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 method for minimizing degradation of a hydrolytically labile antipsychotic agent comprising adding to a composition comprising the antipsychotic agent and an aqueous vehicle (a) a non-ionic water insoluble and/or immiscible ester co-surfactant and (b) a water miscible and/or soluble non-ionic surfactant, wherein the antipsychotic agent is Compound 1:
the non-ionic water insoluble and/or immiscible ester co-surfactant is sorbitan laurate;
the water miscible and/or soluble non-ionic surfactant is polysorbate 20; and
sorbitan laurate is provided in an amount sufficient to minimize the degradation of the antipsychotic agent.
2. The method of claim 1 , wherein the amount of sorbitan laurate sufficient to minimize degradation is 0.25-0.45 weight percent of the total composition.
3. The method of claim 1 , wherein the amount of sorbitan laurate sufficient to minimize degradation is 0.3-0.4 weight percent of the total composition.
4. A method for the preparation of an aqueous pharmaceutical composition comprising:
(a) 24-30 weight percent Compound 1:
(b) 0.3-0.4 weight percent sorbitan laurate;
(c) 0.1-0.3 weight percent polysorbate 20; and
(d) an aqueous vehicle
wherein the method comprises adding to the composition comprising Compound 1 and an aqueous vehicle (a) a stabilizing amount of sorbitan laurate and (b) polysorbate 20;
wherein the composition comprises less than 50 parts per million of the hydrolysis product of Compound 1.
5. The method of claim 4 , wherein the composition is in a ready to use form.
6. The method of claim 4 , wherein hydrolysis product is one of the following compounds:
7. A method for treating disorders of the central nervous system, comprising administering an effective amount of a composition formed by the method of claim 4 to an individual in need of such treatment.
8. The method of claim 7 , wherein the pharmaceutical composition comprises:
(a) about 26.6 weight percent Compound 1:
(b) about 0.37 weight percent sorbitan laurate;
(c) about 0.15 weight percent polysorbate 20; and
(d) an aqueous vehicle.
9. The method of claim 1 , wherein 0.3-0.4 weight percent sorbitan laurate and 0.1-0.3 weight percent polysorbate 20 are added to the composition, and wherein the composition comprises 24-30 weight percent Compound 1:
and
an aqueous vehicle.
10. The method of claim 1 , wherein about 0.37 weight percent sorbitan laurate and about 0.15 weight percent polysorbate 20 are added to the composition, and wherein the composition comprises about 26.6 weight percent Compound 1:
and
an aqueous vehicle.
11. The method of claim 6 , wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product after standing for at least 12 months.
12. The method of claim 6 , wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product after standing for at least 24 months.
13. The method of claim 6 , wherein the pharmaceutical composition comprises less than 30 parts per million of the hydrolysis product.
14. The method of claim 11 , wherein the pharmaceutical composition comprises less than 30 parts per million of the hydrolysis product after standing for at least 24 months.
15. The method of claim 12 , wherein the pharmaceutical composition comprises less than 24 parts per million of the hydrolysis product after standing for at least 24 months.
16. The method of claim 8 , wherein the pharmaceutical composition is administered as a single, undivided dose.
17. The method of claim 8 , wherein the disorder of the central nervous system is schizophrenia.
18. The method of claim 8 , wherein the disorder of the central nervous system is bipolar disorder.
19. The method of claim 8 , wherein the disorder of the central nervous system is depression.