FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention
"A NOVEL POLYMORPH OP ASENAPINE MALEATE"
Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17thFloor, Kesar Solitaire, Plot No.5 Sector-19, Sanpada, Navi Munibai Maharashtra, India. Pin Code: 400705
1. The following specification particularly describes the invention and the manner in which it is to be performed.

A NOVEL POLYMORPH OF ASENAPINE MALEATE
FIELD OF THE INVENTION:
The present invention relates to novel polymorph Form E of asenapine maleate, to process of their preparation, pharmaceutical composition comprising Form E of asenapine maleate and their use in the treatment of schizophrenia.
BACKGROUND OF THE INVENTION:
Asenapine maleate is a psychotropic agent that is available for sublingual administration. Asenapine belongs to the class dibenzo-oxepino pyrroles. The chemical designation is (3aRS, 12bRS)-5-Chloro-2-methyl 2, 3, 3a, 12b-tetrahydro-1Hdibenzo [2, 3: 6, 7] oxepino [4, 5-c] pyrrole {2Z)-2-butenedioate (1:1) and is known from U.S.Patent No. 4,145,434 and is represented by compound of structural formula I.

Funke et al (Arzneim.-Forsch./Drug Res. 40 (1999), 536-539) have described Physico-chemical properties of asenapine maleate. This known crystalline asenapine maleate (form H or monoclinic form) has a melting point of 14l-145°C and is typically comprised of crystalline particles over 100µm in size as observed in micrographs.
U.S.Patent No. 7,741,358 discloses asenapine maleate form L or orthorhombic form and amorphous asenapine maleate. The asenapine maleate form L or orthorhombic form has a

melting point in the range of 138-142°C and is prepared by crystallization of asenapine maleate by cooling from an ethanol/water mixture containing dissolved asenapine maleate.
U.S.Patent publication no. 2008/0090892 discloses a process for preparing amorphous asenapine maleate by freeze drying an aqueous solution of asenapine maleate.
The inventors of U.S.Patent No. 7,741,358 claim certain processing and therapeutic advantages of asenapine maleate form L or orthorhombic form over asenapine maleate form H or monoclinic form, advantages may yet be realized by other heretofore undiscovered forms of asenapine maleate.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide novel polymorph Form E of asenapine maleate.
A second aspect of the present invention is to provide a process for preparing novel polymorph Form E of asenapine maleate comprising the steps of:
a. providing a solution of asenapine maleate in an alcohol solvent;
b. stirring the solution obtained in step a and
c. isolating novel polymorph Form E of asenapine maleate.
A third aspect of the present invention is to provide a pharmaceutical composition comprising novel polymorph Form E of asenapine maleate in association with one or more pharmaceutical!)' acceptable additives or excipients.
A fourth aspect of the present invention is to provide a method of treatment of schizophrenia comprising administering a therapeutically effective amount of a composition containing novel polymorph Form E of asenapine maleate in association with one or more pharmaceutical^ acceptable additives or excipients.

DETAIL DESCRIPTION OF THE INVENTION:
Asenapine may be obtained by following the prior-art methods such as those described in U.S.Patent No. 7,750,167 and U.S.Patent Publication nos 2008/0214832 and 2009/0227803.
A novel polymorph Form E of asenapine maleate may be characterized by XRPD pattern as depicted in figure 1.
A novel polymorph Form E of asenapine maleate may be characterized by data selected from a group comprising of: powder XRPD pattern having peaks at 9.7, 10.7, 16.1, 16.7, 16.9, 17.7, 18.5, 18.9, 19.2, 20.5, 20.9, 21.4, 22.4, 24.8, 25.2, 25.7, 26.8 ± 0.2 degrees two-theta.

Pos. [°2Th.] Height [cts] Area [cts*°2Th.] FWHM
[°2Th.] d-spacins
[A] Rel. Int. [%]
9.7042 361.57 49.17 0.1020 9.10688 24.07
10.7883 595.80 81.03 0.1020 8.19406 39.66
12.2326 205.84 44.79 0.1632 7.22968 13.70
12.4628 186.27 30.40 0.1224 7.09666 12.40
14.8834 55.43 18.09 0.2448 5.94748 3.69
15.5731 247.75 53.91 0.1632 5.68558 16.49
16.1639 429.78 187.04 0.3264 5.47907 28.61
16.7319 447.43 121.70 0.2040 5.29433 29.78
16.9237 515.37 84.11 0.1224 5.23476 34.30
17.7642 628.44 170.93 0.2040 4.98892 41.83
18.5451 1076.44 263.51 0.1836 4.78057 71.65
18.9067 1243.40 270.56 0.1632 4.68996 82.76
19.2371 349.70 76.09 0.1632 4.61014 23.28

19.9863 88.84 24.16 0.2040 4.43899 5.91
20.5767 342.28 93.10 0.2040 4.31293 22.78
20.9773 742.62 60.60 0.0612 4.23146 49.43
21.4980 1502.38 367.78 0.1836 4.13014 100.00
22.4099 1456.50 356.55 0.1836 3.96410 96.95
22.7966 277.32 75.43 0.2040 3.89772 18.46
23.6436 269.49 102.62 0.2856 3.75997 17.94
24.1162 156.72 25.58 0.1224 3.68734 10.43
24.8196 366.36 79.72 0.1632 3.58441 24.39
25.2693 558.63 91.17 0.1224 3.52164 37.18
25.7312 1447.05 432.96 0.2244 3.45945 96.32
26.8439 670.18 182.29 0.2040 3.31853 44.61
27.2510 276.48 45.12 0.1224 3.26987 18.40
28.9332 166.79 27.22 0.1224 3.08347 11.10
30.1136 195.27 84.98 0.3264 2.96524 13.00
30.8926 185.90 60.68 0.2448 2.89222 12.37
32.0959 103.73 33.86 0.2448 2.78648 6.90
32.7246 115.16 50.12 0.3264 2.73437 7.66
34.0553 81.50 26.60 0.2448 2.63051 5.42
34.4637 103.91 33.92 0.2448 2.60026 6.92
35.2608 89.39 14.59 0.1224 2.54329 5.95
35.9081 37.57 24.52 0.4896 2.49891 2.50
36.4837 55.81 18.22 0.2448 2.46079 3.72
37.0337 93.16 30.41 0.2448 2.42550 6.20

39.1503 83.36 27.21 0.2448 2.29911 5.55
A novel polymorph Form E of asenapine maleate may be characterized by melting point in the range of 110°C to 116°C.
A solution of asenapine maleate may be formed by reacting asenapine base with maleic acid in an alcoholic solvent at a temperature in the range of 40°C to 70°C.
Examples of alcoholic solvent may include methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, pentanol or mixture(s) thereof.
A solution of asenapine maleate in an alcoholic solvent may be stirred for at least 12 hours at a temperature in the range of-8°C to -10°C.
A novel polymorph Form E of asenapine maleate may be isolated by the steps of filtration, centrifugation, washing, drying and combination thereof.
A novel polymorph Form E of asenapine maleate may be washed with chilled (-5°C to 0°C) alcohol.
A novel polymorph Form E of asenapine maleate may be dried at a temperature in the range of 40°C to 60°C for 6 hours to 14 hours under reduced pressure.
The pharmaceutical composition comprising novel polymorph Form E of asenapine maleate may be in the form of sublingual tablet containing 5-mg or 10-mg asenapine; inactive ingredients include gelatin and mannitol.

BRIEF DESCRIPTION OF THE FIGURE:
Figure 1 depicts XRPD pattern for the novel polymorph Form E of asenapine maleate
XRD diffraction measurement was performed on X-Ray powder diffractometer Bruker D8
Advance powder diffractometer with the detector Lynxeye (Bruker). The analysis conditions
were as follows:
Scan range [°2-theta]: 2-39.9854;
Scan mode: continuous;
Step size [°2-theta]: 0.0170°;
Scan step time[s]: 51.0404 seconds;
Sample spin: 15 rpm;
Sample holder: glass;
PSD Length [°2Th]: 2.12
Irradiated Length [mm]: 10.00
Specimen Length [mm]: 10.00
Measurement Temperature [°C]: 25
Anode Material: Cu
K-Alpha[A]: 1.54060
Generator Settings: 40 mA, 45 kV
Goniometer Radius [mm]: 240
Dist. Focus-Diverg.Slit [mm]: 100.00
Prior to analysis, the samples were gently ground by means of mortar and pestle in order to obtain a fine powder. The sample might be mixed with n-dodecane in order to avoid the environment contamination by airborne particles coming from the powder. The ground sample or its suspension with n-dodecane was adjusted into a cavity of the sample holder and the surface of the sample was smoothed by means of a cover glass.

EXAMPLE:
In the following example, the preferred embodiments of the present invention are described only by way of illustrating the process of the invention. However, these are not intended to limit the scope of the present invention in any way.
Example 1: Preparation of novel polymorph Form E of asenapine maleate
A solution of asenapine (27gm) in ethanol (81ml) was added charcoal (2.7gm) and resulting reaction mixture was stirred for 30 minutes at 60°C to 65°C and then the resulting solution was filtered through hyflow-bed, hyflow-bed was washed with ethanol (69ml) and resulting clear filtrate was added a solution of maleic acid (12.2gm) in ethanol (25ml) at 60°C and then it was stirred for 30 minutes at 60°C to 65°C. The resulting solution was cooled to -10°C and then it was stirred 12 hours at -8°C to -10°C. The resulting solids were filtered, washed with chilled ethanol (14ml) and dried at 50°C for 12 hours to get title compound. Yield: 25gm
Purity: 99.89% (By HPLC) XRD: As depicted in Figure 1

WE CLAIM:
1. A compound which is novel polymorph Form E of asenapine maleate having substantially the same XRPD pattern as shown in Figure 1.
2. The compound of claim no. 1, having XRPD pattern comprising the peaks at 9.7, 10.7, 16.1, 16.7, 16.9, 17.7, 18.5, 18.9, 19.2, 20.5, 20.9, 21.4, 22.4, 24.8, 25.2, 25.7, 26.8 ± 0.2 degrees two-theta.
3. The compound of claim no. 1, is characterized by melting point in the range of 110°C to 116°C.
4. A process preparing novel polymorph Form E of asenapine maleate comprising the steps of:
a. providing a solution of asenapine maleate in an alcohol solvent;
b. stirring the solution obtained in step a and
c. isolating novel polymorph Form E of asenapine maleate.
5. The process according to claim no. 4, wherein solution of asenapine maleate is formed by reacting asenapine base with maleic acid in an alcoholic solvent at a temperature in the range of 40°C to 70°C.
6. The process according to claim nos. 4 and 5. wherein alcoholic solvent is selected from the group comprising of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, pentanol or mixture(s) thereof.
7. The process according to claim no. 4, wherein, solution of asenapine maleate in an alcoholic solvent is stirred for at least 12 hours at a temperature in the range of-8°C to -10°C.

8. The process according to claim no. 4, wherein novel polymorph Form E of asenapine maleate is isolated by the steps of filtration, centrifugation, washing with chilled alcohol (-5°C to 0°C), drying at a temperature in the range of 40°C to 60°C for 6 hours to 14 hours under reduced pressure.
9. A pharmaceutical composition comprising novel polymorph Form E of asenapine maleate in association with one or more pharmaceutically acceptable additives or excipients.
10. A method of treatment of schizophrenia comprising administering a therapeutically effective amount of a composition containing novel polymorph Form E of asenapine maleate in association with one or more pharmaceutically acceptable additives or excipients.