Sustained release formulations comprising gnrh analogues

Abstract

The present invention relates to pharmaceutical compositions for the controlled and sustained release of active substance comprising a biodegradable polymer or copolymer. Furthermore, the invention relates to pharmaceutical compositions for the controlled and sustained release of at least one active substance such as peptides or hormones and analogues thereof and the manufacturing process of such pharmaceutical compositions.

1 . An elongated implant for the controlled and sustained release of at least one GnRH analogue, the implant comprising a biodegradable polymeric or co-polymeric sleeve and, in the sleeve, a polymeric or co-polymeric core comprising at least a GnRH analogue, characterized in that
 at least one end of the sleeve is open, and   the sleeve degrades during the sustained release.   
     
     
         2 . The implant of  claim 1  wherein the GnRH analogue is a triptorelin salt preferably triptorelin acetate or triptorelin pamoate, more preferably triptorelin acetate. 
     
     
         3 . The implant of  claim 2  wherein the amount of triptorelin acetate in the polymeric or co-polymeric core is within the range of 30 to 90% by weight relative to the total weight of the polymeric or co-polymeric core, preferably within the range of 35 to 65% by weight relative to the total weight of the polymeric or co-polymeric core. 
     
     
         4 . The implant of any one of  claims 1  to  3  wherein the polymeric or co-polymeric sleeve and the polymeric or co-polymeric core are made from the same polymer or co-polymer. 
     
     
         5 . The polymer or co-polymer of  claim 4  is a poly(lactide-co-glycolide) acid (PLGA) in a ratio of lactic acid to glycolic acid in the PLGA within the range of 70:30 to 90:10, preferably, the ratio of lactic acid to glycolic acid in the PLGA is 85:15. 
     
     
         6 . The implant of any one of  claims 1  to  5  is suitable for the release of the GnRH analogue for at least 3 months, preferably at least 6 months. 
     
     
         7 . The implant of anyone of  claims 2  to  6  wherein the triptorelin acetate is present in an amount within the range of 0.5 to 50 mg, preferably present in an amount within the range of 2 to 20 mg, more preferably in an amount of 5, 6, 7, 8, 9 or 10 mg. 
     
     
         8 . The implant of any one of  claims 1  to  7  wherein the axial length of the implant is between 2 and 3 cm, preferably the axial length of the implant is approximately 2.6 cm. 
     
     
         9 . The implant of any one of  claims 1  to  8  wherein the ratio of the diameter to axial length of the implant is between 1:20 and 1:40, preferably the ratio of the diameter to axial length of the implant is 1:30. 
     
     
         10 . The implant of any one of  claims 1  to  9  wherein the PLGA has a molecular mass of at least 60 kDa, preferably the PLGA has a molecular mass of at least 100 kDa. 
     
     
         11 . A process for the preparation of an elongated implant, comprising the steps of
 combining a GnRH analogue and a polymer or co-polymer, and   subsequently, co-extruding the combination and a biodegradable polymer or co-polymer,   to form an implant comprising a GnRH analogue and polymeric or co-polymeric core inside a biodegradable polymeric or co-polymeric sleeve.   
     
     
         12 . An elongated implant obtainable by the process of  claim 11 . 
     
     
         13 . An elongated implant for the controlled and sustained release of the GnRH analogue triptorelin acetate, the implant comprising
 a polymeric or co-polymeric sleeve having at least one open end, and   in the sleeve, a core comprising the triptorelin acetate.   
     
     
         14 . A process for the preparation of an elongated implant, comprising the steps of
 preparing a polymeric or co-polymeric sleeve,   preparing a solution of between 40 and 80% (w/w) triptorelin acetate in water,   placing the solution in the sleeve,   incubating the solution for 2-48 h at 20-30° C., and   drying for 6-24 h under vacuum.   
     
     
         15 . A process for the preparation of an elongated implant, comprising the step of
 introducing of pellets made of biodegradable polymer or copolymer and active substance in the core extruder   extruding the core made of biodegradable polymer or copolymer and active substance and thereafter cooling   coating with a biodegradable polymer or copolymer.