Corticosteroids for the treatment of joint pain
View Patent ↗Corticosteroid microparticle formulations are provided for use for treating pain, including pain caused by inflammatory diseases such as osteoarthritis or rheumatoid arthritis, and for slowing, arresting or reversing structural damage to tissues caused by an inflammatory disease, for example damage to articular and/or peri-articular tissues caused by osteoarthritis or rheumatoid arthritis. Corticosteroid microparticle formulations are administered locally as a sustained release dosage form (with or without an immediate release component) that results in efficacy accompanied by clinically insignificant or no measurable effect on endogenous cortisol production.
1. An injectable formulation comprising (a) controlled- or sustained-release microparticles comprising triamcinolone acetonide (TCA) or a pharmaceutically-acceptable salt thereof and a poly(lactic-co-glycolic) acid copolymer (PLGA) matrix, wherein the TCA comprises between 22% to 28% of the microparticles and wherein the PLGA has the following characteristics: (i) a molecular weight in the range of about 40 to 70 kDa; and (ii) a lactic acid:glycolic acid molar ratio of 80:20 to 60:40, and wherein the TCA is released for between at least 14 days and 90 days upon administration to a joint.
2. The formulation of claim 1 , wherein the PLGA copolymer has a molar ratio of lactic acid:glycolic acid of 75:25.
3. The formulation of claim 1 , wherein the microparticles further comprise a polyethylene glycol (PEG) moiety, wherein the PEG moiety comprises between 25% to 0% weight percent of the microparticle.
4. The formulation of claim 1 , wherein the 22% to 28% of TCA in the microparticles comprises a total TCA load dose between 10 to 50 mg.
5. The formulation of claim 1 , wherein the lactic acid-glycolic acid copolymer has an inherent viscosity in the range of 0.3 to 0.5 dL/g.
6. An injectable formulation comprising (a) controlled- or sustained-release microparticles comprising triamcinolone acetonide (TCA) or a pharmaceutically-acceptable salt thereof and a poly(lactic-co-glycolic) acid copolymer (PLGA) matrix, wherein the TCA comprises between 22% to 28% of the microparticles, wherein the microparticles have a mean diameter of between 10 μm to 100 μm, and wherein the PLGA has the following characteristics: (i) a molecular weight in the range of about 40 to 70 kDa; and (ii) a lactic acid:glycolic acid molar ratio of 80:20 to 60:40, wherein the TCA is released for between at least 14 days and 90 days upon administration to a joint.
7. The formulation of claim 6 , wherein the PLGA copolymer has a molar ratio of lactic acid:glycolic acid of 75:25.
8. The formulation of claim 6 , wherein the microparticles further comprise a polyethylene glycol (PEG) moiety, wherein the PEG moiety comprises between 25% to 0% weight percent of the microparticle.
9. The formulation of claim 6 , wherein the 22 to 28% of TCA in the microparticles comprises a total TCA load dose between 10 to 50 mg.
10. The formulation of claim 6 , wherein the lactic acid-glycolic acid copolymer has an inherent viscosity in the range of 0.3 to 0.5 dL/g.