Pharmaceutical compositions comprising sorbitan esters
View Patent ↗The present invention relates to a pharmaceutical composition comprising sorbitan esters of carboxylic acids that are useful for the delivery of anti-psychotic drugs.
1. A pharmaceutical composition comprising:
(a) compound A-7:
(b) sorbitan laurate;
(c) polysorbate 20; and
(d) an aqueous vehicle
wherein the composition forms an aqueous, flocculated, injectable suspension.
2. The composition of claim 1 , wherein the composition comprises components (b) and (c) at a ratio that results in flocs comprising component (a), wherein the flocs settle to greater than a predetermined sediment bed height, such that components (a), (b) and (c) can be resuspended for injection.
3. The composition of claim 2 , wherein the bed height is comprised of at least a 20 to 80% increase in sediment height compared to a non flocculated composition after 24 hours of undisturbed sitting.
4. The composition of claim 2 , wherein components (a), (b) and (c) can be resuspended for injection within 1-60 seconds of handshaking.
5. The composition of claim 1 , wherein the ratio of components (b) to (c) is such that the composition can be injected using a 20 to 25 gauge needle.
6. The composition of claim 2 , wherein (a), (b), and (c) form flocs having the following sizes: Dv[10]: 2-10 μm, Dv[50]: 10-30 μm, and Dv[90]: less than 65 μmM.
7. The composition of claim 1 , wherein the ratio of components (b) to (c) is approximately 5 to 2, by weight.
8. The composition of claim 1 , comprising about 0.2-1 weight percent sorbitan laurate.
9. The composition of claim 1 , comprising about 0.4-0.7 weight percent sorbitan laurate.
10. The composition of claim 1 , comprising about 0.5 weight percent sorbitan laurate.
11. The composition of claim 1 , comprising about 0.05-0.8 weight percent polysorbate 20.
12. The composition of claim 1 , comprising about 0.1-0.3 weight percent polysorbate 20.
13. The composition of claim 1 , comprising about 0.2 weight percent polysorbate 20.
14. The composition of claim 1 , comprising approximately 15-35 weight percent compound A-7.
15. The composition of claim 1 , comprising approximately 20-30 weight percent compound A-7.
16. An injectable pharmaceutical composition comprising:
(a) compound A-7:
wherein component (a) is in a weight ratio of approximately 15-35%;
(b) sorbitan laurate in a weight ratio of approximately 0.2-1%
(c) polysorbate 20 in a weight ratio of approximately 0.05-0.8%; and
(d) an aqueous carrier.
17. An injectable composition comprising:
(a) compound A-7:
(b) sorbitan laurate;
(c) polysorbate 20; and
(d) an aqueous vehicle.
18. The composition of claim 17 , wherein the composition is formulated for modulating tissue reaction associated with the delivery of a water-insoluble antipsychotic agent.
19. The composition of claim 18 , wherein the modulation of the tissue reaction is a reduction in the irritation at the site of injection.
20. The composition of claim 17 , wherein the composition further comprises a buffer.
21. The composition of claim 20 , wherein the buffer is a phosphate, citrate, tartrate or acetate buffer.
22. A method for treating disorders of the central nervous system, comprising administering an effective amount of the composition of claim 1 to an individual in need of such treatment.
23. The method of claim 22 , wherein the disorder is anxiety or depression.
24. The method of claim 22 , wherein the disorder is bipolar disorder.
25. The method of claim 22 , wherein the disorder is autism-related irritability.
26. The method of claim 22 , wherein the disorder is a psychotic condition.
27. The method of claim 26 , wherein the psychotic condition is schizophrenia or schizophreniform diseases.
28. The method of claim 26 , wherein the psychotic condition is acute mania.
29. A pharmaceutical composition comprising:
(a) 24-30 weight percent compound A-7:
(b) 0.2-1 weight percent sorbitan laurate;
(c) 0.1-0.3 weight percent polysorbate 20; and
(d) an aqueous vehicle.