Pharmaceutical compositions having improved storage stability
The present invention relates to a pharmaceutical composition that provides long-term stability of a hydrolytically labile antipsychotic agent
1. A pharmaceutical composition comprising:
(a) Compound 1
(b) a non-ionic water insoluble and/or immiscible ester co-surfactant that is a sorbitan ester of a carboxylic acid, wherein the carboxylic acid comprises 4-20 carbon atoms;
(c) a water miscible and/or soluble non-ionic surfactant; and
(d) an aqueous vehicle;
wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product of Compound 1.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises less than 30 parts per million of the hydrolysis product of Compound 1 after standing for at least 24 months.
3. The pharmaceutical composition of claim 1 , wherein the water miscible and/or soluble non-ionic surfactant is a polyoxyethylene derivative of a sorbitan ester of a carboxylic acid, wherein the carboxylic acid comprises 8-14 carbon atoms.
4. The pharmaceutical composition of claim 1 , wherein the sorbitan ester is sorbitan laurate.
5. The pharmaceutical composition of claim 3 , wherein the polyoxyethylene derivative of a sorbitan ester is polysorbate 20.
6. A pharmaceutical composition comprising:
(a) 20-30 weight percent compound I:
(b) about 0.2-1 weight percent sorbitan laurate;
(c) about 0.1-0.3 weight percent polysorbate 20; and
(d) an aqueous vehicle;
wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product of Compound 1.
7. A method of treating schizophrenia in a subject in need thereof comprising administering to the subject the composition of claim 1 .
8. A method of treating schizophrenia in a subject in need thereof comprising administering to the subject the composition of claim 6 .
9. A method of treating bipolar disorder in a subject in need thereof comprising administering to the subject the composition of claim 6 .
10. A method of treating anxiety in a subject in need thereof comprising administering to the subject the composition of claim 6 .
11. A method of treating depression in a subject in need thereof comprising administering to the subject the composition of claim 6 .
12. A method of treating autism-related irritability in a subject in need thereof comprising administering to the subject the composition of claim 6 .
13. A method of treating acute mania in a subject in need thereof comprising administering to the subject the composition of claim 6 .
14. The pharmaceutical composition of claim 1 , wherein the hydrolysis product of Compound 1 is:
15. The pharmaceutical composition of claim 6 , wherein the hydrolysis product of Compound 1 is: