Metformin Tablets
Action and use
Biguanide; treatment of diabetes mellitus.
Definition
Metformin Tablets contain Metformin Hydrochloride. They are coated.
Content of metformin hydrochloride, C4H11N5,HCl
95.0 to 105.0% of the stated amount.
Identification
Shake a quantity of the powdered tablets containing 20 mg of Metformin Hydrochloride with 20 mL of absolute ethanol, filter, evaporate the filtrate to dryness on a water bath and dry the residue at 105° for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of metformin hydrochloride (RS 217).
TESTS
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using as the medium 900 mL of a 0.68% w/v solution of potassium dihydrogen orthophosphate adjusted to pH 6.8 by the addition of 1m sodium hydroxide and rotating the basket at 100 revolutions per minute. Withdraw a sample of 10 mL of the medium. Filter, dilute 10 mL of the filtrate to 100 mL with water and dilute 10 mL of the resulting solution to 100 mL with water. Measure the absorbance of a layer of suitable thickness of the filtered sample, suitably diluted if necessary, at the maximum at 233 nm, Appendix II B. Calculate the total content of metformin hydrochloride, C4H11N5,HCl, in the medium taking 806 as the value of A (1%, 1 cm) at the maximum at 233 nm.
1-Cyanoguanidine
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.50 g of Metformin Hydrochloride with 100 mL of the mobile phase, filter and use the filtrate. For solution (2) dissolve 20 mg of 1-cyanoguanidine in water, dilute to 100 mL with water and dilute 1 mL of the resulting solution to 200 mL with the mobile phase.
The chromatographic procedure may be carried out using (a) a stainless steel column (12.5 cm × 4.6 mm) packed with a regular, porous silica gel to which benzene sulfonic acid groups have been chemically bonded (5 µm) (Partisphere 5 µ SCX is suitable), (b) a 1.7% w/v solution of ammonium dihydrogen orthophosphate adjusted to pH 3.0 with orthophosphoric acid as the mobile phase with a flow rate of 1 mL per minute and (c) a detection wavelength of 218 nm.
Inject 20 µL of solution (2). Adjust the sensitivity of the system so that the height of the principal peak in the chromatogram obtained is not less 50% of the full scale of the recorder.
Inject separately 20 µL of solutions (1) and (2). In the chromatogram obtained with solution (1) the area of any peak corresponding to 1-cyanoguanidine is not greater than the area of the peak in the chromatogram obtained with solution (2) (0.02%).
Assay
Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.1 g of Metformin Hydrochloride with 70 mL of water for 15 minutes, dilute to 100 mL with water and filter, discarding the first 20 mL. Dilute 10 mL of the filtrate to 100 mL with water and dilute 10 mL of the resulting solution to 100 mL with water. Measure the absorbance of the resulting solution at the maximum at 232 nm, Appendix II B. Calculate the content of the C4H11N5,HCl taking 798 as the value of A(1%, 1 cm) at the maximum at 232 nm.