Procedure for Dissolution of Glimepiride + Metformin Tablets

GLIMEPIRIDE 4 mg + METFORMIN 850 mg TABLETS

Dissolution

For Glimepiride Content:

Dissolution parameter:

Preparation of 0.5% w/v Sodium Lauryl Sulfate: Dissolve about 5 g of Sodium Lauryl Sulfate in 1000 ml of water.

Medium: 0.5% w/v Sodium Lauryl Sulfate, 500 ml.

Apparatus: Paddle.                     

Speed: 100 rpm.

Run Time: 60 minutes.

Dissolution procedure:

  1. Set dissolution apparatus by programming temperature, rotation and run time at 37°C±0.5°C, 

100 rpm and 60 minutes respectively.

  • Place 500 ml of dissolution medium into each of the six vessels of the dissolution apparatus.
  • Assemble the apparatus and equilibrate the dissolution medium at 37°C±0.5°C.
  • Place one tablet into each of six vessels and allow the tablet to the bottom of the vessels

      before starting the rotation of the paddles.

  • Immediately start the rotation of the paddles at the speed of 100 rpm for 60 minutes.

                                      Note: Keep the vessel covered during the test.

  • After 60 minutes, withdraw the 10 ml aliquots from a zone midway between the surface of the

      dissolution medium and top of the paddles, from each of six vessels.

Preparation of 0.1 M Methanolic sodium Hydroxide: Prepare a solution of 4 g of sodium hydroxide in 30 ml of distilled water. Sonicate to dissolve. Cool, add this solution slowly with constant stirring to 970 ml of methanol, if the above solution is not clear then filter through 0.45 micron membrane filter.

Preparation of standard solution: Weigh accurately about 40 mg of Glimepiride and transfer into a 200 ml volumetric flask. Add about 140 ml of 0.1 M Methanolic sodium hydroxide and sonicate to dissolve. Equilibrate to room temperature and dilute to volume with 0.1 M Methanolic sodium hydroxide and filter.

Pipette 2 ml of the filter solution into a 50 ml volumetric flask and make up the volume to 50 ml with dissolution medium.

Preparation of sample solution: Withdraw about 10 ml of aliquot of each specimen from a zone midway between the surface of the dissolution medium and top of the rotating paddle, not less than 1 cm from the vessel wall and filter through Whatman filter paper No. 1 or suitable.

Buffer solution: Dilute 13.8 g of sodium dihydrogen phosphate to 1000 ml of water. Adjust pH to 6.0 with 2 M sodium hydroxide solution.

Mobile phase preparation: Filtered and degassed mixture of Buffer: Methanol (30:70).

Chromatographic conditions:

Column: A stainless steel column 25 cm x 4.6 mm packed with octadecylsilane bonded to porous silica (5 µm).

Column temperature: 25°C.

Flow rate: 1.5 ml per minute.

Detection wavelength: 220 nm.

Injection volume: 50 µl.

Mode: Isocratic

Syringe rinse diluent: Methanol (50%). Dilute 50 ml of Methanol to 100 ml with water.

Blank: Methanol.

Procedure: Separately inject equal volumes (about 50 µl) of the blank, five replicate injections of standard solution and the test solution, record the chromatograms and measure the responses for the analyte peaks.

System suitability: The test is not valid unless the column efficiency is not less than 2000 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0%.

Interpretation: The requirements are met if the quantities of active ingredient dissolved from the pooled sample conform to the accompanying acceptance table for a pooled sample. Continue testing through the three stages unless the results conform at either S1 or S2.

Acceptance Table

Stage Number Tested Acceptance Criteria
S1 6 Each unit is not less than Q+5%.  
S2 6 Average of 12 units (S1+S2) is equal to or greater than Q and no unit is less than Q-15%.  
S3 12 Average of 24 units (S1+S2+S3) Equal to or greater than Q, not More than 2 units are less than Q-15% and no unit is less than Q-25%.

Calculation: Calculate the content of Glimepiride (C24H34N4O5S) in percent, by using given below formula:

          Test   area                  Std. dilution            Potency (in %)

——————————–x ———————-x ————————– x 100            

   Average area of Std.         Test dilution                  100

For Metformin Hydrochloride Content:

Dissolution parameter:

Medium: 0.1 M Hydrochloric Acid, 900 ml.

Apparatus: Paddle.                     

Speed: 50 rpm.

Run Time: 8 Hours (after 1, 2, 4 and 8 Hours)  

Dissolution procedure:

  1. Set dissolution apparatus by programming temperature, rotation and run time at 37°C±0.5°C, 

50 rpm and 8 hours respectively.

  • Place 900 ml of dissolution medium into each of the six vessels of the dissolution apparatus.
  • Assemble the apparatus and equilibrate the dissolution medium at 37°C±0.5°C.
  • Place one tablet into each of six vessels and allow the tablet to the bottom of the vessels

      before starting the rotation of the paddles.

  • Immediately start the rotation of the paddles at the speed of 50 rpm for 8 hours.

                                      Note: Keep the vessel covered during the test.

  • After 1, 2, 4 and 8 hours, withdraw the 10 ml aliquots from a zone midway between the surface of the dissolution medium and top of the paddles, from each of six vessels.

Preparation of standard solution: Weigh accurately about 48 mg of Metformin Hydrochloride WS and transfer into a 100 ml volumetric flask. Add about 70 ml of dissolution medium and sonicate to dissolve and dilute to 100 ml with dissolution medium and filter.

Pipette 5 ml of the filter solution into a 50 ml volumetric flask and make up the volume to 50 ml with mobile phase.

Preparation of sample solution: At the end of specified time intervals, withdraw about 10 ml of aliquot of each specimen from a zone midway between the surface of the dissolution medium and top of the rotating paddle, not less than 1 cm from the vessel wall and filter through Whatman filter paper No. 1 or suitable.

Pipette 5 ml of the filter solution into a 100 ml volumetric flask and make up the volume to 100 ml with mobile phase.

Buffer solution: Mixture of 0.087% w/v sodium pentane sulphonic acid and 0.12% w/v of sodium chloride. (Dissolve about 870 mg of sodium pentane sulphonate and 1.2 g of sodium chloride in 1000 ml of water). Adjust the pH to 3.5 ± 0.05 with 1% v/v orthophosphoric acid.

Mobile phase preparation: Prepare filtered and degassed mixture of Buffer and Methanol in the ratio of (90:10).

Chromatographic conditions:

Column: A stainless steel column 25 cm x 4.6 mm packed with octadecylsilane bonded to porous silica (5 µm).

Flow rate: 1.0 ml per minute.

Detection wavelength: 233 nm.

Injection volume: 10 µl.

Mode: Isocratic

Syringe rinse diluent: Water: Methanol (90: 10).

Blank: Mobile phase.

Procedure: Separately inject equal volumes (about 10 µl) of the blank, five replicate injections of standard solution and the test solution in duplicate, record the chromatograms and measure the responses for the analyte peaks.

System suitability: The test is not valid unless the column efficiency is not less than 2000 theoretical plates, the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0%.

Acceptance Criteria: The requirements are met if the quantities of active ingredient dissolved from the dosage units tested conform to the accompanying acceptance table. Continue testing through the 3 stages unless the results conform at earlier level.

Calculation: Calculate the content of Metformin Hydrochloride (C4H11N5, HCl) in percent, by using given below formula:

          Test   area                     Std. dilution            Potency (in %)

——————————–x ———————-x ————————– x 100            

   Average area of Std.            Test dilution                  100

Bhanu Pratap Singh

BHANU PRATAP SINGH IS EXPERIENCED IN PHARMACEUTICAL, AUTHOR AND FOUNDER OF PHARMACEUTICAL GUIDESLINE (WWW.PHARMAGUIDESLINE.COM), A WIDELY READ PHARMACEUTICAL BLOG SINCE 2019. EMAIL:- INFO@PHARMAGUIDESLINE.COM

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