June 1, 2023 by KBS.

Method for Analysis of Ivabradine hydrochloride with High-Performance Liquid Chromatographic

Testing the finished product of Ivabradine HCl tablets involves various quality control measures to ensure the safety, efficacy, and consistency of the medication. Method for Analysis of Ivabradine hydrochloride Tablet with High-Performance Liquid Chromatographic Here is a general overview of the testing procedure for Ivabradine HCl finished products:
Please note that this is a general outline of the testing procedure, and the specific requirements may vary depending on the country, regulatory guidelines, and the particular version of the monograph being followed. Always consult the relevant monographs, guidelines, and validated testing procedures for accurate and reliable testing of Ivabradine HCl finished products.

Table of Contents

PURPOSE:

To describe the procedure for analysis at the in-process and finished stage of the Ivabradine HCl Tablet.

SCOPE:

This SAP gives a detailed outline for the finished product analysis of the Ivabradine HCl Tablet and will cover in-process testing activities on a physical, chemical & instrumental basis.

RESPONSIBILITY:

QC Analyst is responsible for physical / chemical testing and preparing standard analytical procedure.

It is the responsibility of QC Manager to assist and ensure Testing Procedure as per SAP and to make certain that this SAP is followed in its entirety, reviewed regularly and revised as necessary.

REFERENCE:

INNOVATORS SPECIFICATIONS

MATERIAL AND EQIUPMENT:

UV Spectrophotometer
HPLC
Dissolution apparatus
Friability apparatus
Hardness apparatus
Disintegration Tester
Vernier Caliper
Analytical Balance
Moisture analyzer
Mortar and pestle
Spatula
Filter Paper
Magnetic Stirrer & Hot Plate
Sonicator
Vacuum Pump
Glassware
Water

PROCEDURE:

FINAL MIX

Method for Analysis of Ivabradine hydrochloride Tablet with High-Performance Liquid Chromatographic

Description:

A white powder.

Procedure: Take 2.0 g of the test sample in a watch glass and observe visually with black background. Check the appearance of color, nature and any visible foreign particles.

Identification:

The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Loss on Drying: (By Moisture Analyzer)

Procedure:

Turn on instrument 20 minute before the test. Take 2 g powder spread uniformly on Moisture Analyzer plate. Close the lid and press start button.

NMT 3.0% when determined by LOD Apparatus, Use 2.0 g of powder.

Assay: (Limit: 90%-110%)

Procedure:

Diluent: Water

Standard Solution:

Take 27 mg of Ivabradine HCl WS equivalent to 25 mg of Ivabradine dissolved in water and make up the volume to 50mL with water. Shake, and sonicate for 5 minutes to facilitate dissolution.

Take 2 mL from standard stock solution and make up the volume to 50 mL with water.

Sample solution:

Take compression weight of finally grinded granules equivalent to 25 mg of Ivabradine HCl dissolve it in 60mL water and sonicate for 6 minutes make volume up to 100 mL with water, filter. Shake by mechanical means for 4 minutes to disperse and allow any insoluble matter to settle. Sonicate for 10 minutes.

Pass a portion of the sample through a suitable filter of 0.45um pore size.

Take 2 mL from filtrate and make up the volume to 25 mL with water.

Take reading at UV spectrophotometer at 286 nm using water blank.

Calculations:

Sample Absorbance x Standard Concentration x Ave. Weight of Tablet x Potency

Standard Absorbance x Sample Concentration x Label Claim x Factor

Limit: Ivabradine as HCl: 90%-110%of the labeled amount

Hardness Test

Perform the hardness test on 10 tablets and take the average. Power on the instrument and regulate zero adjustment and preset the ‘’HARDNESS’’. Place the tablet on the test plate, begin testing and read the hardness thickness and diameter. Clean the shattered tablet and print out test results, perform the test on 10 tablets and take the average.

Hardness Standard Limit: Not more than 10.00 Kg

Friability Test:

For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets corresponding to 6.5 g. For tablets with a unit mass of more than 650 mg, take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before, and accurately weigh. Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablet sample after tumbling, the sample fails the test. If the results are doubtful or if the weight loss is greater than the targeted value, the test should be repeated twice and the mean of the three tests determined. A maximum mean weight loss from the three samples of not more than 1.0% is considered acceptable for most products.

% FRIABILITY= W1-W2 x 100/W1

Disintegration Test:

Place the beaker filled with water into the beaker stand inside the bath and. Switch on the instrument, set the temperature at 37ºC± 2º C and wait till the temperature of the beaker reaches to the 37ºC± 2º C. Engage the basket on basket hook put the tablets in 6 tubes individually and place the discs then start the oscillations and timer. Note the disintegration time of all the six tablets.

Note the Disintegration time of 1st tablet to the last tablet.

Disintegration Time: NMT 15 minutes at 370C ± 20C

Acceptance criteria of disintegration for tablets:

If 1 or 2 tablets fail to disintegrate completely repeat the test on 12 additional tablets, not less than 16 of the totals of 18 tablets tested disintegrate completely.

Dissolution Test:

USP Apparatus: USP Apparatus II Peddle

Medium: 900mL water

Speed: 50 rpm

Time: 15 Minutes

Medium Temperature: 37ºC ± 0.5ºC

Diluent: Dissolution medium

Standard stock solution: Take 27 mg of Ivabradine HCl equivalent to 25mg of Ivabradine in 100 mL volumetric flask and dissolved in water Shake, and sonicate for 3 minutes to facilitate dissolution.

Standard solution: Transfer the 2mL of stock solution to 100mL volumetric flask in water. Pass through a suitable filter.

Sample solution: Pass a portion of solution under through a suitable filter of 0.45-um pore size.

Instrumental Conditions

Mode: UV

Analytical wavelength: UV 286 nm

Blank: Medium

Calculations:

Sample Absorbance x Standard Concentration x Potency

Standard Absorbance x Sample Concentration

Tolerance:

The amount of drug dissolve in solution for each tablet is not less Than 80% of the amount stated on the label for Ivabradine at 15 minutes.

Acceptance criteria

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 less than Q – 15%.
S3	12	Average of 24 units (S1 ± S2 ± S3) is equal to or greater than Q, not more than 2 units are less than Q– 15%, and no unit is less than Q – 30%.

BLISTER STAGE:

Leak Test:

Take 06 blisters of tablet 03 filled and 03 empty. Dip these blisters in the bowl of leak test apparatus containing colored water. Create vacuum 250 mmHg and hold for one minute. Release vacuum and check the penetration of water inside the blisters. All blisters should be free of water.

CONTENT UNIFORMITY TEST:

Diluent: Same as for assay

Standard Solution:

Same as for assay

Sample solution: Take 10 tablets and dissolved individually each tablet in 25 mL volumetric flask and dissolved in diluent. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.

Transfer the 2mL of stock solution to 20 mL volumetric flask and make up volume with Diluent.

Pass through a membrane filter of 0.45-µm pore size.

Calculations: