Methods for the preparation of injectable depot compositions
First Claim
1. A method of treating schizophrenia or bipolar disorder, the method comprising administering to a subject in need thereof an amount of injectable depot composition sufficient to provide a therapeutic dose of risperidone, to form an implant in the subject, wherein the injectable depot composition consists of risperidone, and a polymeric solution of DMSO and PLGA copolymer, and whereinthe content of risperidone is 13% wt±
- 10%, based upon the weight of the composition, and the risperidone possesses a particle distribution selected froma. 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 μ
m, not more than 10% of the total volume of particles is greater than the range 225-400 μ
m, and the d0.5 of the size distribution is in the range of about 40-200 μ
m;
orc. expressed as volume, d0.9 is about 150 to about 400 μ
m, d0.5 is about 40 to about 200 μ
m and d0.1 is about 10 to about 60 μ
m;
the mass ratio of DMSO to risperidone is 4.66±
10%;
1;
the mass ratio of polymeric solution to risperidone 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 0 c glass capillary viscometer;
the polymeric solution has a viscosity in the range of 0.5-3.0 Pa·
s±
10%; and
the amount of risperidone dissolved in the injectable composition is ≤
20% wt.
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Accused Products
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.
62 Citations
26 Claims
-
1. A method of treating schizophrenia or bipolar disorder, the method comprising administering to a subject in need thereof an amount of injectable depot composition sufficient to provide a therapeutic dose of risperidone, to form an implant in the subject, wherein the injectable depot composition consists of risperidone, and a polymeric solution of DMSO and PLGA copolymer, and wherein
the content of risperidone is 13% wt± - 10%, based upon the weight of the composition, and the risperidone 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 μ
m, not more than 10% of the total volume of particles is greater than the range 225-400 μ
m, and the d0.5 of the size distribution is in the range of about 40-200 μ
m;
orc. expressed as volume, d0.9 is about 150 to about 400 μ
m, d0.5 is about 40 to about 200 μ
m and d0.1 is about 10 to about 60 μ
m;the mass ratio of DMSO to risperidone is 4.66±
10%;
1;the mass ratio of polymeric solution to risperidone 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 0 c glass capillary viscometer;the polymeric solution has a viscosity in the range of 0.5-3.0 Pa·
s±
10%; andthe amount of risperidone dissolved in the injectable composition is ≤
20% wt. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
- 10%, based upon the weight of the composition, and the risperidone possesses a particle distribution selected from
Specification