Injectable sustained release composition and method of using the same for treating inflammation in joints and pain associated therewith

Abstract

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.

We claim: 
     
         1 . A method of decreasing inflammation or managing pain in a patient in need thereof comprising administering to the patient, via injection to a body compartment, a therapeutically effective amount of a pharmaceutical composition comprising a plurality of microparticles and a pharmaceutically acceptable vehicle, each microparticle including:
 (1) a drug core of more than 70% by weight of the microparticle, the drug core having one or more crystals of a corticosteroid; and   (2) a polymeric shell encapsulating the drug core, wherein the polymeric shell is in contact but immiscible with the drug core, and wherein the polymeric shell comprises one or more cross-linked polymers.   
     
     
         2 . The method of  claim 1  wherein the microparticles have a mean diameter in the range of 50-100 μm. 
     
     
         3 . The method of  claim 1 , wherein the one or more crystals of the corticosteroid are crystals of fluticasone, fluticasone furoate, and fluticasone propionate, or a combination thereof. 
     
     
         4 . The method of  claim 1  wherein administering the pharmaceutical composition comprises injecting, intra-articularly, to an affected joint of said patient. 
     
     
         5 . The method of  claim 4  wherein the inflammation or pain in a patient is due to at least one of osteoarthritis, rheumatoid arthritis or injury induced arthritis. 
     
     
         6 . The method of  claim 1  wherein administering comprises injecting the pharmaceutical composition into an epidural space of said patient. 
     
     
         7 . The method of  claim 6  wherein the inflammation or pain in a patient is due to at least one of spinal disc protrusion, spinal nerve inflammation in cervical, thoracic or lumbar, chronic low back pain from nerve root compression. 
     
     
         8 . The method of  claim 1  wherein administering comprises injecting the pharmaceutical composition into vitreous humour of the patient. 
     
     
         9 . The method of  claim 8  wherein the inflammation or pain in a patient is due to diabetic macular edema or uveitis. 
     
     
         10 . The method of  claim 1  wherein administering comprises injecting the pharmaceutical composition into a space adjacent to an implant having scar tissue. 
     
     
         11 . The method of  claim 10  wherein the inflammation or pain in the patient is due to recurrent capsular contractions or keloid scarring. 
     
     
         12 . The method of  claim 1 , wherein said drug core of each microparticle comprises substantially pure corticosteroid, which constitutes at least 90% of the microparticle by weight. 
     
     
         13 . The method  claim 1  wherein the polymeric shell comprises at least one of polylactic acid, polyvinyl alcohol, ethylene vinyl acetate and parylene. 
     
     
         14 . The method of  claim 1  wherein said microparticles when dissolution tested using United States Pharmacopoeia Type II apparatus exhibit a dissolution half-life of 12-20 hours, wherein the dissolution conditions are: 3 milligrams of microparticles in 200 milliliters of dissolution medium of 70% v/v methanol and 30% v/v of water at 25° C. 
     
     
         15 . The method of  claim 1  wherein the microparticles are heat-treated prior to being formulated into the pharmaceutical composition. 
     
     
         16 . The method of  claim 1  wherein the sustained release of the corticosteroid lasts for 2-12 months. 
     
     
         17 . A method of decreasing inflammation or managing pain in a patient in need thereof comprising:
 administering to the patient, via a single injection to a body compartment, a unit dosage form for sustained release of a corticosteroid wherein the unit dosage form comprises a plurality of microparticles and a pharmaceutically acceptable vehicle,   wherein the crystalline drug core includes one or more crystals of a corticosteroid selected from fluticasone, fluticasone furoate, and fluticasone propionate, and the polymeric shell is in contact but immiscible with the crystalline drug core,   and wherein, following the single injection, the corticosteroid is released over a period of 2-12 months while maintaining a minimum therapeutically effective concentration of the corticosteroid within the body compartment.   
     
     
         18 . The method of  claim 17  wherein the body compartment is a joint, epidural space, intravitreal space, a surgically created space, or a space near an implant having scar tissue. 
     
     
         19 . The method of  claim 17  wherein, within the sustained release period of 2-12 months, the corticosteroid is released locally within the body compartment and provides plasma corticosteroid below a quantifiable limit 7 days after injection. 
     
     
         20 . The method of  claim 17  further comprising, after the period of 2-12 months, administering a further unit dosage form for sustained release of the corticosteroid.