DESC:Aspects of the present application relates to formic acid salt of evocalcet and process for the preparation thereof.
Evocalcet is useful for the prevention or treatment of diseases such as hyperparathyroidism. The chemical name of evocalcet is 2- {4-[(3 S ) -3- {[(1 R ) -1- (Naphthalen-1-yl) ethyl] amino} pyrrolidin-1-yl] phenyl} acetic acid, the structural formula is shown below.

US8362274B2 describes evocalcet and its pharmaceutical composition. US9643920B2 describes two crystalline forms of evocalcet (Form A and Form B) and process for the preparation thereof.
The physicochemical properties of a solid form is a critical parameter in the development of pharmaceutical dosage forms and these properties can affect the bioavailability, stability and processability of the active pharmaceutical ingredient. It is known that a solid active pharmaceutical ingredient can exist in amorphous and crystalline state. Crystalline solids may further exist as various polymorphs and solvates.
The discovery of new polymorphs and solvates of a pharmaceutical active compound provides an opportunity to improve the performance of a drug product in terms of its bioavailability or release profile in vivo, or it may have improved stability or advantageous handling properties. Polymorphism is an unpredictable property of any given compound. This subject has been reviewed in articles, including A. Goho, "Tricky Business," Science News, August 21, 2004. In general, one cannot predict whether there will be more than one form for a compound, how many forms will eventually be discovered, or how to prepare any previously unidentified form.
The discovery of new forms of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, storage stability, and ease of purification. Accordingly, the present inventors have found novel formic acid salt of evocalcet with enhanced storage stability, solubility and processability.

SUMMARY OF THE INVENTION
In an aspect, the present application provides a formic acid salt of evocalcet.
In an aspect, the present application provides a formic acid salt of evocalcet (DRL1), characterized by a PXRD pattern comprising the peaks at about 7.2, 13.1, 23.4 ± 0.2° 2?.
In an aspect, the present application provides a formic acid salt of evocalcet (DRL2), characterized by a PXRD pattern comprising the peaks at about 7.6, 11.4, 13.1 and 16.9 ± 0.2° 2?.
In another aspect, the present application provides a process for the preparation of formic acid salt of evocalcet comprising the steps of:
a) dissolving evocalcet in formic acid;
b) adding the solution obtained in step a) to anti solvent;
c) isolating the formic acid salt of evocalcet;
d) optionally drying the solid material obtained in step c)
In another aspect, the present application provides a pharmaceutical composition comprising formic acid salt of evocalcet with at least one pharmaceutically acceptable excipient.

BRIEF DESCRIPTION OF THE DRAWING
Figure 1 is an illustrative powder X-ray diffraction pattern of formic acid salt of evocalcet (DRL1) prepared by the method of Example No 1.
Figure 2 is an illustrative powder X-ray diffraction pattern of formic acid salt of evocalcet (DRL2) prepared by the method of Example No 2.

DETAILED DESCRIPTION OF THE INVENTION
In an aspect, the present application provides a formic acid salt of evocalcet.
In an aspect, the present application provides a formic acid salt of evocalcet (DRL1), characterized by a PXRD pattern comprising the peak at about 7.2, 13.1, 23.4 ± 0.2° 2?.
In an embodiment, the application provides formic acid salt of evocalcet (DRL1), characterized by a PXRD pattern having one or more additional peaks at about 15.2, 16.7 and 25.9±0.2° 2?.
In an embodiment, the application provides formic acid salt of evocalcet (DRL1), characterized by a PXRD pattern of figure 1.
In an aspect, the present application provides a formic acid salt of evocalcet (DRL2), characterized by a PXRD pattern comprising the peak at about 7.6, 11.4, 13.1 and 16.9 ± 0.2° 2?.
In an embodiment, the application provides formic acid salt of evocalcet (DRL2), characterized by a PXRD pattern having one or more additional peaks at about 8.8,13.7,15.2 and 22.9±0.2° 2?.
In an embodiment, the application provides formic acid salt of evocalcet (DRL2), characterized by a PXRD pattern of figure 2.
In another aspect, the present application provides a process for the preparation of formic acid salt of evocalcet comprising the steps of:
a) dissolving evocalcet in formic acid;
b) adding the solution obtained in step a) to anti solvent;
c) isolating the formic acid salt of evocalcet;
d) optionally drying the solid material obtained in step c)
In an embodiment, step a) may be carried out by dissolving evocalcet in formic acid. Alternatively, the solution may be provided by taking the reaction mixture containing evocalcet in formic acid.
In an embodiment of step a), the evocalcet may be dissolved in formic acid by heating the reaction mixture to obtain a homogenous solution. The solution may be filtered to make it particle free.
In embodiments of step b), adding the solution obtained in step a) to anti-solvent selected from water, methyl tert-butyl ether (MTBE), toluene, heptane, or mixtures thereof.
In embodiment of step b), the isolation may be effected by combining the solution of step a) with a suitable anti-solvent. Adding the solution obtained in step a) to the anti-solvent, or adding an anti-solvent to the solution obtained in step a), to effect the crystallization process are both within the scope of the present invention. After combining with anti-solvent, the reaction mass may be maintained from 15 minutes to 15 hours or longer.
In an embodiment of step c), the isolation of formic acid salt of evocalcet may be carried out by any methods known in the art or procedures described in the present application. In an embodiment, formic acid salt of evocalcet may be isolated by employing any of the techniques, but not limited to: filtration by gravity or suction, decantation, centrifugation, or other techniques specific to the equipment used and the like, and optionally washing with a solvent.
In an embodiment of step d), drying formic acid salt of evocalcet may be carried out at temperatures and times sufficient to achieve desired quality of product. Drying may be carried out at about 30°C or above at which formic acid salt of evocalcet is stable and for any time period required for obtaining a desired quality, such as from about 15 minutes to 10 hours or longer.
In another aspect, the present application provides formic acid salt of evocalcet is stable at elevated temperatures for an extended period of time.
Starting materials used for the preparation of formic acid salt of evocalcet according to any of the aspects of the present application may be any crystalline or amorphous in nature. Further, these starting materials may be purified according to any of the method known in the art such as recrystallization, slurrying, acidbase treatment i.e., salt making and breaking, chromatography, fractional distillation or any other separation methods, before using. Evocalcet that may be used as the input for the process of the present invention may be obtained by the processes described in the art. For example, evocalcet may be prepared by the processes described in US8362274B2 (or) US9643920B2.
In another aspect, the present application provides a pharmaceutical composition comprising formic acid salt of evocalcet and atleast one additional pharmaceutically acceptable excipient. Pharmaceutically acceptable excipients that are useful in the present application include, but are not limited to: diluents such as starches, pregelatinized starches, lactose, powdered celluloses, microcrystalline celluloses, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar, or the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methyl celluloses, pregelatinized starches, or the like; disintegrants such as starches, sodium starch glycolate, pregelatinized starches, crospovidones, croscarmellose sodium, colloidal silicon dioxide, or the like; lubricants such as stearic acid, magnesium stearate, zinc stearate, or the like; glidants such as colloidal silicon dioxide or the like; solubility or wetting enhancers such as anionic or cationic or neutral surfactants; complex forming agents such as various grades of cyclodextrins or resins; release rate controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl methylcelluloses, ethylcelluloses, methylcelluloses, various grades of methyl methacrylates, waxes, or the like.
In another aspect, the present application provides chemical purity of evocalcet may be more than 99% by HPLC or more than 99.5% by HPLC or more than 99.9% by HPLC.
In another aspect, the present application provides particle size (D90) of evocalcet may be less than 100 microns or less than 50 microns or less than 20 microns.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application.

Definition
The term "about" when used in the present application preceding a number and referring to it, is meant to designate any value which lies within the range of ±10%, preferably within a range of ±5%, more preferably within a range of ±2%, still more preferably within a range of ±1 % of its value. For example "about 10" should be construed as meaning within the range of 9 to 11, preferably within the range of 9.5 to 10.5, more preferably within the range of 9.8 to 10.2, and still more preferably within the range of 9.9 to 10.1.

Examples
Example-1: Preparation of formic acid salt of evocalcet (DRL1)
Evocalcet (500 mg) was dissolved in formic acid (2 ml) at 25°C. The obtained clear solution was added to water (30 ml) at 25°C. The reaction mixture was stirred for 45 hrs at 25°C. The resulted slurry was filtered under vacuum to obtain the title compound.

Example-2: Preparation of formic acid salt of evocalcet (DRL2)
Evocalcet (500 mg) was dissolved in formic acid (2 ml) at 25°C. The obtained clear solution was added to MTBE (30 ml) at 25°C. The reaction mixture was stirred for 1 hr 15 minutes at 25°C. The resulted slurry was filtered under vacuum and washed with MTBE (20 ml). The obtained solid material was dried for 24 hrs at 60°C to obtain the title compound.
,CLAIMS:1. A formic acid salt of evocalcet.
2. The formic acid salt of evocalcet (DRL1) as claimed in claim 1, characterized by a PXRD pattern comprising the peaks at about 7.2, 13.1, 23.4 ± 0.2° 2?.
3. The formic acid salt of evocalcet (DRL2) as claimed in claim 1, characterized by a PXRD pattern comprising the peaks at about 7.6, 11.4, 13.1 and 16.9 ± 0.2° 2?.
4. A process for the preparation of formic acid salt of evocalcet comprising the steps of:
a) dissolving evocalcet in formic acid;
b) adding the solution obtained in step a) to anti solvent;
c) isolating the formic acid salt of evocalcet;
d) optionally drying the solid material obtained in step c)
5. The process of formic acid salt of evocalcet as claimed in claim 4, wherein the anti-solvent is selected from water, methyl tert-butyl ether (MTBE), toluene, heptane, or mixtures thereof.
6. A pharmaceutical composition comprising formic acid salt of evocalcet with at least one pharmaceutically acceptable excipient.
7. The pharmaceutical composition of formic acid salt of evocalcet as claimed in claim 6, wherein the excipient is selected from microcrystalline celluloses, mannitol, sorbitol, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methyl celluloses, crospovidones, croscarmellose sodium, colloidal silicon dioxide, stearic acid, magnesium stearate, zinc stearate, colloidal silicon dioxide cyclodextrins or mixtures thereof.