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US 2025/0144218 A1Published application
Injectable composition
AssigneeLaboratorios Farmaceuticos Rovi, S.A.
InventorsGUILLERMO FRANCO RODRIGUEZ, IBON GUTIERRO ADURIZ
Life of this patent
Estimating the term…
Abstract
An injectable depot composition suitable for forming an in situ intramuscular implant is provided. The composition includes sterile biodegradable thermoplastic polymer of polylactic acid (PLA), solvent for the PLA, and drug. After administration to a subject, a corresponding implant administers 0.1-2 milligrams of nonsteroidal aromatase inhibitor every day throughout a dosing period of about six months to about one year. The composition is used to treat subjects in need thereof.
Claims28
A method of treating a disease, disorder or condition that is therapeutically responsive to nonsteroidal inhibitor of aromatase, said method comprising
- a. providing a kit comprising components for preparing an injectable depot composition;
- b. mixing components of the kit to form said injectable depot composition;
- and
- c. administering said injectable depot composition to a subject in need thereof;
- wherein
- the kit comprises the components PLA (polylactic acid) particles, solvent for PLA, and drug particles, wherein prior to mixing the PLA particles, solvent for PLA, and drug particles, the drug has a particle size distribution that approximates the PLA's particle size distribution, and after mixing the PLA, solvent for PLA, and drug, the PLA is dissolved in the solvent, wherein the solvent is dimethyl sulfoxide (DMSO), and said drug is nonsteroidal inhibitor of aromatase selected from the group consisting of letrozole, anastrozole, salt of either thereof, and metabolite of either thereof, and further wherein prior to mixing the PLA particles with said solvent for PLA, the particle size distribution of the PLA particles is defined as follows:
- i. particle size mass distribution with not more than 10% above 300 microns when measured by analytical sieving according to USP<786>;
- ii. particle size mass distribution with not more than 10% above 250 microns when measured by analytical sieving according to USP<786>;
- iii. particle size volume distribution with a D90 not above 330 microns when measured by laser diffraction analysis;
- iv. particle size volume distribution with a D90 not above 280 microns when measured by laser diffraction analysis;
- v. particle size mass distribution where not more than 80% of the particles have a particle size below 125 microns, when measured by analytical sieving according to USP<786>;
- vi. a particle size volume distribution with a D80 not below 135 microns when measured by laser diffraction analysis;
- vii. particle size mass distribution with not more than 10% above 300 microns, and where not more than 80% of the particles have a particle size below 125 microns, when measured by analytical sieving according to USP<786>;
- and/or
- viii. particle size volume distribution with a D90 not above 330 microns, when measured by laser diffraction analysis and with a D80 not below 135 microns when measured by laser diffraction analysis.
12 more elements
A method of treating a disease, disorder or condition that is therapeutically responsive to nonsteroidal inhibitor of aromatase, said method comprising
- a. providing a kit comprising components for preparing an injectable depot composition;
- b. mixing components of the kit to form said injectable depot composition;
- and
- c. administering said injectable depot composition to a subject in need thereof;
- wherein
- d. the kit comprises the components PLA (polylactic acid) particles, dimethyl sulfoxide (DMSO), and letrozole particles, wherein prior to mixing the PLA particles, DMSO, and letrozole particles, the letrozole has a particle size distribution that approximates the PLA's particle size distribution, and after mixing the PLA particles, DMSO, and letrozole particles, the PLA is dissolved in the solvent, and wherein:
- i. prior to mixing the PLA particles with said solvent for PLA, the PLA particle size distribution is defined as a particle size mass distribution with not more than 10% above 300 microns, and where not more than 80% of the particles have a particle size below 125 microns, when measured by analytical sieving according to USP<786>;
- and
- ii. implant(s) formed in a subject after administration of said injectable depot composition provides the following pharmacokinetic performance:
- Dose of drug administered
- About 50
- About 100
- (mg)
- Daily Plasma Concentration
- About 4.5 (about
- About 8.8 (about
- from about 2 days after
- 0.5 to about 13)
- 1.5 to about 21)
- administration (ng/mL)
- Cmax (ng/mL)
- About 5
- About 11
- Tlag (h)
- 0 h
- 0 h
23 more elements
A method of treating a disease, disorder or condition that is therapeutically responsive to nonsteroidal inhibitor of aromatase, said method comprising administering to a subject in need thereof an injectable depot composition consisting essentially of
- a. 15-35 wt. % letrozole, 25-35 wt. % PLA, and 30-60 wt. % dimethyl sulfoxide (DMSO);
- b. 18-28 wt. % letrozole, 30-35 wt. % PLA, and 37-52 wt. % DMSO;
- or
- c. about 23 to about 27 wt. % letrozole, about 28 to about 34 wt. % PLA, and about 41 to about 47 wt. % DMSO;
- wherein the weight percentages are with respect to the total weight of said composition, and prior to formation of said injectable composition, the PLA is comprised of particles having a particle size mass distribution with not more than 10% above 300 microns, and where not more than 80% of the particles have a particle size below 125 microns, when measured by analytical sieving according to USP<786>.
2 more elements
A method of treating a disease, disorder or condition that is therapeutically responsive to nonsteroidal inhibitor of aromatase, said method comprising administering an injectable depot composition to a subject in need thereof;
- wherein said injectable depot composition comprises PLA (polylactic acid) particles, solvent for PLA, and drug particles;
- and wherein prior to formation of said injectable depot composition the drug has a particle size distribution that approximates the PLA's particle size distribution, and after mixing the PLA, solvent for PLA, and drug, the PLA is dissolved in the solvent;
- and further wherein the solvent is dimethyl sulfoxide (DMSO), and said drug is nonsteroidal inhibitor of aromatase selected from the group consisting of letrozole, anastrozole, salt of either thereof, and metabolite of either thereof;
- and still further wherein prior to mixing the PLA particles with said solvent for PLA, the particle size distribution of the PLA particles is defined as follows:
- i. particle size mass distribution with not more than 10% above 300 microns when measured by analytical sieving according to USP<786>;
- ii. particle size mass distribution with not more than 10% above 250 microns when measured by analytical sieving according to USP<786>;
- iii. particle size volume distribution with a D90 not above 330 microns when measured by laser diffraction analysis;
- iv. particle size volume distribution with a D90 not above 280 microns when measured by laser diffraction analysis;
- v. particle size mass distribution where not more than 80% of the particles have a particle size below 125 microns, when measured by analytical sieving according to USP<786>;
- vi. a particle size volume distribution with a D80 not below 135 microns when measured by laser diffraction analysis;
- vii. particle size mass distribution with not more than 10% above 300 microns, and where not more than 80% of the particles have a particle size below 125 microns, when measured by analytical sieving according to USP<786>;
- and/or
- viii. particle size volume distribution with a D90 not above 330 microns, when measured by laser diffraction analysis and with a D80 not below 135 microns when measured by laser diffraction analysis.
10 more elements
A method of treating a disease, disorder or condition that is therapeutically responsive to nonsteroidal inhibitor of aromatase, said method comprising administering an injectable depot composition to a subject in need thereof;
- wherein said injectable depot composition comprises PLA (polylactic acid) particles, dimethyl sulfoxide (DMSO), and letrozole particles, wherein prior to formation of said injectable depot composition, the letrozole has a particle size distribution that approximates the PLA's particle size distribution, and after mixing the PLA particles, DMSO, and letrozole particles, the PLA is dissolved in the solvent, and further wherein:
- a. prior to mixing the PLA particles with said solvent for PLA, the PLA particle size distribution is defined as a particle size mass distribution with not more than 10% above 300 microns, and where not more than 80% of the particles have a particle size below 125 microns, when measured by analytical sieving according to USP<786>;
- and
- b. implant(s) formed in a subject after administration of said injectable depot composition provides the following pharmacokinetic performance:
- Dose of drug administered
- About 50
- About 100
- (mg)
- Daily Plasma Concentration
- About 4.5 (about
- About 8.8 (about
- from about 2 days after
- 0.5 to about 13)
- 1.5 to about 21)
- administration (ng/mL)
- Cmax (ng/mL)
- About 5
- About 11
- Tlag (h)
- 0 h
- 0 h
18 more elements
Dependencies are inferred from the claim text.