Injectable formulations containing asenapine and method of treatment using same

1. A pharmaceutical formulation comprising an aqueous suspension of particulate, crystalline asenapine hemipamoate exhibiting XRPD diffraction peaks at °2-theta of 11.9, 16.5, 18.8, 19.4 and 23.4, wherein the asenapine hemipamoate is present in the formulation in a concentration in excess of at least about 10 mg/mL.

2. The formulation of claim 1 wherein the formulation comprises a phosphate buffer and asenapine is present in excess of at least about 100 mg/mL.

3. The formulation of claim 2 wherein the concentration of asenapine hemipamoate present is in excess of at least about 200 mg/mL.

4. The formulation of claim 3 wherein the particles of the suspended asenapine hemipamoate have a d 50 -value as measured by laser diffractometry of from about 3.5 microns to about 28 microns.

5. The formulation of claim 2 further including polyethylene glycol as a dispersing agent, and wherein said formulation has a pH of about 7.0.

6. A formulation comprising:

(i) from more than about 100 mg/mL to about 300 mg/mL of particles of crystalline Form II of asenapine hemipamoate which have not been classified and as defined by the XRPD diffraction peaks in Table I, wherein the particles have a laser diffractometry d 50 -value of from about 3.5 microns to about 28 microns;

(ii) water;

(iii) up to about 30 mg of polyethylene glycol/mL of water present; and

(iv) a buffer.

7. A pharmaceutical formulation comprising an aqueous suspension of particles of crystalline Form II of asenapine hemipamoate, as defined by the XRPD diffraction peaks in Table I, wherein:

(i) said particles have a laser diffractiometry d 50 -value of from about 3.5 microns to about 28 microns; and

(ii) the concentration of asenapine hemipamoate present in the formulation is at least sufficient so that when a depot of the formulation is administered to a patient by IM injection in a sufficient quantity to provide a therapeutically effective plasma concentration, the plasma concentration observed is not particle-size dependent.

8. The formulation of claim 6 wherein the concentration of asenapine hemipamoate is greater than at least about 100 mg/mL.

9. The formulation of claim 6 wherein said buffer was prepared by combining: disodium hydrogen phosphate in an amount of from about 1.0 mg/mL to about 1.2 mg/mL of water present; sodium dihydrogen phosphate in an amount of about 0.5 mg/mL of water present; sodium chloride in an amount of about 7.6 mg/mL of water present; and titrating the mixture with aliquots of sodium hydroxide and phosphoric acid until the mixture attains a pH of about 7.0.

10. A depot prepared by providing an IM injection of the formulation of claim 1 .

11. A depot of claim 10 which comprises a volume providing a therapeutically effective plasma concentration of asenapine for a period of either 2 weeks, 3 weeks, or 4 weeks.

12. A method of treating a CNS disease comprising administering a depot according to claim 10 to a patient.

13. The method of claim 12 wherein the disease treated is schizophrenia or a bipolar disorder.

14. An asenapine hemipamoate salt having an XRPD pattern which conforms to that of FIG. 3 b.

15. A formulation adapted for depot administration comprising an asenapine hemipamoate salt having an XRPD pattern which conforms to that of FIG. 3 b.

16. The formulation of claim 1 wherein said crystalline Form II of asenapine hemipamoate has an XRPD pattern which conforms to that of FIG. 3 b.