Injectable composition with aromatase inhibitor
The present invention provides a composition suitable for forming an intramuscular implant. It comprises a biodegradable thermoplastic polymer of polylactic acid (PLA), DMSO and an aromatase inhibitor compound. The invention also provides a kit suitable for the in situ formation of the composition and its use as a medicine for treating cancer, especially breast cancer.
1. An injectable composition consisting of
about 25% wt of drug, which is letrozole, wherein the drug has a particle size distribution selected from any of the following
<10% of the particles are less than 20 microns, <10% of the particles are greater than 350 microns, and a d0.5 between 70-200 microns; or
d0.1 of 38.21 microns, d0.5 of 141.35 microns, and d0.9 of 312.13 microns; and
the remaining balance of said injectable composition comprising polymeric solution comprising
57-60% wt of DMSO; and
40-43% wt of biodegradable poly(lactic acid) polymer (PLA), wherein
the polymeric solution has a viscosity in the range of 0.8-1.5 Pa·s, as measured at 25° C.
2. The composition of claim 1 , wherein the PLA has been irradiated with a maximum dose of 35 kGy.
3. The injectable depot composition of claim 1 , wherein the maximum volume of the injectable depot composition is 2 mL containing a maximum of 500 mg of the drug.
4. The injectable depot composition of claim 1 , wherein, following administration to a subject, the AUC of the burst of drug is less than about 10% of the total AUC after administration and not more than about 50% of the total AUC over the first 30 days after administration.
5. A kit suitable for the in situ preparation of the injectable depot composition of claim 1 , wherein prior to administration the kit comprises the drug and the polymer in solid form in a first container, and the DMSO is in a second separate container.
6. The kit of claim 5 , wherein the polymer has been lyophilised.
7. A kit suitable for the in situ preparation of the injectable depot composition of claim 1 , wherein prior to administration the kit comprises the drug in a first container in solid form and the DMSO and the polymer in a second container in solution.
8. A kit suitable for the in situ preparation of the composition of claim 1 , wherein prior to administration the kit comprises the drug, the polymer and the DMSO in a single container in the form of a suspension.
9. The composition of claim 1 , wherein the PLA is end-capped with a carboxylic acid group.
10. The injectable composition of claim 1 , wherein the PLA is end-capped with an ester group.