FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patent Rules, 2006
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. TITLE OF THE INVENTION: "PROCESS FOR THE PREPARATION OF
SUBSTITUTED AMINE HYDROCHLORIDE AND HYDRATES THEREOF - KEY RAW
MATERIAL FOR A LARGE NO OF PHARMACEUTICAL DRUGS".
2. APPLICANT
(a) NAME: ARCH PHARMALABS LIMITED
(b) NATIONALITY: INDIAN
(c) ADDRESS: "H" WING, 4™ FLOOR, TEX CENTRE, OFF SAKI
VIHAR ROAD, CHANDIVALI, ANDHERI (EAST), MUMBAI-400072, INDIA.
PREAMBLE TO THE DESCREPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

TITLE:
Process for the preparation of substituted amine hydrochloride and hydrates thereof - Key raw material for a large no of pharmaceutical drugs.
TECHNICAL FIELD OF THE INVENTION:
This invention relates to an efficient and economical process for the preparation of substituted amine hydro halides of formula I, particularly to N.N-dimethylamine hydrochloride of formula II and hydrates thereof; by reacting hydrochloric acid with respective substituted amine of formula III commonly in aqueous solution and subjecting it to instant evaporation & drying process to get the material with higher yield and high purity. This invention more particularly relates to a process of making anhydrous or hydrates of substituted amine hydro halides of formula I with special preference to N.N-dimethylamine hydrochloride of formula II by a novel technique of "instant evaporation & drying process" avoiding time consuming distillations followed by crystalisation, Alteration & drying used in conventional methods. The invention pertains to primary, secondary and tertiary amines used for the preparation of corresponding hydro halides. Substituted amine hydro halides are used as key intermediates for the preparation of a large no of APIs. Some examples are Ranitidine hydrochloride,Tramadol hydrochloride, amlodipine besylate and metformin hydrochloride. Disclosed herein is a process for the preparation of metformin hydrochloride wherein dimethylamine hydrochloride is used as an intermediate. Dimethylamine hydrochloride used as an intermediate for the preparation of APIs is prepared by a novel, efficient, economical and industrially viable process comprising instant evaporation & drying process.

Efficient thermal separation with minimum product decomposition and maximum product quality; these are results that we expect using the instant evaporation & drying process for drying. Performance of the said instant evaporation & drying process is far superior over conventional mode of distillation, crystallization & drying as known for the isolation of the compound of formula I particularly compound of formula II. A key to the superiority of this process under the invention includes short residence time of the feed and optimal efficiency in mass and heat transfer. The brief (seconds) exposure of feed which forces evaporation of the medium resulting in both energy and mass transfer through the droplet of the feed moving downward with strict control of residence time, droplet evaporation and flow characteristics. High quality components, state-of-the-art fittings and materials, and total quality control during all phases of design, fabrication and testing result in processing equipment offering the highest performance possible.

wherein Rl, R2 and R3 are independently alkyl group or hydrogen with atleast one alkyl group, X is halogen,
Formula I

wherein Rl and R2 are methyl groups and R3 is hydrogen
Formula II


whereinRl,R2and R3are injdependently alkyl group or hydrogen with atleast one alkyl group
Formula III BACKGROUND OF THE INVENTION:
Dimethylamine hydrochloride is a key raw material in the manufacture of the G-type nerve agent Tabun. It is also an important intermediate for the preparation of various drugs like Ranidine hydrochloride, Tramadol hydrochloride, Metformin hydrochloride and Amlodipine besylate.
The most important classical methods for the manufacture of alkyl amines is the reaction of alkyl Glides, such as methyl chloride, with ammonia. Alkyl amines such as Dimethylamine can be manufactured by a number of other methods including:
- catalytic amination of alcohols (methanol for dimethylamine); - catalytic alkylation of an aldehyde (formaldehyde) with ammonia or an amine.
These two methods give dimethylamine in a mixture with methylamine and trimethylamine thus require careful optimization of the process.
According to the currently practiced at industrial scale and state of the art disclosed in the prior art, dimethylamine hydrochloride is prepared by contacting of dimethyl amine gas with aqueous solution of hydrochloric acid (30- 34%) , continuous evaporation by age old method or distilling off water from the aqueous mass, tooling the concentrated reaction mass

to RT in the crystallizer to get crystalised mass, separation of solid mass by centrifuge and drying the wet cake in the FBD or in the vacuum dryer. The major drawback of this multi-operational conventional method is the removal of water by distillation technique which is a very lengthy operation.
Dimethylamine hydrochloride obtained according to the process disclosed in the prior art and currently being practiced in the industry is of low purity having dull color and the process is uneconomical as it comprises the long time period for the evaporation or distillation of water from the reaction mass thereby contributing towards higher overheads that includes energy consumption, manpower, Lower yield, less purity, dull color of the product etc..In case of vacuum drying corrosion of the vacuum dryer as it comprises hydrochloride.
Journal of Organic Chemistry; vol. 70; No. 5; (2005); p. 1897 - 1900 discloses the preparation of N.N-dimethylamine hydrochloride by debenzylation on N,N-dimethyl benzyl amine using, hydrogen, palladium on activated charcoal in methanol followed by its conversion into hydrochloride by passing dry hydrogen chloride and cooling the mass to crystallize the product. Drawback associated with this method is the use of costly metals like palladium, platinum used for catalytic debenzylation.
US5026838, Inorganic Chemistry; vol. 5; (1966); p. 457 - 461, Inorganic Chemistry; vol. 20; (1981); p. 1859 - 1866 discloses dimethylamine hydrochloride obtained as a by-product for which dimethylamine is used as an acid scavenger for outgoing hydrogen chloride gas. However there is no mention of drying or purity of the dimethylamine hydrochloride obtained in the process. Dimethylamine hydrochloride obtained as a byproduct remains contaminated with the actual product of the reaction,

therefore, unsuitable for use as a raw material or intermediate for the preparation of pharmaceutical drugs.
The important operational step for the preparation of dry dimethylamine hydrochloride or hydrates thereof is to dry the aqueous mass obtained after contacting dimethyl amine with aq. HC1 and the processes being practiced currently and disclosed in the prior art comprising distillation, oven heating, vacuum drying are inefficient, uneconomical and the product obtained according to processes disclosed therein in the prior art is of dull colour and low purity. In view of above there is a dire need to develop a process to prepare white and substantially pure dry dimethylamine hydrochloride which overcomes the shortcomings of the processes disclosed in the prior art and currently being practiced in the industry.
Disclosed herein in the present invention is a novel process of drying of N.N-dimethylamine hydrochloride comprising instant evaporation & drying process selected from spray drying; drum drying, agitated thin film dryer and the like preferably spray drying.
OBJECT OF THE INVENTION:
First aspect of the invention is to provide an efficient and novel technique for the drying of substituted amine hydro halides of formula I and hydrates thereof.
Second aspect of the invention is to provide an efficient and novel technique for the drying of N.N-dimethylamine hydrochloride formula II and hydrates thereof.
Third aspect of the invention is to provide an efficient process for the preparation of substituted amine hydro halides of formula I and hydrates

thereof comprising contacting anhydrous substituted amine and aqueous hydrohalic acid and to dry resulting reaction mass by instant evaporation & drying process.
Fourth aspect of the invention is to provide an efficient process for the preparation of substituted amine hydro halides of formula I and hydrates thereof comprising contacting aqueous substituted amine and aqueous hydrohalic acid and to dry resulting reaction mass by instant evaporation & drying process.
Fifth aspect of the invention is to provide an efficient process for the preparation of substituted amine hydro halides of formula I and hydrates thereof comprising contacting aqueous substituted amine and gaseous hydrohalic acid and to dry resulting reaction mass by instant evaporation & drying process.
Sixth aspect of the invention is to provide an efficient process for the preparation of N.N-dimethylamine hydrochloride of formula II and hydrates thereof comprising contacting anhydrous N.N-dimethylamine and aqueous hydrochloric acid and to dry resulting reaction mass by instant evaporation & drying process.
Seventh aspect of the invention is to provide an efficient process for the preparation of N.N-dimethylamine hydrochloride of formula II and hydrates thereof comprising contacting aqueous N.N-dimethylamine and aqueous hydrochloric acid and to dry resulting reaction mass by instant evaporation & drying process.
Eighth aspect of the invention is to provide an efficient process for the preparation of N.N-dimethylamine hydrochloride of formula II and hydrates thereof comprising contacting aqueous N.N-dimethylamine and

gaseous hydrochloric acid and to dry resulting reaction mass by instant evaporation & drying process.
Ninth aspect of the invention is to provide an efficient process for the drying of aqueous mass of substituted amine hydrochloride particularly N.N-dimethylamine hydrochloride obtained after contacting respective amines and hydrohalic acid avoiding distillation like techniques.
Tenth aspect of the invention is to provide an efficient process for the preparation of substituted amine hydro halides of formula I and hydrates thereof with high yield and high purity.
Eleventh aspect of the invention is to provide an ideal process wherein the end-product must comply with precise quality standards regarding particle size distribution, residual moisture content, bulk density, morphology, color like parameters.
Twelfth aspect of the invention is to provide the process for the preparation of APIs comprising the use of substituted amine hydro halides or hydrates thereof preferably N.N-dimethylamine hydrochloride made by novel technique for its drying.
Thirteenth aspect of the invention is to provide the process for the preparation of metformin hydrochloride comprising the use of N.N-dimethylamirie hydrochloride made by novel technique for its drying.
SUMMARY OF THE INVENTION:
Disclosed herein is a process for the preparation of substituted amine hydro halides of the formula I and hydrates thereof, particularly N.N-dimethylamine hydrochloride of formula II and hydrates thereof comprising contacting anhydrous or aqueous dimethylamine and

aqueous or dry hydrochloric acid and the resulting aqueous reaction mass is then subjected to instant evaporation & drying process. The present invention also relates to a process for the preparation of APIs preferably metformin hydrochloride comprising the use of N.N-dimethylamine hydrochloride of formula II and hydrates thereof dried by the technique under the present invention.
DETAILED DESCREPTION OF THE INVENTION:
Contacting hereinabove and hereinbelow means reacting, mixing, condensing, stirring, heating or combination thereof and the like.
Inventors of the present invention have prepared dimethylamine hydrochloride of formula-II according to the classical method reported therein in the prior art comprising drying the reaction mass containing the said desired material by the classical prior art techniques such as distillation of the water from the reaction mass, vacuum drying, oven drying and found that it yielded only 65% having off white colour with less productivity, more energy consumption, more man power. Therefore, it was thought worthwhile to develop an efficient mode of drying for the said compound that gives the substantially pure white coloured material in higher yield and the process requires less energy, and manpower and the like.
Inventors of the present invention have disclosed herein a novel method of instant evaporation & drying of reaction mass obtained by contacting substituted aliphatic amine with optionally aq. Hydrogen halide comprising spray drying skipping an operational step of centrifuging to obtain substantially pure white coloured dry hydrogen halide and hydrates thereof in about 92-95% yield. The novel process of spray drying of reaction mass comprising substituted aliphatic amines and

hydrates thereof is economical, ecofriendly as it requires less power/energy and manpower resources.
Table-I given hereinbelow in a vivid manner demonstrates the advantages of the novel process of instant evaporation & drying preferably spray drying of dimethylamine hydrochloride compared to classical methods reported therein in the prior art and currently being practiced in the industry for the preparation of dimethylamine hydrochloride.
The process- of instant evaporation & drying preferably spray drying disclosed herein for the preparation of substituted aliphatic amine hydrogen halides and hydrates thereof is an ideal process wherein the end-product complies with precise quality standards in respect of colour, particle size distribution, residual moisture content, bulk density, morphology and the like. Interest in pharmaceutical spray drying is driven by a number of advantages over conventional multiple-step drying processes and competing particle size reduction technologies.
The two main spray techniques are spray drying & spray congealing. The action in spray drying is primarily that of evaporation, whereas in spray congealing it is that of a phase change from a liquid to a solid. The two processes are similar, except for energy flow. In the case of spray drying, energy is applied to the droplet, forcing evaporation of the medium resulting in both energy and mass transfer through the droplet. In spray congealing, energy only is removed from the droplet, forcing the melt to solidify.
Spray dryers units operate generally with nitrogen or air as the drying gas and are fit to handle both aqueous and organic feeds (solutions, emulsions and pumpable suspensions and the like).

There are three fundamental steps (figure 1) involved in spray drying.
1) Atomization of a liquid feed into fine droplets.
2) Mixing of these spray droplets with a heated gas stream, allowing the liquid to evaporate and leave dried solids.
3) Dried powder is separated from the gas stream and collected.
Spray drying comprises the atomization of a liquid feedstock into a spray of droplets and contacting the droplets with hot air in a drying chamber.
Following figure 1 represents all the important stages of spray drying:

Figure - 1 Main process stages involved in spray drying process
Evaporation of moisture from the droplets and formation of dry particles proceed under controlled temperature and airflow conditions (Figure- 2). Powder is discharged continuously from the drying chamber. Operating conditions and dryer design are selected according to the drying characteristics of the product and powder specification.


Figure- 2 Formation of product in spray drying
In a general embodiment of the present invention disclosed herein is a process for the preparation of substituted amine hydro halides of the formula I and hydrates thereof comprising contacting the compound of formula III with hydrohalic acid resulting into a reaction mass which is then subjected to spray drying to obtain a substantially pure substituted amine hydro halides of formula I and hydrates thereof which can be used as an intermediate for the preparation of APIs.
Schematic presentations of the present invention is depicted as given below:




Temperature for the said reaction may be any as long as it does not inhibit the reaction or which either does not impart the impurity formation or that forms the impurity that is manageable to be removed.
The stoichiometric ratio of the reactants viz. compounds of formulae III, and hydrohalic acid may be any as long as it does not inhibit the reaction or does not impart the impurity formation that is not manageable.
Referring to a preferred aspect of the invention, disclosed herein is a process for the preparation of N.N-dimethylamine hydrochloride of formula II and hydrates thereof comprising contacting of aqueous hydrochloric acid with anhydrous dimethyl amine at a suitable temperature resulting in a reaction mass which is then subjected to spray drying resulting into substantially pure N.N-dimethylamine hydrochloride of formula II or its hydrate thereof. The said N.N-dimethylamine hydrochloride is used for the preparation of APIs.
Schematic presentations for the said invention' are depicted as given below:


Referring to another preferred aspect of the invention, disclosed herein is a process for the preparation of N.N-dimethylamine hydrochloride of formula II and hydrates thereof comprising contacting of aqueous hydrochloric acid with aqueous dimethyl amine at a suitable temperature resulting in a reaction mass which is then subjected to spray drying resulting into substantially pure N.N-dimethylamine hydrochloride of formula II or its hydrate thereof. The said N.N-dimethylamine hydrochloride is used for the preparation of APIs.

Referring to one more preferred aspect of the invention, disclosed herein is a process for the preparation of N.N-dimethylamine hydrochloride of formula II and hydrates thereof comprising contacting of aqueous hydrochloric acid with dry dimethyl amine at a suitable temperature resulting in a reaction mass which is then subjected to spray drying resulting into substantially pure N.N-dimethylamine hydrochloride of formula II or its hydrate thereof. The said N.N-dimethylamine hydrochloride is used for the preparation of APIs.


In another preferred embodiment of the invention disclosed herein is a process for the preparation of metformin hydrochloride of formula V comprising contacting of N.N-dimethylamine hydrochloride of formula II dried by the novel technique disclosed herein under the present invention with dicyanodiamide of formula IV in a standard method reported in the prior art US2011/0021634

To summarize the present invention, it comprises the following steps:
1. The reaction mass obtained by contacting aqueous hydrochloric acid with anhydrous dimethylamine gas is feeded to the spray dryer drying chamber through high speed atomizer.
2. The reaction mass obtained by contacting aqueous hydrochloric acid with aqueous dimethylamine gas is feeded to the spray dryer drying chamber through high speed atomizer.
3. The reaction mass obtained by contacting dry hydrochloric acid with aqueous dimethylamine gas is feeded to the spray dryer drying chamber through high speed atomizer.

4. With the help of atomizer, feed will be converted into fine droplets & it will get instantantly dried by coming in contact with hot air.
5. Dried product will be carried forward along with hot air to the cyclone chamber.

6. Finally, dried product will collected from the bottom of cyclone under controlled atmosphere.
7. Hot air outlet from cyclone chamber will be finally passing through the scrubber before discharge to atmosphere.
The term "the reaction mass" stated hereinabove and hereinbelow relates to the mass obtained after contacting optionally aqueous hydrohalic acid and optionally aqueous substituted amine gas and could be in the form of solution, suspension or emulsion.
The term "hydrate" stated hereinabove and hereinbelow means permissible acceptance of water molecules resulting into water of crystallization.
The term "substituted amine: used hereinabove and hereinbelow means amine could be primary, secondary, tertiary amine and also could be quartanary ammonium salts.
It will be apparent to those skilled in the art that the various modifications and variations can be made in the present invention and specific examples provided herein without departing from the spirit or scope of the invention. Thus, it is intended that the present invention covers the modifications and variations of this invention that come within the scope of any claims and their equivalents.

The following examples are for illustrative purposes only and are not intended, or should they be interpreted to limit the scope of the invention.
Example 1: 57 Kg of anhydrous DMA gas was purged in 147 Kg of aqueous HC1 keeping the temperature in the range of 30 to 50°C giving 200 kg of reaction mass, which was then subjected to instant evaporation & drying by using spray dryer.
Conditions of spray drying:
Inlet air temperature- 120 to 300°C
Outlet air temperature 90 to 180°C.
Product output - 94 kg (Yield 92%)
Analytical results of the output product:
Appearance: White crystalline powder
pH- 5.2 (1 gm dissolved in 10 ml of water)
Assay: 99 % non aqueous titration
Moisture content: 0.17 % (karlfisher)
Example 2: 285 Kg of anhydrous DMA gas was purged in 730 Kg of aqueous HC1 keeping temperature in the range of 30 to 50°C giving 1000 kg of reaction mass, this 1000 Kg of reaction mass was subjected to instant evaporation & drying by using spray dryer.
Conditions of spray drying:

Inlet air temperature of 120 to 300°C Outlet air temperature 90 to 180°C
Product output - 482 kg (95%)
Analytical results of the output product:
Appearance: White crystalline powder
pH- 5.1 ( 1 gm dissolved in 10 ml of water)
Assay: 99 % non aqueous titration
Moisture content: 0.19% (karlfisher)
Example 3: 570 Kg of anhydrous DMA gas was purged in 1466 Kg of aqueous HC1 keeping in the range of 30 to 50°C giving 2000 kg of reaction mass, this 2000 Kg of reaction mass was subjected to instant evaporation & drying by using spray dryer.
Conditions of spray drying -
Inlet air temperature 120 to 300°C
Outlet air temperature 90 to 180°C
Product output - 985 kg.
Analytical results of the output product:
Appearance: White crystalline powder
pH- 5.2 ( 1 gm dissolved in 10 ml of water)

Assay: 99 % non aqueous titration Moisture content: 18% (Monohydrate)
Example 4 : 112.5 grams of aqueous dimethylamine was purged with dry 36.5 g of dry hydrogen chloride keeping the temperature in the range of 30 to 50°C giving 158 gram of aqueous reaction mass which was then subjected to spray drying.
Conditions of spray drying:
Inlet air temperature 120 to 300°C
Outlet air temperature 90 to 180oC
Product output - 75grams. (92%)
Analytical results of the output product:
Appearance: White crystalline powder
pH- 5.1 ( 1 gm dissolved in 10 ml of water)
Assay: 99 % non aqueous titration
Moisture content: 0.19% (karlfisher)
Example 5 : 112.5 grams of aqueous dimethylamine was contacted with 114 grams of 32% aqueous hydrochloric acid keeping the temperature below 50°C giving 228 gram of aqueous reaction mass which was then subjected to spray drying.
Conditions of spray drying:

Inlet air temperature 120 to 300°C
Outlet air temperature 90 to 180°C
Product output - 70 grams. (86%)
Analytical results of the output product:
Appearance: White crystalline powder
pH- 5.1 ( 1 gm dissolved in 10 ml of water)
Assay: 99 % non aqueous titration
Moisture content: 0.19% (karlfisher)
Example 4: Preparation of Metformin Hydrochloride:
Xylene (400 mL) and dicyanodiamide (100 g) were taken in a round-bottom flask. The reaction mixture was heated at 80° C. Dimethylamine hydrochloride (117 g) obtained from any of the example above was added portion-wise within 2 hours. The reaction mass was stirred for 3 hours. The reaction mixture was further heated to 100° to 105°C followed by heating to 140° C. The reaction mass was stirred for 4 hours and cooled to 95° C. The reaction mass was treated with water (200 mL) and layers were separated. The organic layer was again extracted with water (50 mL). The combined aqueous layer was treated with charcoal (3 g) and stirred for 20 minutes. The reaction mass was filtered through a hyflowbed and washed with water (50 mL). The filtrate was taken in a round-bottom flask at 50° C. and N 2 gas was purged for 30 minutes. The filtrate was distilled to remove water completely under vacuum at 65°C. The residue thus obtained was treated with methanol (110 mL) at 40°C to 45°C and cooled to 20°C to 25°C. The product was filtered and washed with chilled methanol (50 mL). The wet-cake thus obtained was

treated with water at 50°C along with N 2 gas contacting for 30 minutes, The solution was distilled to remove water completely under vacuum at 65 °C The residue thus obtained was treated with methanol (80 mL) at 40°C to 45°C to prepare the slurry. The slurry was pulverized under high-speed grinder for wet grinding for 25 minutes. The reaction mass was filtered and dried. The wet-cake was washed with chilled methanol (30 mL). The product was dried at 65°C to 70°C to obtain 160 g metformin hydrochloride.

Comparison Table: Table-I

Sr.No Parameter Prior art
manufacturing
method Present
Invent'on Savings / Advantages
1. Productivity: 156.25 Kg /Hour 568.2 Kg/ Hour 3.6 times more productivity.
2. Manpower 29 Nos / day 10 Nos /day Aprox 65% saving.
3. Energy consumption 68.62 kw/hour 54.61 Kw/hour Rs. 27946 / day
4. Fuel Rs 5.76 for1 Kg DMA Rs 3.92 for 1 Rs 25092/day
consumption HC1 production Kg DMA HCl production
5. Quality White to off white White powder Since material is
powder,
KF- around 0.5% KF-<0.1% hygroscopic, so its KF <0.1% is major
advantage.
6. Environmental • Chances of spillage • No chance
impact during pumping operations at several stages.
• Distillation results
in localized heating
of product, due to
constant heating /
vaporization..
• Due to constant
heating /
continuous
evaporation of
reaction mass,
atmosphere is
adversely affected
by this continuous
vapourisation. of spillage as directly material is
pumped only at the
time of feeding-• Required small Place.
• No such effect to atmosphere
6. Safety Manual handling operations Fully automated system in close loop. . More safe.

WE CLAIM:
1. A process for the preparation of substituted amine hydrohalides of the formula I and hydrates thereof

wherein Rl, R2 and R3 are independently alkyl group or hydrogen with atleast one alkyl group, X is halogen,
Formula I
comprising:
a) contacting optionally aqueous hydrohalic acid H-X wherein X is a
halogen selected from CI, Br or I with optionally aqueous substituted
amine of formula III

wherein Rl. R2 and R3 are independently alkyi group or hydrogen with atlieast one alkyl group
Formula III
b) subjecting reaction mass obtained from the step a to instant
evaporation & drying and collecting the dry product.
2. Reaction mass as stated in claim is a solution, suspension or emulsion and the like.

3. Substituted amine as stated in claim lis selected from the group of primary, secondary, tertiary amine and also could be quartanary ammonium salts.
4. A process for the preparation of N,N-dimethyIamine hydrochloride of formula II
wherein Rl and R2 are methyl groups and R3 is hydrogen
Formula II
comprising:
a) contacting optionally aqueous dimethylamine with optionally aqueous
hydrochloric acid
b) subjecting reaction mass obtained from the step a to instant
evaporation & drying and collecting the N,N-dimethylamine
hydrochloride and hydrates thereof.
5) Reaction mass as stated in claim 4 is solution, suspension or emulsion and the like.
6) A process for the preparation of active pharmaceutical ingredient (API) comprising using substituted amine hydrohalide made by the process as claimed in claim 1.
7) A process for the preparation of active pharmaceutical ingredient (API) comprising the use of N,N-dimethylamine hydrochloride and hydrates thereof made by the process as claimed in claim 4.

8) Active pharmaceutical ingredient (API) as claimed in claim 7 is
selected from the group comprising of Ranidine hydrochloride,
Tramadol hydrochloride, Metformin hydrochloride and Amlodipine
besylate especially Metformin hydrochloride.
9) A process for the preparation of metformin hydrochloride of formula
V comprising contacting dicyandimide of formula IV

Metformin Hydrochloride
with N,N-dirnethylamine hydrochloride of formula II prepared by the process as claimed in claims 1 and 4.
10) A process for the preparation of metformin hydrochloride of formula V comprising


a) contacting optionally aqueous dimethyl amine with optionally
aqueous hydrochloric acid
c) contacting dicyandimide of formula IV
b) subjecting reaction mass obtained from the step a instant evaporation
& drying and collecting the N,N-dimethylamine hydrochloride of
formula II and hydrates thereof.


with N,N-dimethylamine hydrochloride of formula II prepared by the process as claimed in claims 1 and 4.
11) The instant evaporation & drying as claimed in claims 1,4, 10 is spray drying.