Injectable sustained release composition and method of using the same for treating inflammation in joints and pain associated therewith
Described herein are injectable corticosteroid-loaded microparticles, pharmaceutical composition thereof and methods for reducing inflammation or pain in a body compartment such as a joint, an epidural space, a vitreous body of an eye, a surgically created space, or a space adjacent to an implant.
1. A method for making coated microparticles, comprising: providing crystalline drug cores of fluticasone propionate,
coating over each crystalline drug core of fluticasone propionate with polyvinyl alcohol to provide coated microparticles, wherein the polyvinyl alcohol forms a polymeric shell that surrounds or envelopes each crystalline drug core of fluticasone propionate; and
heating the coated microparticles at 210-230° C., wherein the coated microparticles have a mean diameter in the range of 75 um to 150 um and a standard deviation of less than 50% of the mean diameter.
2. The method of claim 1 wherein heating the coated microparticles comprises heating for at least one hour.
3. The method of claim 1 wherein providing the one or more crystalline drug cores comprises sizing a plurality of crystalline drug particles.
4. The method of claim 3 wherein the sizing utilizes 80-170 μm mesh sieve and 30-60 μm mesh sieve.
5. The method of claim 3 wherein the one or more crystalline drug cores obtained from sizing have mean diameters in the range of 50-100 μm.
6. The method of claim 1 wherein coating over each crystalline drug core is carried out in a fluidized bed coater system.
7. The method of claim 1 wherein the polyvinyl alcohol is applied to the crystalline drug cores of fluticasone propionate in a fluid form with a solvent, wherein the solvent is a mixture of isopropyl alcohol and water.
8. The method of claim 1 wherein each coated microparticle comprises 90-98% w/w of crystalline drug core and 2-10% w/w of polymeric shell.
9. A method for preparing coated fluticasone propionate microparticles, the method comprising: providing crystalline drug cores of fluticasone propionate, providing coated fluticasone propionate microparticles by fluidic bed coating which forms a polymeric shell of polyvinyl alcohol over each crystalline drug core of fluticasone propionate; and heating the coated fluticasone propionate microparticles at 210-230° C., wherein each coated fluticasone propionate microparticle consists of fluticasone propionate and polyvinyl alcohol, wherein the coated microparticles have a mean diameter in the range of 75 um to 150 um and a standard deviation of less than 50% of the mean diameter.
10. The method of claim 9 wherein heating the coated fluticasone propionate microparticles comprises heating for at least one hour.
11. The method of claim 9 wherein providing the crystalline drug cores comprises sizing a plurality of recrystallized particles of fluticasone propionate.
12. The method of claim 11 wherein the sizing utilizes 80-170 μm mesh sieve and 30-60 μm mesh sieve.
13. The method of claim 12 wherein the one or more crystalline drug cores of fluticasone propionate obtained from sizing have mean diameters in the range of 50-100 μm.