Injectable composition with aromatase inhibitor

• US 10,285,936 B2
• Filed: 01/30/2015
• Issued: 05/14/2019
• Est. Priority Date: 05/31/2010
• Status: Active Grant

• Current Assignee: Laboratorios Farmaceuticos Rovi, S.A. (Norbel Inversiones SL)
• Original Assignee: Laboratorios Farmaceuticos Rovi, S.A. (Norbel Inversiones SL)
• Inventors: Franco Rodriguez, Guillermo, Gutierro Aduriz, Ibon
• Primary Examiner(s): Peebles, Katherine
• Application Number:
  US14/610,362
• Publication Number:
  US 20150196485A1
• Time in Patent Office: 1,565 Days
• Field of Search: None
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L

Abstract

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.

Claims

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.