Action and use
Inhibition of ATP-dependent potassium channels (sulfonylurea); treatment of diabetes mellitus.
Definition
Glibenclamide Tablets contain Glibenclamide.
Production
The dissolution test below is carried out to demonstrate the appropriate release of Glibenclamide subject to approval from the competent authority.
Prepare a mixture containing 0.8134% w/v of anhydrous disodium hydrogen phosphate and 0.1350% w/v of potassium dihydrogen orthophosphate (solution A).
Carry out the dissolution test for tablets and capsules, Appendix XII B1. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
test conditions
(a) Use Apparatus 2 rotating the paddle at 100 revolutions per minute.
(b) Use 900 mL of solution A at a temperature of 37° as the medium.
procedure
(1) Withdraw 10 mL of the medium, filter (Minisart GS 25mm filters are suitable) and use the filtrate, discarding the first 5 mL of the filtrate.
(2) Dissolve
glibenclamide BPCRS in the minimum quantity of
methanol and dilute to an appropriate concentration with solution A.
chromatographic conditions
(b) Use isocratic elution using the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 225 nm.
(f) Inject 20 µL of each solution.
mobile phase
40 volumes of 0.1m potassium dihydrogen orthophosphate previously adjusted to pH 3.0 with orthophosphoric acid and 60 volumes of acetonitrile.
determination of content
Calculate the total content of glibenclamide, C23H28ClN3O5S, in the medium from the chromatograms obtained and using the declared content of C23H28ClN3O5S in glibenclamide BPCRS.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of glibenclamide, C23H28ClN3O5S
95.0 to 105.0% of the stated amount.
Identification
A. In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as that of the principal peak in the chromatogram obtained with solution (2).
B. In the test for Related substances, the principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (4).
Tests
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Extract a quantity of the powdered tablets containing 20 mg of Glibenclamide with four 5-mL quantities of a mixture of 10 volumes of
acetone and 20 volumes of
dichloromethane, evaporate the combined extracts to dryness at a temperature not exceeding 40° at a pressure of 2 kPa and dissolve the residue in 4 mL of a mixture of equal volumes of
chloroform and
methanol.
(3) 0.0020% w/v of
methyl N-
4-[2-(5-chloro-2-methoxybenzamido)ethyl]benzenesulfonylcarbamate BPCRS in a mixture of equal volumes of
chloroform and
methanol.
(4) 0.5% w/v of
glibenclamide BPCRS in a mixture of equal volumes of
chloroform and
methanol.
chromatographic conditions
(b) Use the mobile phase described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
mobile phase
5 volumes of ethanol (96%), 5 volumes of glacial acetic acid, 45 volumes of chloroform and 45 volumes of cyclohexane.
limits
In the chromatogram obtained with solution (1);
any spots corresponding to 4-[2-(5-chloro-2-methoxybenzamido)ethyl]benzenesulfonamide and methyl N-4-[2-(5-chloro-2-methoxybenzamido)ethyl]benzenesulfonylcarbamate are not more intense than the spots in the chromatograms obtained with solutions (2)(2.4%) and (3)(0.4%) respectively.
Uniformity of content
Tablets containing 5 mg or less of Glibenclamide comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Powder one tablet, add a mixture of 2 mL of
water and 20 mL of
methanol, mix with the aid of ultrasound until fully dispersed and filter through a 0.2-µm membrane filter (Anatop LC is suitable).
(2) Add 2 mL of
water to 20 mL of a 0.025% w/v solution of
glibenclamide BPCRS in
methanol, mix with the aid of ultrasound until fully dispersed and filter (0.2-µm Anatop LC is suitable).
chromatographic conditions
The chromatographic conditions described under Assay may be used.
determination of content
Calculate the content of C23H28ClN3O5S in each tablet using the declared content of C23H28ClN3O5S in glibenclamide BPCRS.
Assay
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix, with the aid of ultrasound, a quantity of the powdered tablets containing 5 mg of Glibenclamide with a mixture of 2 mL of
water and 20 mL of
methanol until fully dispersed and filter through a 0.2-µm membrane filter (Anatop LC is suitable).
(2) Dissolve 50 mg of
glibenclamide BPCRS in 10 mL of
methanol with the aid of ultrasound for 20 minutes, add sufficient
methanol to produce 50 mL and dilute 1 volume of this solution to 4 volumes with
methanol. To 20 mL of this solution add 2 mL of
water and mix.
chromatographic conditions
(b) Use isocratic elution using the mobile phase below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 300 nm.
(f) Inject 20 µL of each solution.
mobile phase
47 volumes of acetonitrile and 53 volumes of a 1.36% w/v solution of potassium dihydrogen orthophosphate previously adjusted to pH 3.0 with orthophosphoric acid.
determination of content
Calculate the content of C23H28ClN3O5S in the tablets using the declared content of C23H28ClN3O5S in glibenclamide BPCRS.