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An Improved Process For The Synthesis Of Extremely Pure Metformin Hydrochloride Substantially Free From Melamine And Cyanoguanidine

Abstract: Disclosed herein is a process for the preparation of highly pure Metformin hydrochloride, which is substantially free from melamine and Cyanoguanidine impurities using double crystallization technique.

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Patent Information

Application #
Filing Date
13 July 2007
Publication Number
13/2009
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
Parent Application

Applicants

WANBURY LIMITED
B-WING, 10TH FLOOR, BSEL TECH PARK, SECTOR 30 A, PLOT NO. 39/5 & 39/5A, OPP.VASHI RAILWAY STATION, NAVI MUMBAI.

Inventors

1. SANGANABHATLA, SHANKAR
402, PLOT NO.51, SECTOR-12 B, KHOPARKHAIRANE, NAVI MUMBAI-400709
2. RANADE, PRASAD VASUDEO
27, BAZAR PETH, RAJAPUR-416702 DIST. RATNAGIRI
3. SURYAVANSHI, JITENDRA PANDURANG
N.A. 16, B.M.C. COLONY, KHARDEO NAGAR, CHEMBUR (E), MUMBAI-400071

Specification

FORM 2 THE PATENT ACT 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rulel3) 1. TITLE OF THE INVENTION: " An improved process for the synthesis of extremely pure metformin hydrochloride substantially free from melamine and Cyanoguanidine" 2. APPLICANT (S) (a) NAME: WANBURY LIMITED (b) NATIONALITY: Indian Company incorporated under the Indian Companies Act, 1956 (c) ADDRESS: B- Wing, 10th Floor, BSEL Tech Park, Sector 30 A, Plot No. 39/5 & 39/5A, Opp. Vashi Railway Station, Navi- Mumbai- 400 703, Maharashtra, India 3. PREAMBLE TO THE DESCRIPTION The following specification particularly describes the invention and the manner in which it is to be performed. Technical field: The present invention relates to process for the preparation of highly pure Metformin hydrochloride, which is substantially free from melamine and Cyanoguanidine impurities using double crystallization technique. Background and prior art: 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(R) tablets by Bristol-Myers Squibb Co. Each GLUCOPHAGE(R) 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(R). Dosage of GLUCOPHAGE(R) 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 a molecular formula C4H11N5. HCL and molecular wt 65.63. Metformin HCL is freely soluble in water and practically insoluble in acetone, ether and chloroform. US 3174901 disclose composition containing dimethyl biguanide used in the form of hydrochloride salt wherein it is used for treating diabetes by oral administration. (Merck index details). Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide hydrochloride) of formula I is a member of the biguanide class of oral antihyperglycemics which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. 2 NH H,C N^NH^NH2-HCI "go N y II || HCI J H2N^NH NH NH Uh3 2 n m Metformin is commercially manufactured by condensation of dimethyl amine (Formula II) in the form of hydrochloride and Dicyanodiamide, also called as Cyanoguanidine (Formula III) as shown in scheme I. (Scheme-1) NH H2N^NH" ' Y if 3 NH NH Scheme-1 HcNH + ...A...

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