Pharmaceutical compositions with enhanced stability
The present invention provides for a stabilized biodegradable polymeric composition useful as a controlled release delivery system for peptide agents. The compositions of the present invention comprise a) a beneficial salt of a peptide agent formed with a strong acid that minimizes or prevents the interaction/reaction between the peptide agent and the polymer in an organic solution; b) a biodegradable polymer; c) a pharmaceutically acceptable organic solvent; and d) optionally one or more excipients. The present invention also relates to a method of manufacturing and a method of use thereof.
1. An injectable polymeric composition comprising:
a) a mesylate salt of leuprolide;
b) a biodegradable polymer selected from the group of polylactide, poly(lactic acid), poly(lactic acid-co-glycolic acid), and poly(lactide-co-glycolide); and
c) N-methyl-2-pyrrolidone (NMP),
wherein the composition does not contain excess strong acid in addition to the strong acid used to form the mesylate salt of leuprolide.
2. The injectable polymeric composition of claim 1 , wherein the biodegradable polymer has a weight average molecular weight of between about 2,000 to about 100,000 dalton.
3. The injectable polymeric composition of claim 1 comprising:
a) 0.01-40% w/w leuprolide mesylate;
b) 40-60% w/w the biodegradable polymer selected from the group consisting of polylactide and poly(lactic acid); and
c) 30-80% w/w N-methyl-2-pyrrolidone,
wherein the composition does not contain excess strong acid in addition to the strong acid used to form the leuprolide mesylate.
4. The injectable polymeric composition of claim 3 , wherein the biodegradable polymer has an average molecular weight of about 8,000 to about 50,000.
5. An injectable polymeric composition of claim 1 comprising:
a) 0.01-40% w/w leuprolide mesylate;
b) 30-60% w/w biodegradable polymer selected from the group consisting of poly(lactide-co-glycolide) and poly(lactic acid-co-glycolic acid), having the ratio of lactide:glycolide or lactic acid:glycolic acid of from 50:50 to about 100:0; and
c) 30-80% w/w N-methyl-2-pyrrolidone,
wherein the composition does not contain excess strong acid in addition to the strong acid used to form the leuprolide mesylate.
6. The injectable polymeric composition of claim 5 , wherein the poly(lactide-co-glycolide) or poly(lactic acid-co-glycolic acid) has a ratio of lactide:glycolide or lactic acid:glycolic acid of about 85:15.
7. The injectable polymeric composition of claim 5 , wherein the poly(lactide-co-glycolide) or poly(lactic acid-co-glycolic acid) has an average molecular weight of about 15,000 to about 50,000.