Drug delivery formulations
The present invention is directed to methods of treating psychiatric diseases and disorders comprising administering to a subject in need thereof an injectable formulation comprising risperidone, triblock and diblock copolymers wherein the concentration of the risperidone is 250-400 mg/mL and injection volume is 1 mL or less.
1. A method of treating a psychiatric disease or disorder in a subject, comprising subcutaneously administering to the subject with a frequency of no more than once every 21 days:
1 mL or less of a pharmaceutical formulation comprising:
a) risperidone, or a pharmaceutically acceptable salt thereof, at a concentration of about 250-400 mg/mL, equivalent to risperidone;
b) a biodegradable triblock copolymer having the formula:
poly(lactic acid) v -poly(ethylene glycol) w ,-poly(lactic acid) x
wherein v and x are the number of repeat units ranging from 24 to 682 and w is the number of repeat units ranging from 4 to 273 and v=x or v≠x;
c) a biodegradable diblock copolymer having the formula:
methoxy poly(ethylene glycol) y -poly(lactic acid) z ,
wherein y and z are the number of repeat units, wherein y is the number of repeat units ranging from 3 to 45 and z is the number of units ranging from 7 to 327; and
wherein the ratio of the biodegradable triblock copolymer of (b) and the biodegradable diblock copolymer of (c) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19, in said formulation, which is insoluble in an aqueous environment.
2. The method of claim 1 , wherein the risperidone is risperidone base.
3. The method of claim 1 , wherein the concentration of the risperidone or the pharmaceutically acceptable salt thereof, is 300 mg/mL to 400 mg/mL, equivalent to risperidone.
4. The method of claim 1 , wherein the triblock copolymer is present in an amount of about 3% to 20% (w/w %) of the total weight of the formulation.
5. The method of claim 4 , wherein the triblock copolymer is present in an amount of about 5% to 15% (w/w %) of the total weight of the formulation.
6. The method of claim 1 , wherein the diblock copolymer is present in an amount of about 8% to 25% (w/w %) of the total weight of the formulation.
7. The method of claim 6 , wherein the diblock copolymer is present in an amount of about 10% to 20% (w/w %) of the total weight of the formulation.
8. The method of claim 1 , wherein the triblock and diblock copolymers are present in a total amount of about 20% to about 50% (w/w %) of the total weight of the formulation.
9. The method of claim 8 , wherein the triblock and diblock copolymers are present in a total amount of about 20% to 30% (w/w %) of the total weight of the formulation.
10. The method of claim 1 , wherein the formulation further comprises a water soluble organic solvent that is DMSO.
11. The method of claim 10 , wherein the formulation further comprises triacetin, tripropionin, or a mixture thereof.
12. The method of claim 10 , wherein the organic solvent is present in an amount of about 35% to about 55% (w/w %) of the total weight of the formulation.
13. The method of claim 1 , wherein the administration is effective in treating the subject's psychiatric disease or disorder for 21 days to 90 days.
14. The method of claim 1 , wherein the administration is effective in treating the subject's psychiatric disease or disorder for 28 days to 90 days.
15. The method of claim 1 , wherein the administration is effective in treating the subject's psychiatric disease or disorder for 28 days to 56 days.
16. The method of claim 1 , wherein less than about 15 w % of the risperidone in the formulation is cumulatively released at 24 hours post administration.
17. The method of claim 16 , wherein about 7 w % to about 15 w % of the risperidone in the formulation is cumulatively released at 24 hours post administration.
18. The method of claim 13 , wherein about 50 w % to about 80 w % of the risperidone in the formulation is cumulatively released at 30 days post administration.
19. The method of claim 13 , wherein about 70 w % to about 98% w % of the risperidone in the formulation is cumulatively released at 60 days administration.
20. The method of claim 13 , wherein the cumulative release is determined by in vitro release (IVR) method disclosed herein.
21. The method of claim 1 , wherein the psychiatric disease or disorder is schizophrenia or bipolar disorder.
22. The method of claim 1 , wherein the method is implemented in the absence of a loading dose or supplemental oral risperidone.
23. The method of claim 1 which comprises treating the subject over a period of at least 6 months.
24. The method of claim 23 , which comprises treating the subject over a period of at least 15 months.
25. The method of claim 1 , wherein the formulation is presented in a single prefilled syringe (PFS).
26. The method of claim 25 , wherein the volume in the prefilled syringe is between 0.1 mL and 0.8 mL.
27. The method of claim 1 , wherein the administration is subcutaneous into the abdomen.
28. The method of claim 1 , wherein the administration is subcutaneous into the upper arm.
29. The method of claim 1 , wherein the formulation is excisable following administration into the subject.
30. A pharmaceutical formulation comprising 1 mL or less of:
a) risperidone, or a pharmaceutically acceptable salt thereof, at a concentration of about 250-400 mg/mL, equivalent to risperidone;
b) a biodegradable triblock copolymer having the formula:
poly(lactic acid) v -poly(ethylene glycol) w ,-poly(lactic acid) x
wherein v and x are the number of repeat units ranging from 24 to 682 and w is the number of repeat units ranging from 4 to 273 and v=x or v≠x;
c) a biodegradable diblock copolymer having the formula:
methoxy poly(ethylene glycol) y -poly(lactic acid) z ,
wherein y and z are the number of repeat units, wherein y is the number of repeat units ranging from 3 to 45 and z is the number of units ranging from 7 to 327; and wherein the ratio of the biodegradable triblock copolymer of (b) and the biodegradable diblock copolymer of (c) is 1:3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19, in said formulation, which is insoluble in an aqueous environment,
for use in treating a psychiatric disease or disorder.