FORM 2
THE PATENT ACT 1970 (39 of 1970)
SL
The Patents Rules, 2003 COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
"AN IMPROVED PROCESS FOR SYNTHESIS OF METFORMIN HYDROCHLORIDE"
2. APPLICANT (S)
(a) NAME: Wanbury Ltd.
(b) NATIONALITY: An Indian Company incorporated under the Indian Companies ACT 1956.
(c) ADDRESS:
Wanbury Ltd. , BSEL Tech park, B-wing, 10th floor, sec -30A, opp.
Vashi Railway station, Vashi, Navi- Mumbai-400703, India.
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

AN IMPROVED PROCESS FOR SYNTHESIS OF METFORMIN
. HYDROCHLORIDE
TECHNICAL FIELD:
The present invention relates to an improved, cost effective, solvent free green process for synthesis of highly pure Metformin hydrochloride substantially free from Melamine, Dimethylamine, (4,6-diamino-1,3,5-triazin-2-yl)guanidine and Cyanoguanidine.
BACKGROUND OF THE INVENTION:
Metformin is a typical biguanide, chemically known as (N, N- dimethyl imidocarbonimidic diamide). Metformin is an oral antihyperglycemic drug used in the management of non-insulin-dependent diabetes mellitus (NIDDM). It is typically used as pharmaceutically acceptable salt preferably Hydrochloride salt. Metformin Hydrochloride is currently marketed as GLUCOPHAGE® tablets by Bristol-Myers Squibb Co. Each GLUCOPHAGE® tablet contains 500, 850 or 1000 mg of Metformin Hydrochloride. There is no fixed dosage regimen.for the management of hyperglycemia in diabetes mellitus with GLUCOPHAGE®. Dosage of GLUCOPHAGE® is individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended dose of 2550 mg per day.
Metformin hydrochloride is a white to off white crystalline compound with bitter taste having molecular

formula C4H11N5 HC1 with molecular wt of 65.63. Metformin hydrochloride is freely soluble in water and practically insoluble in acetone, ether and chloroform. Its structure was generally represented in a wrong tautomeric form for several years, but that was corrected in 2005 and is represented by formula I as given below.
Metformin hydrochloride is used for Type II diabetes, every diabetic patient taking approximately 1000 mg of Metformin every day of the year.
If only two thirds of the global diabetic population (.285 million) consumes the medicine and Metformin was the drug of choice, then about 69,000 metric tons per year (about 152 million pounds per year) of Metformin hydrochloride (Active Pharmaceutical Ingredient) would be needed. This is a significantly large quantity of a specialty chemical that has a disease curing value. At this volume, it should be produced by a commercially efficient process.
U.S. Patent No. 3,174,901 discloses composition
containing dimethyl biguanide used in the form of
hydrochloride salt wherein it is used for treating
diabetes by oral administration.
Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide hydrochloride) of formula lis a member of the biguanide class of oral antihyperglycemic which improves

glucose tolerance in patients with type II diabetes, lowering both basal and postprandial plasma glucose.
Metformin is absorbed incompletely and predominantly from the small intestine, with fecal recovery being about 30% of an oral dose. Oral absorption of metformin occurs within 6 hours, with an expected bioavailability of 50 to 60%. The drug is stable, does not bind to plasma proteins and is excreted unchanged in the urine. The difference between absorbed and available drug may reflect minor presynaptic clearance of the drug or binding to the intestinal wall. Concomitant food intake may slightly impair metformin absorption. The plasma concentrations are up to 2 jjg/ml 1 to 2 hours after an oral dose of 500 to 1000 mg.
Metformin hydrochloride of formula I is commercially manufactured by condensation of dimethyl amine of formula II in the form of hydrochloride and dicyandiamide, also called as cyanoguanidine of formula III as shown below in scheme-1.
During this condensation, number of impurities are formed which are present in Metformin hydrochloride along with starting materials. Major impurities so far detected in

commercial Metformin hydrochloride are dimethyl amine of formula II, Cyanoguanidine of formula III, 1,3,5-triazine-2,4,6-triamine or melamine of formula IV, (4,6-diamino-1,3,5-triazin-2-yl)guanidine of formula V, N,N-dimethyl-1,3,5-triazine-2,4,6-triamine or N,N-dimethyl melamine of formula VI and 1-methyl biguanide of formula VII. The chemical structures of impurities and epimeric impurities are as showon below in Table-1.
Table-1:

Name
Dimethyl amine
Cyanoguanidine
1,3,5-triazine-triamine or Mel 2,4,6-.amine
(4,6-diamino-l, triazin-2-yl)gu 3,5-lanidine
N,N-dimethyl-l, triazine-2,4,6-N,N-dimethyl me 3,5-
triamine or diamine
1-methyl biguanide
All the impurities listed above, are potentially hazardous to human health. Literature references related to toxicological studies of first four important

impur ties are as follows
Dimethyl amine Hydrochloride of formula II: Dimethyl amine is the immediate precursor of dimethylnitrosamine, a known potent carcinogen in a wide variety of animal species [Food and Chemical Toxicology 36, 3, 923-927, (1998)] Olfactory sensory cells are highly sensitive to the toxic effects of dimethyl amine {Buckley et al. Toxicol. Sci. 5, 341-352 (1985)}.
Cyanoguanidine of formula III:
The body weight gains are significantly lowered due to intake of Cyanoguanidine [K. Yasuhara et al. Food and Chemical Toxicology 35, 475-480(1997)]. The substance may decomposes on heating or reaction with acid to produce toxic gases including ammonia and hydrogen cyanide.
Melamine of formula IV:
Repeated dose toxicity studies of melamine shows that melamine produces urinary bladder stones (urolithiasis), hyperplastic epithelial changes in the urinary bladder and calcerous deposits in the proximal kidney tubules. Long term effects noted are inflammation and occurrence of transitional cell papillomas and carcinomas of the urinary bladder. {MelnickR. L. etal. Toxicol. Appl. Pharmacol. 72, 292-303 (1985)}.
(4,6-diamino-l,3,5-triazin-2-yl)guanidine of formula V: The substance may decomposes on heating or reaction with acid to produce toxic gases including ammonia and

hydrogen cyanide {Research & Reviews: Journal of Pharmaceutics & Nonaotechnology, Vol. 2 (Jul-Sept 2014)}.
Limits of those impurities in Pharmacopoeia or as per ICH guidelines are very stringent, 0.02% (200 ppm) for Cyanoguanidine of formula III, 180 ppm for dimethylamine of formula II and 0.0011% as limit of detection for Melamine of formula IV, 0.05% for (4, 6-diamino-l,3,5-triazin-2-yl) guanidine of formula V, whereas the limit of 0.05% (500 ppm) for any single individual and 0.3% (3000 ppm) for total impurities.
It means a person consuming 1000 mg tablet of Metformin a day, possibly consumes -110 mgs of impurities listed above, which are potentially hazardous to human health.
The first synthesis of metformin was reported in 1922 by Werner and Bell from Trinity college of Dublin, Ireland and then Jean Sterne discovered it as an antidiabetic agent in Paris.
Germany Patent Application No. 1023757 discloses preparation of Metformin hydrochloride by reacting dicyanodiamide with dimethyl amine hydrochloride in xylene at reflux temperature followed by decantation of xylene and crystallization from water to obtain Metformin hydrochloride with a very low yield of only 47%.
Indian Patent No, 189077 discloses preparation of Metformin hydrochloride by reacting dicyanodiamide with

dimethyl amine hydrochloride in presence of wet Metformin hydrochloride at a temperature not exceeding 150°C followed by addition of water, evaporation and crystallization of the solution to obtain Metformin hydrochloride.
U.S Patent Publication No. 2011/021634 discloses preparation of Metformin hydrochloride substantially free from dimethyl amine wherein an aqueous solution of Metformin hydrochloride is concentrated to remove water completely under vacuum at 65°C and further involves pulverization technique.
Indian Patent Application No. 1350/MUM/2007 publication discloses preparation of highly pure Metformin hydrochloride substantially free from melamine and cyanoguanidine impurities by condensation of dimethylamine hydrochloride with dicyandiamide in xylene; extracting followed by distilling the product under vacuum at 65-72°C and crystallizing Metformin hydrochloride from methanol or a mixture of water and methanol.
PCT Publication No. 2014/041566 discloses the process wherein Metformin hydrochloride obtained guanidine impurity less than 0.05% by extracting Metformin hydrochloride in water followed by subjecting it to expensive techniques such as agitated thin film dryer (ATFD) for water removal.

The methods known in the art for the preparation of Metformin hydrochloride involve removal of water by either distillation under vacuum or by expensive equipments like agitated thin film dryer (ATFD) prior to isolation of the product. This is one of the enormous disadvantage with the known processes involve prolonged period of water distillation and use of huge amount of organic (hydrocarbon) solvents rendering the process expensive and most cumbersome on commercial scale.
To overcome these difficulties associated with the vacuum distillation or use of ATFD techniques to isolate Metformin hydrochloride from water medium, use of vacuum at lower temperatures or ATFD dryer use is preferred, but this again takes longer period of time and huge capital investments and maintenance. Others methods commercially available requires huge energy costs, apart from these disadvantages; these methods are not environment friendly and it may further exert to contribution of impurity profile.
Accordingly, there remains a need in the art for the preparation of highly pure Metformin hydrochloride which will contain impurity level well below regulatory permissible limits and circumvents the aforementioned difficulties in cost effective and commercially viable methods, which is invented in present invention.
The current manufacturing of Metformin hydrochloride involves a well-known and proven process. The process

includes the dissolution and reaction, followed by the precipitation of Metformin Hydrochloride. Although reliable and effective, the current process relies on the use of a solvent; which later needs to be eliminated from the precipitates.
The present invention is an alternative reaction pathway which avoids the use of solvent (s) and simplifies and makes the process green. The key benefits include reduced costs, time and energy saving for the processing and a final product which meets all the Pharmacopeia quality standards.
Green Chemistry, the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances is an overarching approach that is applicable to all aspects of chemistry. All synthetic processes involve the use of different solvents. Unfortunately many of the solvents are used in industry and retail are volatile organic compounds (VOCs) which lead to environmental damage, through pollution, risks to human health and to resource depletion, we need to develop and apply more environmentally friendly approaches. So, all traditional and old synthetic routes obviously give adverse effects to the mankind and all living beings. Green chemistry provides "Green" paths for different synthetic routes using non-hazardous solvents and environmental-friendly chemicals. Solvent free synthesis has several advantages over the classical method of synthesis. Due to enormous advantages of

solvent free reactions, new solvent-free approaches are being discovered for eco-friendly synthesis of many compounds.
OBJECTS OF THE INVENTION:
The main object of the invention . is to provide an
improved process for synthesis of highly pure Metformin
hydrochloride which is cost effective and commercially
viable with high throughput with substantially free from
cyanoguanidine of formula (HI), dimethylamine
hydrochloride of formula (II), melamine of formula (IV) and (4,6-diamino-l,3,5™triazin-2-yl)guanidine of formula (V) impurities by employing greenf solvent free process.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide an improved, cost effective, solvent free green process for synthesis of highly pure Metformin hydrochloride of formula I.
Another aspect of the present invention is to provide an improved process for synthesis of highly pure Metformin hydrochloride comprises; reacting dimethyl amine hydrochloride with cyanoguanidine in solvent free conditions to obtain Metformin hydrochloride substantially free from the impurities cyanoguanidine of formula III, dimethylamine hydrochloride of formula II,

melamine of formula IV and (4,6-diamino-l,3,5-triazin-2-yl)guanidine of formula V.
Another aspect of the present invention is to provide an improved process for synthesis of highly pure Metformin hydrochloride comprising the steps of:
a) reacting dimethyl amine hydrochloride with cyanoguanidine in solvent free condition, and
b) isolating highly pure metformin hydrochloride.
Another aspect of the present invention is to provide an improved process for' synthesis of highly pure Metformin hydrochloride, wherein highly pure Metformin hydrochloride exhibit anticacking property with particle size (D90) less than 200 \im.
DETAILED DESCRIPTION OF THE INVENTION:
The present invention encompasses an improved, green process for synthesis of highly pure Metformin hydrochloride under solvent free condition, which avoids the use of large amount of solvent for the reaction of cyanoguanidine with dimethyl amine hydrochloride and without using conventional distillation techniques as well as modern techniques such as ATFD there by process exert more convenient, cost effective and economical, particularly on commercial scale. The term highly "pure Metformin hydrochloride" refers Metformin hydrochloride having purity more than 99.9% and the term "high yield of metformin hydrochloride" refers to more than 94% yield.

The term "anticacking" means preventing formation of lumps or sticky mass or solid blocks.
In another embodiment, the present invention provide an improved process for- synthesis of highly pure Metformin hydrochloride, wherein the reaction of dimethyl amine hydrochloride with cyanoguanidine may be carried out at a temperature in the range of 70°C to 160°C for a period of 2 hours to 12 hours in solvent free condition.
After completion of the reaction, the resulting Metformin hydrochloride may be further purified through solvent slurry.
The suitable solvent used herein for solvent slurry may be selected from but not limited to methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol and the like or mixture(s) thereof.
The highly pure Metformin hydrochloride may be isolated by conventional techniques such as filtration. The product may optionally be further dried in any conventional drier process.
The isolated highly pure Metformin hydrochloride may be further dried at a temperature in the range of 80-85°C for a period of 8-12 hours.

In another embodiment, the present invention provides an improved process for synthesis of highly pure Metformin hydrochloride comprising the steps of:
a) charging dimethylamine hydrochloride and cyanoguanidine as solid in to the reactor;
b) heating mixture of dimethylamine hydrochloride and dicyanodiamide at 70-140°C without any solvent;
c) maintaining the molten mass of dimethylamine hydrochloride and cyanoguanidine at 110-120 °C;
d) filtering molten reaction mass through Pharma filter aid;
e) heating the filtered molten reaction mass at 130-150°C by maintaining temperature for 3-5 hrs without vacuum or optionally with vacuum;
f) cooling the reaction mass at temperature 55-60°C;
g) charging 1-2 volumes of methanol and maintaining reaction mass at 55-60°C;
h) cooling the reaction mass to 25-30°C and filtered or
optionally repeat the steps g and h ;and i) dry the obtained solid in step h at temperature 8 0-85
°C for 8-12 hrs,
The molar ratio of cyanoguanidine and dimethyl amine hydrochloride is 1.0:1.13-1.19 respectively, more preferably 1.0: 1.18. The cyanoguanidine is added in dimethyl amine hydrochloride either in one lot or optionally more than one lot.

The obtained highly pure Metformin hydrochloride exhibit anticacking property with particle size (D90) less than 200 ]om.
The present invention provides process for synthesis of Metformin hydrochloride substantially free from all the impurities i.e. cyanoguanidine .of formula III, dimethylamine hydrochloride of formula II, me1amine of formula IV and (4,6-diamino-l,3,5-triazin-2-yl)guanidine of formula V, so far present in commercial Metformin hydrochloride processes available in prior arts. Present invention, provides highly pure Metformin hydrochloride with high yields.
All impuritie (s) specified above are well below the limits specified by pharmacopeia or regulatory bodies. For instance, Cyanoguanidine (Formula III) content obtained by the present invention is 0.002% against pharmacopeia limit of 0.02%, and Melamine (formula IV) content obtained by the present invention is 0.0001% against pharmacopeia limit of 0.0011% limit of detection.
Dimethylamine (formula II) content obtained by the present invention is less than 30 ppm (parts per million) against pharmacopeial limit of 180 ppm and (4,6-diamino-1,3,5-triazin-2-yl)guanidine(formula V) content obtained by the present invention is 0.0002% against pharmacopeia limit of 0.05%. Single unidentified impurity, obtained by the present invention is 0.01% against pharmacopeia limit

of 0.05% and total impurities obtained by the present invention is 0.04% against pharmacopeia limit of 0.3%.
The major advantage of present invention is to provide process for preparation of metformin hydrochloride which is eco-friendly, solvent free process over the conventional and prior arts process. The present invention process includes green methodology i.e. no solvent usage for reaction which concomitantly exert cost reduction, minimization of operational time, optimum use of energy, avoid high evaporation losses, reduction in reactor occupancy time, and increase in batch size and yield improvement.
By taking in to account of overall prior arts the present invention provide the substantial advantages over prior arts process due to solvent free condition for synthesis of highly pure Metformin hydrochloride:
1. No hydrocarbon solvents such as xylene, toluene etc are used as per prior arts.
2. No use of water soluble solvents such as DMF, DMSO etc as per prior arts.
3. As the present invention is solvent free process, batch size can be increased upto a considerable level.
4. Environmental friendly green process technology.
5. Obtained metformin hydrochloride according to present invention is free flowing with a reduced particle size.
6. Scalable and consistent with simple operations.

7. Impurity levels are much lower than the conventional hydrocarbon process.
8. Process can be converted in to continuous process against conventional batch process.
9. Saves total working hours to l/3rd as compared to conventional method.

10. Huge energy saving as there is no solvent or water recovery is required.
11. Improved particle size to get rid of cacking problem.
EXAMPLES:
The following examples are presented to illustrate the working of the present invention with best mode, but are not limiting the scope of the individual embodiment presented.
Example-1: Synthesis of highly pure Metformin hydrochloride.
To a 1.0 L RBF was charged dimethyl amine hydrochloride (116 g) and dicyandiamide (100 g). Solids were heated to 120°C, both the solids were melts to form clear solution at 7 0-80°C. Molten reaction mass was maintained at 110-120°C for 2 hours and filtered to another reactor or crystallizer, reaction mass was further heated to 140-150°C for 3-5 hours till precipitation/ crystallization of metformin hydrochloride. Reaction mass was cooled to 50-60°C and about 130 ml of methanol was charged thereafter and reaction mass was stirred to obtained slurry maintaining temperature for 1 hour at 55-60°C, product was filtered and washed with methanol (50 ml).

The product thus obtained as wet solid was again charged in to the reactor and slurry with methanol (130 ml) at 55-60°C, reaction mass was cooled to ambient temperature. The product thus obtained was filtered washed with methanol (50 ml) and dried at 80-85°C for 8-10 hours. Yield:-187 g (94.6%) Purity: 99.96%
Example-2: Synthesis of highly pure Metformin hydrochloride.
To a 1.0 L RBF was charged Dimethyl amine hydrochloride (116 g) and dicyandiamide (100 g). Solids were heated to 120°C, both the solids were melts to form clear solution at 7 0-80°C. Molten reaction mass was maintained at 110-120°C for 2 hours and then further heated to 14 0-150 °C for 3-5 hours till precipitation/ crystallization of metformin hydrochloride. Reaction mass was cooled to 50-60°C and about 1000 • ml volumev of methanol was charged thereafter and reaction mass was stirred to obtained clear solution, clear solution was filtered to remove foreign particles. Filtered reaction mass was distilled atmospherically to remove 850-870 ml of methanol, to obtained slurry maintaining temperature for 1 hour at 55-60°C, product was filtered and washed with methanol (50 ml) . The product thus obtained as wet solid was again charged in to the reactor and slurry with methanol (130 ml) at 55-60°C, reaction mass was cooled to 25-30°C. The product thus obtained was filtered washed with methanol (50 ml) and dried at 80-85°C for 8-10 hours. Yield:-186 g (94.13%)

Purity: 99.98%
Example-3: Synthesis of highly pure Metformin hydrochloride.
To a 1.0 L RBF was charged Dimethyl amine hydrochloride (116 g) and dicyandiamide (100 g). Solids were heated to 120°C, both the solids were melts to form clear solution at 70-80°C. Molten reaction mass was maintained at 110-120°C for 2 hours and then further heated to 140-150°C for 3-5 hours till precipitation/ crystallization of metformin hydrochloride. Reaction mass was cooled to 90-100°C and about 200 .ml of water was charged thereafter and reaction mass was stirred to obtained clear solution, clear solution was filtered at 90-100°C to remove foreign particles. Filtered reaction mass was cooled to 5-10°C maintained for 1-2 hours at 5-10°C/ product was filtered and washed with methanol (100 ml) . The product thus obtained as wet solid was again charged in to the reactor and slurry with methanol (130 ml) at 55-60°C, reaction mass was cooled to ambient temperature. The product thus obtained was filtered washed with methanol (50 ml) and dried at 80-85°C for 8-10 hours. Yield:-178 g (90%) Purity: 99.94%
Example-4: Synthesis of highly pure Metformin hydrochloride.
To a 1.0 L RBF was charged Dimethyl amine hydrochloride (116 g) and dicyandiamide (50 g) . Solids were heated to 120 °C, both the solids were melts to form clear solution

at 70-80°C. Molten reaction mass was maintained at 110-12 0°C for 2 hours and then add dicyandiamide in one or more lots at regular intervals of 10 minutes (20g + lOg + lOg +10g) further reaction mass heated to 140-150°C for 3-5 hours till precipitation/ crystallization of metformin hydrochloride. Reaction mass was cooled to 50-60°C and about 1000 ml of methanol was charged thereafter and reaction mass was stirred to obtained clear solution, clear solution was filtered to remove foreign particles. Filtered reaction mass was distilled atmospherically to remove 870 ml of methanol, to obtained slurry maintaining temperature for 1 hour at 55-60°C, product was filtered and washed with methanol (50 ml). The product thus obtained as wet solid was again charged in to the reactor and slurry with methanol (130 ml) at 55-60°C, reaction mass was cooled to ambient temperature. The product thus obtained was filtered washed with methanol (50 ml) and dried at 80-85°C for 8-10 hours. Yield:-180 g Purity: 99.96%
Example-5: Synthesis of highly pure Metformin hydrochloride.
To a 1.0 L RBF was charged Dimethyl amine hydrochloride (116 g) and dicyandiamide (50 g) . Solids were heated to 120°C, both the solids were melts to form clear solution at 7 0-80°C. Molten reaction mass was maintained at 110-120°C for 2 hours and then heat the reaction mass at 135-14 0°C and then add dicyandiamide in one or more lots at regular intervals of 10 minutes (20g* + lOg + lOg +10g) ,

further reaction mass heated to 140-150°C for 3-5 hours till precipitation/crystallization of metformin hydrochloride. Reaction mass was cooled to 50-60°C and about 1000 ml of methanol was charged thereafter and reaction mass was stirred to obtained clear solution, clear solution was filtered to remove foreign particles. Filtered reaction mass was distilled atmospherically to remove 870 ml of methanol, to obtained slurry maintaining temperature for 1 hour at 55-60°C, product was filtered and washed with methanol (50 ml). The product thus obtained as wet solid was again charged in to the reactor and slurry with methanol (130 ml) at 55-60°C, reaction mass was cooled to ambient temperature. The product thus obtained was filtered washed with methanol (50 ml) and dried at 80-85°C for 8-10 hrs. Yield:-178.6 g Purity: 99.94%
Example-6: Synthesis of highly pure Metformin hydrochloride.
To a 1.0 L RBF was charged Dimethyl amine hydrochloride (116 g) and dicyandiamide (100 g). Solids were heated to 120-130 °C, both the solids were melts to form clear solution at 7 0-8 0°C. Molten reaction mass was maintained at 120-130°C for 4-6 hours till precipitation/ crystallization of metformin hydrochloride. Reaction mass was cooled to 50-60°C and about 200ml of methanol was charged, stirred the slurry maintaining temperature for 1 hour at 55-60°C, cool the reaction mass to 25-30°C/ product was filtered and washed with methanol (50 ml) .

The product thus obtained as wet solid was again charged in to the reactor and slurry with methanol (130 ml) at 55-60°C, reaction mass was cooled to ambient temperature. The product thus obtained was filtered washed with methanol (50 ml) and dried at 80-85°C for 8-10 hours. Yield:-130 g Purity: 99.90%

WE CLAIM:
1. An improved process for synthesis of highly pure
Metformin hydrochloride comprising the steps of:
a) treating dimethylamine hydrochloride and cyanoguanidine in solid form in to the reactor at 70-140°C without solvent;
b) the obtained molten mass of dimethylamine hydrochloride and' cyanoguanidine is filtered through Pharma filter aid at temperature 110-120°C;
c) heating the filtered molten reaction mass at 130-150°C by maintaining temperature for 3-5 hrs without vacuum or optionally with vacuum;
d) cooling the reaction mass at temperature 55-60°C and adding 1-2 volumes of methanol with maintaining reaction mass at 55-60°C;
e) further cooling the reaction mass obtained in step (d) at temperature 25-30°C and filtered or optionally repeat the steps (d) and (e) ;and
f) dry the obtained solid in step (e) at temperature 80-85 °C for 8-12 hrs to obtained highly pure metformin hydrochloride.

2. The highly pure Metformin hydrochloride obtained by the process according to claim 1.
3. The process according to claim 1, wherein the reaction of dimethyl amine hydrochloride with cyanoguanidine is carried out at a temperature in the range of 70°C to

160 °C for a period of 2 hours to 12 hours in solvent free condition.
4. The process according to claim 1, wherein the molar ratio of cyanoguanidine and dimethyl amine hydrochloride is 1.0 to 1.13-1.19 respectively, but more preferably 1.0 to 1.18.
5. The process according to claim 1, wherein • the cyanoguanidine is added in dimethyl amine hydrochloride either in one lot or optionally more than one lot.
6. The process according to claim 1, wherein after completion of the reaction, the resulting Metformin hydrochloride is further purified through solvent slurry.
7. The process according to claim 6, wherein suitable solvent used for solvent slurry is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol and the like or mixture(s) thereof.
8. The highly pure Metformin hydrochloride obtained by the process according to claim 1 having purity more than 99.9% and melamine content less than 0.0011%.
9. The highly pure Metformin hydrochloride obtained by the process according to claim 1 comprises:

a)Cyanoguanidine content less than 0.02%;
b)Dimethyl amine content less than 180 part per
million; c)(4,6-diamino-l,3,5-triazin-2-yl)guanidine content
less than 0.05%; d)Single unidentified impurity less than 0.05%.
10. The highly pure Metformin hydrochloride obtained by the process according to claim 1, wherein the highly pure Metformin hydrochloride exhibit anticacking property with particle size (D90) less than 200 \im.