can be encapsulated by the polymeric component. The present microparticles include oil-in-water emulsified microparticles. The subconjunctivally administered microparticles can be used to treat or to reduce at least one symptom of an ocular condition, such as glaucoma or age related macular degeneration.

Claims

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

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

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

(a) combining a PLGA with bimatoprost in an organic solvent to form an oil phase;

(b) adding a second organic solvent with an excess amount of bimatoprost to thereby form a saturated aqueous phase;

(c) emulsifying the oil phase the aqueous phase by mixing the two phases together to thereby form bimatoprost loaded microspheres, and;

(d) removing first and second organic solvents from the microspheres.

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 latanoprost.

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-water 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-water 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.