FIELD OF THE INVENTION
The present invention relates to the O-desmethylvenlafaxine palmitate salt in the solid form, including amorphous and crystaliine form of (±)-O-desmethylvenlafaxine palmitate and process for preparing the same thereof.
BACK GROUND AND PRIOR ART OF THE INVENTION
O-desmethyl venlafaxine (chemically known as 1-[2-(dimethylamino)-1-(4-phenol)ethyl]cyclohexanol) is a major metabolite of venlafaxine and has been shown to inhibit norepinephrine and serotonin uptake in the U.S. Pat. No. 4,535,186. O-desmethyl venlafaxine has the chemical structure as depicted herein below:

Salt formation provides a means of altering the physiochemical and resultant biological characteristics of a drug without modifying its chemical structure. Selection of a salt for a compound is an unpredictabee exercise that would require a pharmacist to engage in experimentation to determine which salt would be in fact suitable among the group of pharmaceutically acceptable salts. Stability, solubility and quantity of the crystalline struc!ure determine the selection of a particular salt. This is advantageous in dosage form developmen..
The invention of finding out novel solid forms of such salts, including amorphous forms and crystal forms of pharmaceutically useful compound provides a new opportuntty to improve the performanee characteristic of the final pharmaceutical produc.. It adds value to the material that a formulation scientist can use the same for designing, for example a pharmaceutical dosage form of a drug with targeted release profile or other desired characteristic.

The product patent US patent No. 4,535,186 describe the preparation of venlafaxine hydrochloride in almost all the examples and the preparation of venlafaxine fumarate in example-26. Further this patent discloses different acid addition salts of 0-desmethylvenlafaxine such as hydrochloric, hydrobromic, fumaric, maleic, succinic, sulfuric, phosphoric, tartaric, acetic, citric, oxalic and similar acids in Column 2, lines 35 to 42. The O-desmethyl venlafaxine formate addition salt is disclosed in the US patent No. 7,001,920. Aspartate and saccharinate are the other acid addition salts of 0-desmethyl venlafaxine disclosed in CN 101074200 and WO 2009017813 respectively.
SUMMARY OF THE INVENTION
The primary objective of the present invention is to provide O-desmethylvenlafaxine palmjtate salt in the solid form, including amorphous and crystalline form of (±)-O-desmethylvenlafaxine palmitate and process for preparing the same thereof.
It is an aspect of the invention to provide a crystalline form of O-desmethylvenlafaxine palmitate salt.
Further aspect of the present invention is to provide a process for the preparation of 0-desmethylvenlafaxine palmitate salt comprising the steps of treating 0-desmethylvenlafaxine with palmitic acid.
BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS
Figure 1: Powder X-ray diffraction of crystalline O-desmethylvenlafaxine palmitate
Figure 2: Differential Scanning Calorimetry of crystalline O-desmethylvenlafaxine
palmitate
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to the novel salt of O-desmethylvenlafaxine, particularly 0-desmethylvenlafaxine palmitate. Palmitate salts of O-desmethylvenlafaxine exist as

enantiomess and this invention includes racemic mixture as well as stereoisomerically pure forms of the same.
Stereoisomerically pure refers to the compound,, which are comprised of a greater proportion of the desired isomer than of the .optical antipode. A stereoisomerically pure compound is generally made up of at least 90% of the desired isomer based upon 100% total weight of O-desmethylvenlafaxine palmitate.
Peak locations and intensity for the XRPD pattern in Figure-1 are provided in table-1 below.
The peaks (expressed in 2e ± 0.20 2e) at 3.52, 3.69, 13.07, 13.17, 20.44 and 20.63 are characteristic of a crystaliine O-demethyvvenlafaxine palmitate. The DSC shows the peak value at 104.7 °C and the onset value is on 104.34 °C.

Palmitate salts of O-desmethylvenlafaxine may be formed by reacting palmitic acid with O-desmethylvenlafaxine free base in a suitable solvent or a mixture thereof.
The crystalline form of desmethylvanlafaxine could be converted to the amorphous form by the procedures known in the art e.g. spray drying, solvent precipitation, freeze drying etc.
Said suitable solvent is selected from. the group comprising of water, esters, ketones, phenols, alcohols, ethers, aromatic hydrocarbon,, amides, sulfoxide,, hydrocarbon,, nitriles, halogenated hydrocarbon,, pyridines or a mixtures thereof.
The "esters" include, for example, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, ethyl formate and the like. The "ketones" include, for example, acetone, methyl ethyl ketone, methyl isopropyl ketone, methyl butyl ketone, methyl isobutyl ketone and the like. The "phenols" include, for example, anisole and the like. The "alcohols" include, for example, methano,, ethanol, I-propanol, 2-propano,, 1-butanol, 2-butano,, 2-methyl-1-propanol, pentano,, 3-methyl-1-butanol, 2-methoxyethanol, 2-ethoxyethanol, ethylene glycol and the like. The "ethers" include, for example, t-butyl methyl ether, diethyl ether, 1,1-diethoxypropane, 1,1-dimethoxypropane, 2,2-dimethoxypropane, isopropyl ether, tetrahydrofuran, methyltetrahydrofuran and the like. The "aromatic hydrocarbon"" include, for example, chlorobenzene, toluene, xylene, cumene and the like. The "amides" include, for example, formamide, N,N-dimethylacetamide, N,N-dimethylformamide, N-methylpyrrolidone and the like.The "sulfoxides" include, for example, dimethylsulfoxide and the like.The "hydrocarbon"-include, for example, propane, hexane, pertane, octane, isooctane and the like.The "nitriles" include, for example, acetonitrlle and the like. The "halogenated hydrocarbon"" include, for example, chloroform, dichloromethane, dichloroethene, trichloroethene and the like. The "pyridine"" include, for example, pyridine and the like.

A mixture of palmitic acid and O-desmethylvenlafaxine free base is dissolved in a suitable solvent or a mixture of solvents at temperatures ranging from about 40°C to about l00-C Thereafter, crystaliization may be achieved either by the step of cooling the solution or by the step of concentrating or by the step of adding an antisolvent or any combinaiions of these steps thereof in any order. Crystaliization may be also facilitated by seeding with O-desmethylvenlafaxine palmitate crystals.
Said anti-solvent is selected from the group comprising of water, esters, ketones, phenols, alcohols, ethers, aromatic hydrocarbons, amides, sulfoxide,, hydrocarbons, nitriles, halogenated hydrocarbon,, pyridines or a mixtures thereof.
The "esters" include, for example, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, ethyl formate and the like. The "ketones" include, for example, acetone, methyl ethyl ketone, methyl isopropyl ketone, methyl butyl ketone, methyl isobutyl ketone and the like. The "phenols" include, for example, anisole and the like. The "alcohols" include, for example, methano,, ethanol, I-propanol, 2-propano,, 1-butanol, 2-butano,, 2-methyl-1-propanol, pentano,, 3-methyl-l-butanol, 2-methoxyethanol, 2-ethoxyethanol, ethylene glycol and the like. The "ethers" include, for example, t-butyl methyl ether, diethyl ether, I,l-diethoxypropane, 1,I-dimethoxypropane, 2,2-dimethoxypropane, isopropyl ether, tetrahydrofuran, methyltetrahydrofuran and the like. The "aromatic hydrocarbon"" include, for example, chlorobenzene, toluene, xylene, cumene and the like. The "amides" include, for example, formamide, N,N-dimethylacetamide, N,N-dimethylforrnamide, N-methylpyrrolidone and the like.The "sulfoxides" include, for example, dimethyl sulfoxide and the like.The "hydrocarbon"-include, for example, propane, hexane, pentane, octane, isooctane and the like.The "nitriles" include, for example, acetonitrlle and the like. The "halogenated hydrocarbon"-include, for example, chloroform, dichloromethane, dichloroethene, trichloroethene and the like. The "pyridines" include, for example, pyridine and the like.
The following examples are provided (or purposes of illustraiion only and should not be understood as definition of the limits of the invention.

Example-1
Preparation of O-desmethyl venlafaxine palmitate
26 ml of methano,, 2 gms of O-desmethyl venlafaxine and 2.06 gms of palmitic acid were mixed by stirring at 20-25°C for 10 minutes. The stirred mixture was heated to 55-58T with stirring for 30 minutes. The reaction mixture was cooled to 20 -25oC and concentrated under vacuum at 40°C to get oily mass. The traces of methanol are removed by azeotropic distillaiion with 40 ml of n-hexane at 40°C. The resultant oily mass was mixed with 30 ml of n-hexane and then cooled to 0oC followed by stirring of the mixture for one hour at 0oC. The solid was filtered, washed with 10 ml of cold n-hexane (0-5oC) and dried at 40°C for 14-16 hours to afford O-desmethyl venlafaxine palmitate as white crystals (3.1 gm, 79%).
Example-2
Preparation of O-desmethyl venlafaxine palmitate
14 ml of ethano,, 2 gms of O-desmethyl venlafaxine and 2.0 gms of palmitic acid were mixed by stirring at 20-25TC for 10 minutes. The stirred mixture was heated to 75- 78°C with stirring for 30 minutes. The reaction mixture was cooled to 20 -25oC and concentrated under vacuum at 40°C to get oily mass. The traces of ethanol are removed by azeotropic distillaiion with 40 ml of cyclohexane at 40°C. The resultant oily mass was mixed with 30 ml of cyclohexane and then cooled to O°C followed by stirring of the mixture for one hour at O°C. The solid was filtered, washed with 10 ml of cold cyclohexane (O-5oc) and dried at 40°C for 14-16 hours to afford O-desmethyl venlafaxine palmitate as white crystals (2.5gm, 65 %)

We Claim:
1. O-desmethyl-venlafaxine palmitate in solid form.
2. O-desmethyl-venlafaxine palmitate as claimed in claim 1, wherein the said solid is prepared by process comprising the steps of:

(a) reacting O-desmethyl-venlafaxine with palmitic acid in a suitable solvent;
(b) adding a non-solvent to the reaction mixture formed in the step (a);
(c) isolating or recovering the O-desmethylvenlafaxine palmitate in a solid form and;
(d) optionally purifying or crystallizing the O-desmethylvenlafaxine palmitate.
3. A Crystaliine O-desmethyl-venlafaxine palmitate.
4. A crystaliine O-desmethyl-venlafaxine palmitate having characteristic XRPD
• peaks at 3.52, 3.69, 13.07, 13.17,20444 and 20.63 28 ± 0.2° 28.
5. A solid form of O-desmethyl-venlafaxine palmitate having DSC characterized with a peak value of 104.7 °C.
6. A solid form of O-desmethyl-venlafaxine palmitate having DSC characterized with an onset value of 104.34 °C.