DESC:FIELD OF THE INVENTION:
The present invention relates to Tegoprazan Fendizoate of Formula-II and Tegoprazan Salicylate of Formula-IV.
The present invention also relates to an efficient and industrially advantageous process for the preparation of Tegoprazan Fendizoate of Formula-II and Tegoprazan Salicylate of Formula-IV.
BACKGROUND OF THE INVENTION:
Tegoprazan is chemically known as (-)-4-[((4S)-5,7-difluoro-3,4-dihydro-2H-chromen-4-yl)oxy]-N,N,2-trimethyl-1H-benzimidazole-6-carboxamide, having the structure of Formula-I.

[Formula-I]
Tegoprazan has been developed by RaQualia Pharma Inc. and in the partnership with CJ HealthCare Corporation launched in South Korea. Tegoprazan was approved by Korean Food and Drug Administration (KFDA) on July 05th, 2018 under the proprietary name K-CAP®. Tegoprazan is a pharmaceutical ingredient for preventing and treating diseases mediated by an acid pump antagonistic activity, including gastrointestinal diseases, for example, a gastroesophageal disease, a gastroesophageal reflux disease (GERD), a peptic ulcer, a gastric ulcer and a duodenal ulcer, an ulcer induced by NSAID, a gastritis, a Helicobacter pylori infection, a dyspepsia and a functional dyspepsia, a Zollinger-Ellison syndrome, a nonerosive reflux disease (NERD), a visceral pain, a purosis, a nausea, an esophagitis, a dysphagia, a salivation, an airway lesion and an asthma.
U.S. patent number US7723321 first discloses Tegoprazan. However, this patent does not disclose specific salt of Tegoprazan.
U.S. patent number US9908870 discloses crystalline Tegoprazan, which is advantageous for preparing a formulation because of being stable under a long-term and stress storage condition, having no crystal transition observed due to a change with the passage of time, having an excellent photostability, and having a low hygroscopicity and a low induction of static electricity.
The above-mentioned compound has a limitation to selection of salts because the compound has a very low water solubility (0.02 mg/ml, pH 6.8), has a solubility increased (0.7 mg/ml, pH 3.0) under an acidic condition, but without a great effect, and has a degradation product increased under an acidic condition, such that the compound does not have a good stability. Also, in case of using a solubilizing agent, such as a surfactant, to improve solubility, excessive amounts of excipients are needed, thus causing a difficulty.
U.S. patent number US11535610 specifically discloses several acid addition salts of Tegoprazan, wherein acid is selected from succinic acid, fumaric acid, oxalic acid, citric acid, L-pyroglutamic acid, 1,5-naphinalene disulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, L-malic acid, nicotinic acid, 2,5-dihydroxybenzoic acid and L-tartaric acid.
The above-mentioned salts are unstable except pidolate and malate salt of Tegoprazan. However, pidolate and malate salt are costly. Further, these salts are prepared using multiple solvents namely methanol, acetone and ethyl acetate. Therefore, not an attractive option for commercial scale production.
Most of the prior art salts have their own disadvantages like higher cost, use of multiple solvents and stability. Thus, there is an urgent need to develop novel form which solves problems of higher cost, multiple solvents and stability, which is suitable for large scale industrial production.
OBJECT OF THE INVENTION:
The main object of the present invention is to provide Tegoprazan Fendizoate of Formula-II.
Another object of the present invention is to provide a process for the preparation of Tegoprazan Fendizoate of Formula-II.
Another one object of the present invention is to provide Tegoprazan Salicylate of Formula-IV.
One more object of the present invention is to provide a process for the preparation of Tegoprazan Salicylate of Formula-IV.

SUMMARY OF INVENTION:
First aspect of the present invention is to provide a Tegoprazan Fendizoate of Formula-II,

[Formula-II]
Second aspect of the present invention is to provides a process for the preparation of Tegoprazan Fendizoate of Formula-II,

[Formula-II]
comprising reacting Tegoprazan of Formula-I,

[Formula-I]
with Fendizoic acid of Formula-III,

[Formula-III]
to obtain a Tegoprazan Fendizoate of Formula-II.
Third aspect of the present invention is to provide a Tegoprazan Salicylate of Formula-IV,

[Formula-IV]
Fourth aspect of the present invention is to provides a process for the preparation of Tegoprazan Salicylate of Formula-IV,

[Formula-IV]
comprising reacting Tegoprazan of Formula-I,

[Formula-I]
with Salicylic acid of Formula-V,

[Formula-V]
to obtain a Tegoprazan Salicylate of Formula-IV.

According to fifth embodiment, present invention is to provide a compound of Formula-VI,

[Formula-VI]
“Wherein R1 and R2 are selected from H or OH with proviso that at least one of R1 and R2 is H”

According to sixth embodiment, present invention is to provides a process for the preparation of compound of Formula-VI,

[Formula-VI]
“Wherein R1 and R2 are selected from H or OH with proviso that at least one of R1 and R2 is H”
comprising reacting Tegoprazan of Formula-I,

[Formula-I]
with 3-hydroxybenzoic acid or 4-hydroxy benzoic acid in presence of solvent.
BRIEF DESCRIPTION OF DRAWINGS:
Figure 01: Illustrates the X-ray powder diffractogram (XRPD) of Tegoprazan Fendizoate of Formula-II obtained according to example-01.
Figure 02: Illustrates the X-ray powder diffractogram (XRPD) of Tegoprazan Salicylate of Formula-IV obtained according to example-02.
DETAILED DESCRIPTION OF INVENTION:
In order to provide a clear and consistent understanding of the terms used in the present specification, a number of definitions are provided below. Moreover, unless defined otherwise, all technical and scientific terms as used herein have the same meaning as understood by the person skilled in the art.
The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may not only mean “one”, but also encompasses the meaning of “one or more”, “at least one”, and “one or more than one”. Similarly, the word “another” may mean at least a second or more.
As used in this specification, the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “consisting” (and any form of consisting, such as “consists”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “include” and “includes”) or “containing” (and any form of containing, such as “contain” and “contains”), are inclusive or open-ended and do not exclude additional, unrecited elements or process steps.
The invention will now be described in detail in connection with certain preferred embodiments, so that various aspects thereof may be fully understood and appreciated.
According to first embodiment, present invention is to provide a Tegoprazan Fendizoate of Formula-II,

[Formula-II].
According to second embodiment, present invention is to provides a process for the preparation of Tegoprazan Fendizoate of Formula-II,

[Formula-II]
comprising reacting Tegoprazan of Formula-I,

[Formula-I]
with Fendizoic acid of Formula-III,

[Formula-III]
to obtain a Tegoprazan Fendizoate of Formula-II.
Tegoprazan of Formula-I used as a starting material can be prepared by processes known in the prior-art or by method as described in IN202221060610.
In the second embodiment, Tegoprazan of Formula-I can be reacted with Fendizoic acid to obtain Tegoprazan Fendizoate of Formula-II.
In the second embodiment, Tegoprazan of Formula-I can be reacted with Fendizoic acid in presence of solvent.
The solvent can be selected from the group consisting of alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, secondary-butyl alcohol or tert-butyl alcohol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; polar aprotic solvent such as dimethylsulfoxide, N,N-dimethylformamide or N-methylpyrrolidone; water; or mixture(s) thereof.
In the second embodiment, Fendizoic acid can be used in 0.5 to 3.0 molar equivalent with respect to Tegoprazan of Formula-I.
In the second embodiment, solvent can be used in 2.0 volume to 15.0 volume with respect to Tegoprazan of Formula-I.
In the second embodiment, Tegoprazan of Formula-I can be reacted with Fendizoic acid at temperature of 10°C to reflux temperature of solvent used.
Tegoprazan Fendizoate of Formula-II can be isolated by removing the solvent followed by drying. Generally, solvent can be removed by distillation or filtration.
Resulting Tegoprazan Fendizoate of Formula-II may have purity of greater than 98%, preferably greater than 99.0% by HPLC (High-performance liquid chromatography).
Tegoprazan Fendizoate of Formula-II can also be isolated by known methods such as crystallization, recrystallization, or solvent-anti solvent methods.
The solvent can be selected from the group consisting of alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, secondary-butyl alcohol or tert-butyl alcohol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; polar aprotic solvent such as dimethylsulfoxide, N,N-dimethylformamide or N-methylpyrrolidone; water; or mixture(s) thereof.
Anti-solvent can be selected from the group consisting of ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; alkane such as n-hexane, heptane or cyclohexane or mixture(s) thereof.
Generally, Tegoprazan Fendizoate of Formula-II can be stirred in presence of solvent followed by heating the reaction mixture and anti-solvent can be added to resulting mixture. Resulting mixture can be cooled to precipitate the solid.
Resulting solid can be isolated by decantation or filtration followed by drying to obtain a Tegoprazan Fendizoate of Formula-II.
Resulting Tegoprazan Fendizoate of Formula-II may have purity of greater than 98%, preferably greater than 99.0% by HPLC (High-performance liquid chromatography).
Resulting Tegoprazan Fendizoate of Formula-II according to present invention is stable amorphous or crystalline in nature.
According to third embodiment, present invention is to provide a Tegoprazan Salicylate of Formula-IV,

[Formula-IV].
According to fourth embodiment, present invention is to provides a process for the preparation of Tegoprazan Salicylate of Formula-IV,

[Formula-IV]
comprising reacting Tegoprazan of Formula-I,

[Formula-I]
with Salicylic acid of Formula-V,

[Formula-V]
to obtain a Tegoprazan Salicylate of Formula-IV.
Tegoprazan of Formula-I used as a starting material can be prepared by processes known in the prior-art or by method as described in IN202221060610.
In the fourth embodiment, Tegoprazan of Formula-I can be reacted with Salicylic acid to obtain Tegoprazan Salicylate of Formula-IV.
In the fourth embodiment, Tegoprazan of Formula-I can be reacted with Salicylic acid in presence of solvent.
The solvent can be selected from the group consisting of alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, secondary-butyl alcohol or tert-butyl alcohol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; alkane such as n-hexane, n-heptane or cyclohexane or mixture(s) thereof.
In the fourth embodiment, Salicylic acid can be used in 0.5 to 3.0 molar equivalent with respect to Tegoprazan of Formula-I.
In the fourth embodiment, solvent can be used in 2.0 volume to 15.0 volume with respect to Tegoprazan of Formula-I.
In the fourth embodiment, Tegoprazan of Formula-I can be reacted with Salicylic acid at temperature of 10°C to reflux temperature of solvent.
Tegoprazan Salicylate of Formula-IV can be isolated by removing the solvent followed by drying. Generally, solvent can be removed by distillation or degassing.
Resulting Tegoprazan Salicylate of Formula-IV may have purity of greater than 98%, preferably greater than 99.0% by HPLC (High-performance liquid chromatography).
Tegoprazan Salicylate of Formula-IV can also be isolated by known methods such as crystallization, recrystallization, or solvent-anti solvent methods.
The solvent can be selected from the group consisting of alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, secondary-butyl alcohol or tert-butyl alcohol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; polar aprotic solvent such as dimethylsulfoxide, N,N-dimethylformamide or N-methylpyrrolidone; water; or mixture(s) thereof.
Anti-solvent can be selected from the group consisting of ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; alkane such as n-hexane, heptane or cyclohexane or mixture(s) thereof.
Tegoprazan Salicylate of Formula-IV can also be stirred in presence of solvent followed by heating the reaction mixture and anti-solvent can be added to resulting mixture. Resulting mixture can be cooled to precipitate the solid.
Resulting solid can be isolated by decantation or filtration followed by drying to obtain a Tegoprazan Salicylate of Formula-IV.
Resulting Tegoprazan Salicylate of Formula-IV may have purity of greater than 98%, preferably greater than 99.0% by HPLC (High-performance liquid chromatography).
Tegoprazan Salicylate of Formula-IV according to present invention is stable amorphous or crystalline in nature.
Amorphous Tegoprazan Salicylate of Formula-IV according to present invention is stable for 9 months at 25°C and 60% relative humidity (Rh).
Amorphous Tegoprazan Salicylate of Formula-IV according to present invention is stable for 9 months at 40°C and 75% relative humidity (Rh).
Amorphous Tegoprazan Salicylate of Formula-IV when stored for 9 months at 25°C/ 60%Rh or 40°C/ 75%Rh does not show any changes in HPLC for comparison.
Amorphous Tegoprazan Salicylate of Formula-IV is stable and does not degrades based on purity of HPLC.

According to fifth embodiment, present invention is to provide a compound of Formula-VI,

[Formula-VI]
“Wherein R1 and R2 are selected from H or OH with proviso that at least one of R1 and R2 is H”

According to sixth embodiment, present invention is to provides a process for the preparation of compound of Formula-VI,

[Formula-VI]
“Wherein R1 and R2 are selected from H or OH with proviso that at least one of R1 and R2 is H”
comprising reacting Tegoprazan of Formula-I,

[Formula-I]
with 3-hydroxybenzoic acid or 4-hydroxy benzoic acid in presence of solvent.
The solvent can be selected from the group consisting of alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, secondary-butyl alcohol or tert-butyl alcohol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; polar aprotic solvent such as dimethylsulfoxide, N,N-dimethylformamide or N-methylpyrrolidone; water; or mixture(s) thereof.
EXAMPLES:
The following examples are illustrative of some of the embodiments of the present invention described herein. These examples should not be considered to limit the spirit or scope of the invention in any way.
Example-01: Preparation of Tegoprazan Fendizoate of Formula-II
To a stirred solution of Tegoprazan (10.0 g) and dimethyl formamide (20 mL), Fendizoic acid (8.216 g) was added at 25°C to 35°C and stirred for 10 minutes at same temperature. The resulting mixture was heated at 60°C to 70°C to obtain a clear solution and maintained for 12 hours at the same temperature. The resulting solution was cooled slowly to 25°C to 35°C. The obtained solution is then added into purified water (100 mL) at same temperature and stirred for 1 hour. The solid precipitated was then filtered and washed with water (5 mL). Resulting solid was dried under vacuum at 50°C to 55 °C for 12 hours to obtained a title compound (18.0 gm) having purity of 99.8% by HPLC.

Example-02: Preparation of Tegoprazan Salicylate of Formula-IV
To a stirred solution of Tegoprazan (25 g) and methanol (125 mL), Salicylic acid (8.91 g) was added at 25°C to 35°C. Resulting reaction mixture was heated at 50°C to 55°C and stirred for 6 hours. Resulting mixture was then distilled to remove methanol completely to obtained a solid. n-Heptane (125 mL) was added to the resulting solid at 25°C to 35°C and stirred for 1.0 hour at same temperature. The resulting solid was filtered and washed with n-heptane (12.5 mL) to wet solid. Resulting wet solid was dried under vacuum at 50° to 55 °C for 12 hours to obtain a title compound (32.6 gm) having purity of 99.7% by HPLC.

The obtained amorphous form was stored at various conditions of relative humidity, and the XRPD was obtained up to 9 Months (Table 1):

Polymorph stability properties of Tegoprazan Salicylate amorphous (Example-02)
Temperature %Rh XRPD results- Initial XRPD results- after 3 months XRPD results- after 6 months XRPD results- after 9 months
25°C 60% Amorphous Amorphous Amorphous Amorphous
40°C 75% Amorphous Amorphous Amorphous Amorphous
Table-1
*HPLC result does not show any changes in comparison.

Example-03: Preparation of Tegoprazan Salicylate of Formula-IV
To a stirred mixture of 7-((S)-5,7-difluorochroman-4-yloxy)-N,N,2-trimethyl-3-tosyl-3H-benzo[d]imidazole-5-carboxamide (125.0 g) in acetonitrile (625 mL), aqueous sodium hydroxide [(46.2 g) NaOH in water (1250 mL)] was added at 50°C 60°C. After completion of reaction (monitored by HPLC), reaction mixture was extracted with methylene chloride (2 x 375 mL and 1 x 250 mL) and resulting organic layers were combined and washed with water (3 x 375 mL). The obtained organic layer was then distilled out under vacuum and methanol (500 mL) was added to distilled mass. Salicylic acid (22.55 g) was added to resulting solution at 25°C to 35°C. Resulting mixture was heated at 50°C to 55°C and stirred for 5 hours. The resulting mixture was then distilled till 1.0 volume solvent remains as such. Reaction mass is loaded to vacuum tray dryer and dried material under vacuum for 8.0 hours at 50°C to 60°C. n-Heptane (500 mL) was added to resulting solid and mixture was stirred for 1 hour at 20°C to 30°C. The resulting solid was filtered and washed with n-heptane (50 mL) to obtain wet solid. The resulting wet solid was dried under vacuum at 50°C to 60°C for 12 hours to obtain a title compound (90.0 g) having purity above 99.7% by HPLC.
Dated this 13th August 2024

Dr. Virendra Thakrar,
Sr. Vice- President R&D,
Ami Lifesciences Pvt. Ltd.

CLAIMS:I / We Claim:

1. A Tegoprazan Salicylate of Formula-IV,

[Formula-IV].

2. A stable amorphous Tegoprazan Salicylate of Formula-IV,

[Formula-IV],
when stored at 25°C and 60% relative humidity or
when stored at 40°C and 75% relative humidity does not convert to crystalline form.
3. The stable amorphous Tegoprazan Salicylate of Formula-IV according to claim 2, which does not convert to crystalline Tegoprazan Salicylate of Formula-IV for 9 months.
4. A process for the preparation of Tegoprazan Salicylate of Formula-IV,

[Formula-IV]

comprising reacting Tegoprazan of Formula-I,

[Formula-I]
with Salicylic acid of Formula-V,

[Formula-V]
to obtain a Tegoprazan Salicylate of Formula-IV.
5. The process as claimed in claim 04; wherein Tegoprazan of Formula-I is reacted with Salicylic acid of Formula-V in presence of solvent selected from the group consisting of alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, secondary-butyl alcohol or tert-butyl alcohol; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl isobutyl ketone; alkyl acetates such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate or isobutyl acetate; ethers such as diethyl ether, n-propyl ether, diisopropyl ether, methyl tertiary butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran or dimethoxyethane; nitriles such as acetonitrile, propionitrile, butyronitrile or isobutyronitrile; halogenated aliphatic hydrocarbons such as dichloromethane, dichloroethane, chloroform or carbon tetrachloride; aromatic hydrocarbons such as benzene, toluene or xylene; alkane such as n-hexane, n-heptane or cyclohexane or mixture(s) thereof.
6. The process as claimed in claim 04; wherein Tegoprazan of Formula-I is reacted with Salicylic acid of Formula-V in presence of solvent at temperature of 10°C to reflux temperature of solvent.
7. The process as claimed in claim 04; wherein Salicylic acid can be used in the range of 0.5 molar equivalent to 3.0 molar equivalent with respect to Tegoprazan of Formula-I.

Dated this 13th August 2024

Dr. Virendra Thakrar,
Sr. Vice- President R&D,
Ami Lifesciences Pvt. Ltd.