Methods for the preparation of injectable depot compositions
AssigneeLaboratorios Farmaceuticos Rovi, S.A.
InventorsIbon Gutierro Aduriz, Maria Teresa Gomez Ochoa
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Abstract
Injectable depot compositions comprising a biocompatible polymer which is a polymer or copolymer based on lactic acid and/or lactic acid plus glycolic acid having a monomer ratio of lactic to glycolic acid in the range from 48:52 to 100:0, a water-miscible solvent having a dipole moment of about 3.7-4.5 D and a dielectric constant of between 30 and 50, and a drug, were found suitable for forming in-situ biodegradable implants which can evoke therapeutic drug plasma levels from the first day and for at least 14 days.
Claims25
An injectable depot composition consisting of drug, which is risperidone, paliperidone, or a combination thereof, and a polymeric solution of DMSO and PLGA copolymer, and wherein:
- the content of said drug is 13% wt ±10%, based upon the weight of the composition, and said drug possesses a particle distribution selected from:
- a. not more than 10% of the total volume of the particles is smaller than 10 microns, not more than 10% of the total volume of particles is greater than 225 microns, and the d0.5 is in the range of 10-200 microns;
- b. not more than 10% of the total volume of the particles is less than the range 1-10 μm, not more than 10% of the total volume of particles is greater than the range 225-400 μm, and the d0.5 of the size distribution is in the range of about 40-200 μm;
- or
- c. expressed as volume, d0.9 is about 150 to about 400 μm, d0.5 is about 40 to about 200 μm and d0.1 is about 10 to about 60 μm;
- the mass ratio of DMSO to drug is 4.66±10%:1;
- the mass ratio of polymeric solution to drug is 6.66±10%:1;
- the PLGA copolymer is an end-capped biodegradable poly(lactide-co-glycolide) copolymer having a monomer ratio of lactic acid to glycolic acid of 50:50±10% and an inherent viscosity in the range of 0.20±10% dl/g to 0.50±10% dl/g as measured in chloroform at 25° C. at a concentration of 0.1% wt/v with an Ubbelohde size 0c glass capillary viscometer;
- the polymeric solution has a viscosity in the range of 0.5-3.0 Pa·s ±10%;
- and
- the amount of said drug dissolved in the injectable composition is ≤20% wt.
An injectable depot composition consisting of drug, which is risperidone, paliperidone, or a combination thereof, and a polymeric solution of DMSO and PLGA copolymer, and wherein:
- the content of said drug is 13% wt ±10%, based upon the weight of the composition, and said drug possesses a particle distribution selected from:
- a) not more than 10% of the total volume of the particles is smaller than 10 microns, not more than 10% of the total volume of particles is greater than 225 microns, and the d0.5 is in the range of 10-200 microns;
- b) not more than 10% of the total volume of the particles is less than the range 1-10 μm, not more than 10% of the total volume of particles is greater than the range 225-400 μm, and the d0.5 of the size distribution is in the range of about 40-200 μm;
- or
- c) expressed as volume, d0.9 is about 150 to about 400 μm, d0.5 is about 40 to about 200 μm and d0.1 is about 10 to about 60 μm;
- the mass ratio of DMSO to drug is 4.66±10%:1;
- the mass ratio of polymeric solution to drug is about 6.66±10%:1;
- the PLGA copolymer is an end-capped biodegradable poly(lactide-co-glycolide) copolymer having a monomer ratio of lactic acid to glycolic acid of 50:50±10% and an inherent viscosity in the range of 0.20±10% dl/g to 0.50±10% dl/g as measured in chloroform at 25° C. at a concentration of 0.1% wt/v with an Ubbelohde size 0c glass capillary viscometer;
- the polymeric solution has a viscosity in the range of 0.5-3.0 Pa·s ±10%;
- the amount of said drug dissolved in the injectable composition is ≤20% wt;
- at least one of said drug and PLGA copolymer has been irradiated with beta-irradiation in the range of 5-25 KGy;
- and
- the viscosity of the composition is in the range of 0.7-4.0 Pa·s ±10%.
Dependencies are inferred from the claim text.