Method of making oil-in-oil emulsified polymeric implants containing a hypotensive lipid
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.
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, wherein the prostamide component comprises a combination of two or more different prostamide derivatives.
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 of the microparticles so produced is encapsulated by the polymeric component to preserve therapeutic activity of the prostamide component after a terminal sterilization procedure.
4. The method of claim 1 , wherein the polymeric component comprises a biodegradable polymer or biodegradable copolymer.
5. The method of claim 1 , wherein the polymeric component comprises a poly(lactide-co-glycolide) PLGA copolymer.
6. The method of claim 5 , 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.
7. 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 the oil-in-oil emulsion step comprises mixing the first composition and the second oil containing composition.
8. The method of claim 2 , wherein the drying comprises evaporating the oil-in-oil emulsion to form an evaporated product.
9. The method of claim 8 , further comprising suspending the evaporated product in the solvent before removing the solvent from the solvent-containing composition.
10. The method of claim 1 , further comprising terminally sterilizing the polymeric microparticles.
11. The method of claim 1 , wherein the prostamide component comprises bimatoprost and latanoprost.
12. The method of claim 1 , wherein the prostamide component comprises bimatoprost and travoprost.