Pharmaceutical compositions comprising sorbitan esters

• US 9,034,867 B2
• Filed: 03/19/2012
• Issued: 05/19/2015
• Est. Priority Date: 03/18/2011
• Status: Active Grant

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Perry, Jason M., Deaver, Daniel R., Vandiver, Jennifer, Hickey, Magall B., Remenar, Julius F.
• Primary Examiner(s): Justice, Gina
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US13/423,606
• Publication Number:
  US 20120238552A1
• Time in Patent Office: 1,156 Days
• Field of Search: 514/220, 514/253.07
• US Class Current: 514/220
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4965 Non-condensed pyrazines
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants

Abstract

The present invention relates to a pharmaceutical composition comprising sorbitan esters of carboxylic acids that are useful for the delivery of anti-psychotic drugs.

Claims

1. A pharmaceutical composition comprising:

(a) compound A-7;

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 μ

m, Dv[50];

10-30 μ

m, and Dv[90];

less than 65 μ

mM.

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.

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.

16. An injectable pharmaceutical composition comprising:

(a) compound A-7;

17. An injectable composition comprising:

(a) compound A-7;

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.

29. A pharmaceutical composition comprising:

(a) 24-30 weight percent compound A-7;