Pharmaceutical compositions comprising sorbitan esters

1. A pharmaceutical composition comprising:

(a) compound of Formula (III) or (IV):

 wherein

R 3 is—CH 2 OC(O)R 1 , —CH 2 OC(O)OR 1 , —CH 2 OC(O)N(R 1 ) 2 or —C(O)R 1 ;

R 4 is—CH 2 OC(O)R 1 , —CH 2 OC(O)OR 1 , —CH 2 OC(O)N(R 1 ) 2 or —C(O)R 1 ;

wherein each R 1 is independently selected from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted aryl; and

wherein Y ⊖ is a pharmaceutically acceptable counterion;

(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]: 2-10μm, Dv[50]: 10-30μm, and Dv[90]: less than 65μmM.

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 of formula III or IV.

15. The composition of claim 1 , comprising approximately 20-30 weight percent compound of formula III or IV.

16. An injectable pharmaceutical composition comprising:

(a) a compound of formula III or IV:

 wherein

R 3 is—CH 2 OC(O)R 1 , —CH 2 OC(O)OR 1 , —CH 2 OC(O)N(R 1 ) 2 or —C(O)R 1 ;

R 4 is—CH 2 OC(O)R 1 , —CH 2 OC(O)OR 1 , —CH 2 OC(O)N(R 1 ) 2 or —C(O)R 1 ;

wherein each R 1 is independently selected from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted aryl; and

wherein Y ⊖ is a pharmaceutically acceptable counterion; 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) a compound of formula III or IV:

 wherein

R 3 is—CH 2 OC(O)R 1 , —CH 2 OC(O)OR 1 , —CH 2 OC(O)N(R 1 ) 2 or —C(O)R 1 ;

R 4 is—CH 2 OC(O)R 1 , —CH 2 OC(O)OR 1 , —CH 2 OC(O)N(R 1 ) 2 or —C(O)R 1 ;

wherein each R 1 is independently selected from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted aryl; and

wherein Y ⊖ is a pharmaceutically acceptable counterion;

(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. 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.

20. The method of claim 19 , wherein the disorder is selected from the group consisting of anxiety, depression, bipolar disorder, autism-related irritability, and a psychotic condition.