Sustained release polymer
A polymer and a method for its preparation are provided. The polymer comprises poly(lactide), poly(lactide/glycolide) or poly(lactic acid/glycolic acid) segments bonded by ester linkages to both ends of an alkanediol core unit. The polymer is for use in a controlled release formulation for a medicament, preferably leuprolide acetate. The controlled release formulation is administered to a patient as a subcutaneous depot of a flowable composition comprising the polymer, a biocompatible solvent, and the medicament. Controlled release formulations comprising the polymer release leuprolide for treatment of prostate cancer patients over periods of 3-6 months.
1. A polymer of Formula (I/II):
wherein:
wherein L/G signifies a PLG copolymer segment, the H atoms at both distal ends signify the hydrogen atoms borne by the terminal hydroxyl groups, and R a is an alkylene diradical;
R b and R c are either hydrogen or methyl;
the polymer is substantially insoluble in water and body fluid,
the polymer has substantially no titratable carboxylic acid groups, the polymer has a weight average molecular weight from about 10 kD to about 50 kD, and the polymer in neat form is a solid at ambient temperature.
2. The polymer of claim 1 wherein L/G comprises a lactide/glycolide copolymer segment with a lactide/glycolide ratio of about 45/55 to about 99/1.
3. The polymer of claim 1 wherein L/G comprises a lactide/glycolide copolymer segment with a lactide/glycolide ratio of about 70/30 to about 90/10.
4. The polymer of claim 1 having a weight average molecular weight of about 8 kD to about 100 kD.
5. The polymer of claim 4 having a weight average molecular weight of about 10 kD to about 50 kD.
6. The polymer of claim 4 having a weight average molecular weight of about 15 kD to about 45 kD.
7. The polymer of claim 4 wherein R a is a linear unsubstituted carbon chain.
8. The polymer of claim 7 wherein R a is a linear unsubstituted carbon chain of 6 carbon atoms.
9. The polymer of claim 4 wherein a polydispersity of the polymer is about 1.2 to about 2.0.
10. The polymer of claim 4 wherein a polydispersity of the polymer is about 1.4 to about 1.7.
11. The polymer of claim 4 wherein an inherent viscosity of the polymer is about 0.20 dL/gm to about 0.60 dL/gm.
12. The polymer of claim 4 wherein an inherent viscosity of the polymer is about 0.25 dL/gm to about 0.40 dL/gm.