Field of the invention:
The present disclosure relates to a novel crystalline olanzapine pamoate form-l and process for its preparation.
Back ground:
Olanzapine pamoate is a typical antipsychotic drug which belongs to the thienobenzodiazepine class. Olanzapine pamoate is chemically known as 10H-thieno [2, 3-b] [1,5]benzodiazepine, 2-methyl-4-(4-methyl-1-piperazinyl)-,4,4'naphthalenecarboxylate](1:1) and structurally represented as below:
Olanzapine pamoate Olanzapine pamoate is marketed as olanzapine pamoate monohydrate under the brand name of ZYPREXA RELPREW®. It is indicated for the treatment of schizophrenia.
US 6169084 patent discloses various crystalline forms of olanzapine pamoate namely olanzapine pamoate monohydrate, olanzapine pamoate THF solvate, olanzapine pamoate dimethanolate and olanzapine pamoate acetone solvate. According to US '084 patent olanzapine pamoate is prepared by reacting olanzapine base with pamoic acid in tetrahydrofuran solvent, followed by crystallization in ethanol solvent to get olanzapine pamoate.
US 7932249 patent discloses crystalline olanzapine pamoate ehydrate and its preparation, wherein olanzapine base is treated with pamoic acid in a solvent to get solution, which is diluted with water to get olanzapine pamoate monohydrate, it is further suspended in a mixture of water and water miscible solvent to get olanzapine pamoate ehydrate.

WO 2011091142A2 application discloses Form-A, Form-B, Form-C, Form-D, Form-E, Form F, Form-J, Form-M, Form-R, Form-S and amorphous olanzapine pamoate and their preparation.
A considerable amount of work needs to be done on the polymorphic characterization of olanzapine pamoate to identify other forms that can be generated.
The present invention provides novel polymorphic form of olanzapine pamoate and process for its preparation. According to the present invention the novel crystalline polymorphic form-l is an anhydrous, stable and feasible in large scale production with high yield and purity.
Summary:
A first aspect of the disclosure relates to a novel crystalline olanzapine pamoate form-l.
Still another aspect relates to process for the preparation of crystalline olanzapine pamoate polymorphic form-l.
Yet another aspect relates to a process for the preparation of crystalline olanzapine pamoate form-l, comprising the steps of:
a) reacting olanzapine with pamoic acid in a solvent,
b) adding step (a) solution to an anti-solvent,
c) filtering to get wet solid,
d) suspending solid from step I in an alcohol solvent, and
e) isolating crystalline olanzapine pamoate form-l.
Brief description of the drawings:
Fig.1 depicts an X-ray powder diffraction pattern of crystalline olanzapine pamoate form-l.
Detailed description:
The present disclosure relates to a novel crystalline olanzapine pamoate form-l and process for the preparation of olanzapine pamoate polymorphic form-l.
One embodiment relates to a novel crystalline olanzapine pamoate form-l.
Another embodiment relates to a novel crystalline olanzapine pamoate form-l, is characterized by X-ray powder diffraction pattern as shown in figure 1 with peaks at 8.18, 9.56, 13.79, 16.46, 21.67 and 22.03± 0.2 two-theta values.

Yet another embodiment relates to a process for the preparation of crystalline olanzapine pamoate form-l, comprising the steps of:
a) reacting olanzapine with pamoic acid in a solvent,
b) adding step (a) solution to an anti-solvent,
c) filtering to get wet solid,
d) suspending solid from step I in an alcohol solvent, and
e) isolating crystalline olanzapine pamoate form-l.
The olanzapine base and pamoic acid is dissolved in a solvent, to get clear solution, which is added to anti-solvent at ambient temperature, the obtained solid is filtered to get olanzapine pamoate. It is suspended in alcohol solvent, followed by stirring to get form-l of olanzapine pamoate.
According to the present invention olanzapine is reacted with pamoic acid in a solvent selected from N-methyl pyrrolidine, dimethyl formamide and dimethyl sulfoxide.
According to the present invention anti-solvent is selected from methanol, ethanol, n-propanol, isopropanol and butanol.
According to the present invention alcohol solvent is selected from methanol, ethanol, n-propanol and isopropanol.
Powder x-ray diffraction (PXRD):
The PXRD measurements were carried out using PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of 6/6 configuration and X'Celerator detector. The Cu- anode X-ray tube is operated at 40kV and 30mA. The experiments were conducted over the 26 range of 2.0°-50.0°, 0.030° step size and 50 seconds step time.
The following examples are provided for illustrative purposes only and are not intended to limit the scope of the invention in any way.
Examples:
Example-1: Preparation of olanzapine pamoate form-l.
Olanzapine (100gm) and Pamoic acid (125gm) were dissolved in dimethylsulfoxide (DMSO) (500ml) at 25-35°C. The resulted solution was stirred for 30minutes at 25-35°C. The reaction mass was added to isopropyl alcohol (3000ml) and maintained stirring for 1 hr at 25-35°C. The obtained solid was filtered to get wet cake. This wet cake was taken in ethanol (600ml) at 25-

35°C and stirred the mixture at 50-60°C for 1 hour. The mixture was cooled to 25-35°C and filtered the material, dried the material for 6hours at 50°C. Dry weight: 160gms

We Claim:
1. Crystalline olanzapine pamoate form-l.
2. Olanzapine pamoate form-l, which is characterized by X-ray powder diffraction pattern as shown in figure 1 with peaks at 8.18, 9.56, 13.79, 16.46, 21.67 and 22.03± 0.2 two-theta values.
3. A process for the preparation of crystalline olanzapine pamoate form-l, comprising the steps of:

a) reacting olanzapine with pamoic acid in a solvent,
b) adding step (a) solution to an anti-solvent,
c) filtering to get wet solid,
d) suspending solid from step I in an alcohol solvent, and
e) isolating crystalline olanzapine pamoate form-l.

4. The process according to claim 3, wherein solvent is selected from N-methyl pyrrolidine, dimethyl formamide and dimethyl sulfoxide.
5. The process according to claim 3, wherein anti-solvent is selected from methanol, ethanol, n-propanol, isopropanol and butanol.
6. The process according to claim 3, wherein alcohol solvent is selected from methanol, ethanol, n-propanol, isopropanol and butanol.