Pharmaceutical compositions of goserelin sustained release microspheres

Abstract

A composition of goserelin sustained release microspheres is provided. The microspheres comprise goserelin, at least one poly(lactide-co-glycolide) and poloxamer or PEG. The sustained release microspheres have comparatively high bioavailability, which promotes the drug taking its full effect and have entrapment efficiency over 90%.

What is claimed is: 
     
         1 . A pharmaceutical composition of sustained release goserelin microspheres, comprising (a) goserelin or a salt thereof, (b) poly(lactide-co-glycolide), and (c) poloxamer or polyethylene glycol (PEG). 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the poloxamer is poloxamer 188 or poloxamer 407. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the PEG is PEG 2000, PEG 4000 or PEG 6000. 
     
     
         4 . The pharmaceutical composition according to  claim 2 , wherein the content by weight of poloxamer or PEG is within a range from 1% to 10%. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the content by weight of the goserelin or a salt thereof is within a range from 1% to 10%. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the molar ratio of lactide to glycolide in the poly(lactide-co-glycolide) is within a range from 90:10 to 10:90. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the poly(lactide-co-glycolide) has an intrinsic viscosity of 0.10-0.40 dl/g. 
     
     
         8 . The pharmaceutical composition according to  claim 1 , wherein the weight average molecular weight of the poly(lactide-co-glycolide) is 4,000-45,000 Dalton. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein the weight content of the poly(lactide-co-glycolide) is 80-98%. 
     
     
         10 . The pharmaceutical composition according to  claim 1 , further comprising (d) acetic acid. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein the weight content of the acetic acid is less than 0.1%. 
     
     
         12 . The pharmaceutical composition according to  claim 11 , wherein the weight content of the acetic acid is less than 0.01%. 
     
     
         13 . The pharmaceutical composition according to  claim 1 , wherein the weight content of the goserelin is 1-10%; wherein the weight content of the poly(lactide-co-glycolide) is 80-98%; and wherein the weight content of the poloxamer or PEG is 1-10%. 
     
     
         14 . The pharmaceutical composition according to  claim 1 , wherein the weight content of the goserelin is 1-8%; wherein the weight content of the poly(lactide-co-glycolide) is 86-98%; and wherein the weight content of the poloxamer or PEG is 1-6%. 
     
     
         15 . The pharmaceutical composition according to  claim 1 , wherein the weight content of the goserelin is 1-5%; wherein the weight content of the poly(lactide-co-glycolide) is 91-98%; and wherein the weight content of poloxamer or PEG is 1-4%. 
     
     
         16 . A method for preparing the pharmaceutical composition of  claim 1 , wherein the composition is prepared by a solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation method, comprising pre-treating goserelin acetate with poloxamer or PEG, and then adding the pretreated goserelin acetate to an oil phase comprising poly(lactide-co-glycolide). 
     
     
         17 . The method of  claim 16 , wherein the poloxamer or PEG pre-treated goserelin acetate in the oil phase has a particle size d (0.5) of 0.01-2 μm. 
     
     
         18 . A method for treating prostate cancer, sexual precocity, adenomyosis, female infertility, or hysteromyoma in a subject in need thereof, comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 1 .