There are different methods available for Amlodipine Besylate and Olmesartan Medoxomil Tablet Testing Method, but here is a general overview of some common analytical methods:
HPLC Method: High-Performance Liquid Chromatography (HPLC) is a widely used analytical method for the quantification of Amlodipine Besylate and Olmesartan Medoxomil in tablets. In this method, a liquid sample is passed through a column packed with stationary phase materials, and the components are separated based on their chemical and physical properties. The separated components are detected using a UV detector, and the amount of each component is calculated.
Spectroscopic Method: UV-Visible spectrophotometry is a simple and cost-effective method for the quantitative analysis of Amlodipine Besylate and Olmesartan Medoxomil in tablets. In this method, a known amount of the drug is dissolved in a solvent, and the absorbance is measured at a specific wavelength. The amount of drug is calculated using the Beer-Lambert law.
These methods are just a few examples, and there may be other methods available depending on the specific requirements and regulations of the country or region. It’s important to note that the testing method should be validated to ensure accuracy, precision, and reproducibility.
PURPOSE:
To describe the procedure for analysis at in-process and finished stage of Amlodipine Besylate and Olmesartan Medoxomil 5/20mg Tablet.
SCOPE:
This SAP gives detailed outline for the finished product analysis of Amlodipine Besylate and Olmesartan Medoxomil 5/20mgTabletand will cover In process testing activities on 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:
USP 43, NF 38
MATERIAL AND EQIUPMENT:
- HPLC
- Dissolution apparatus
- Friability apparatus
- Hardness apparatus
- Disintegration Tester
- Vernier Caliper
- Analytical Balance
- pH meter
- Moisture analyzer
- Mortar and pestle
- Spatula
- Filter Paper
- Magnetic Stirrer & Hot Plate
- Sonicator
- Vacuum Pump
- Glassware Ammonium Acetate
- Triethylamine
- Acetonitrile HPLC Grade
- Methanol HPLC Grade
- Distilled water
PROCEDURE:
FINAL MIX
Amlodipine Besylate and Olmesartan Medoxomil Tablet Testing Method
Description:
A white to off 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: (By HPLC)
A- The UV spectra of the amlodipine and Olmesartan medoxomil peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.
B- The retention times of the amlodipine and Olmesartan medoxomil peaks of the Sample solution correspond to those 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%)Compression Weight of Powder/Tablet:
Procedure:
Solution A:
6.9 g/L of sodium phosphate, monobasic. Adjust with phosphoric acid to a pH of 2.5.
Solution B: Acetonitrile
Mobile phase: See Table 1.
Diluent: Acetonitrile and water (50:50)
Standard stock solution: 0.28 mg/mL of USP AmlodipineBesylate RS and 0.8 mg/mL of USP Olmesartan Medoxomil RS in Diluent
Standard solution: 0.056 mg/mL of USP Amlodipine Besylate RS and 0.16 mg/mL of USP Olmesartan Medoxomil RS in Diluent from Standard stock solution
Sample stock solution: Nominal concentrations given inTable 2 are prepared as follows.
For Tablet strength 5/20, transfer NLT 5 Tablets equivalentto 25 mg of amlodipine and 100 mg of Olmesartan medoxomil into a suitable volumetric flask. Add water to20% of the total volume and sonicate for 5 min. Addacetonitrile to 20% of the total volume and sonicate for5 min. Add Diluent to 30% of the total volume andsonicate for 15 min. Dilute with Diluent to volume.
Centrifuge a portion of the solution for 10 min and passthrough a filter of 0.45-μm pore size.
For Tablet strength 5/40, 10/20, or 10/40, transfer NLT 5 Tablets equivalent to 25 mg of amlodipine and 200 mg of olmesartan medoxomil, 50 mg of amlodipine and 100 mg of olmesartan medoxomil, or 50 mg of amlodipine and 200 mg of olmesartan medoxomil in to a suitable volumetric flask. Add water to 10% of the total volume and sonicate for 5 min. Add acetonitrile to 10%of the total volume and sonicate for 5 min. Add Diluent to 30% of the total volume and sonicate for 15 min. Dilute with Diluent to volume. Centrifuge a portion of the solution for 10 min and pass through a filter of 0.45-μmpore size.
Table 1:
| Time (Min) | Solution A (%) | Solution B (%) |
| 0 | 68 | 32 |
| 12 | 68 | 32 |
| 15 | 30 | 70 |
| 21 | 30 | 70 |
| 23 | 68 | 32 |
| 25 | 68 | 32 |
Table 2
Sample solution: Nominal concentrations in Diluent from Sample stock solution are given in Table
| Tablet Strength Amlodipine/Olmesartan Medoxomil (mg/mg) | Nominal Concentration of Amlodipine (mg/ml) | Nominal Concentration of Olmesartan Medoxomil (mg/ml) |
| 5/20, 10/40 | 0.5 | 2 |
| 5/40 | 0.25 | 2 |
| 10/20 | 0.5 | 2 |
Table 3
Sample solution: Nominal concentrations in Diluent from Sample stock solution are given in Table
| Tablet Strength Amlodipine/Olmesartan Medoxomil (mg/mg) | Nominal Concentration of Amlodipine (mg/ml) | Nominal Concentration of Olmesartan Medoxomil (mg/ml) |
| 5/20, 10/40 | 0.04 | 0.16 |
| 5/40 | 0.02 | 0.16 |
| 10/20 | 0.04 | 0.08 |
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 254 nm. For Identification A, use a diode array detector in the range of 200–400 nm.
Column: 4.6-mm × 25-cm; 5-μm packing L11Temperatures
Autosampler: 5°
Column: 60°
Flow rate: 2 mL/min
Injection volume: 10 μL
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0 for amlodipine and Olmesartan medoxomil peaks
Relative standard deviation: NMT 2.0% for amlodipineand olmesartan medoxomil peaks
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of amlodipine (C20H25ClN2O5) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
rU= peak response of amlodipine from the Sample solution
rS= peak response of amlodipine from the Standardsolution
CS = concentration of USP Amlodipine Besylate RS inthe Standard solution (mg/mL)
CU = nominal concentration of amlodipine in theSample solution (mg/mL)
Mr1 = molecular weight of amlodipine, 408.88
Mr2 = molecular weight of amlodipine besylate, 567.05
Calculate the percentage of the labeled amount of olmesartan medoxomil (C29H30N6O6) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU= peak response of olmesartan medoxomil from theSample solution
rS= peak response of olmesartan medoxomil from the Standard solution
CS = concentration of USP Olmesartan Medoxomil RS in the Standard solution (mg/mL)
CU = nominal concentration of olmesartan medoxomilin the Sample solution (mg/mL)
Acceptance criteria
Amlodipine: 90.0%–110.0%
Olmesartan medoxomil: 90.0%–110.0%
IMPURITIES
ORGANIC IMPURITIES
Solution A, Solution B, Mobile phase, Diluent, Standard stock solution, Sample stock solution, and
Chromatographic system: Proceed as directed in the Assay.
Standard stock solution A: 28 μg/mL of USP Amlodipine Besylate RS and 80 μg/mL of USP Olmesartan Medoxomil RS in Diluent from Standard
stock solution
Standard stock solution B: 50 μg/mL of USP Amlodipine Related Compound A RS in Diluent
Standard solution: 1.4 μg/mL of USP Amlodipine Besylate RS, 2.5 μg/mL of USP Amlodipine RelatedCompound A RS, and 4 μg/mL of USP Olmesartan Medoxomil RS in Diluent from Standard stock solution A andStandard stock solution B
Sensitivity solution: 0.28 μg/mL of USP Amlodipine Besylate RS, 0.5 μg/mL of USP Amlodipine RelatedCompound A RS, and 0.8 μg/mL of USP Olmesartan Medoxomil RS in Diluent from Standard solution
Sample solution: Use the Sample stock solution, prepared asdirected in the Assay.
System suitability
Samples: Standard solution and Sensitivity solution
[NOTE—See ▲Table 7▲ (RB 1-Apr-2021) for relative retention times.]
Suitability requirements
Tailing factor: NMT 2.0 for amlodipine related compound A, amlodipine, and olmesartan medoxomilpeaks, Standard solution
Relative standard deviation: NMT 5.0% for amlodipine related compound A, amlodipine, and Olmesartan medoxomil peaks, Standard solution Signal-to-noise ratio: NLT 10 for amlodipine related compound A, amlodipine, and olmesartan medoxomilpeaks, Sensitivity solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of amlodipine related compound A free base in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
rU= peak response of amlodipine related compound Afrom the Sample solution
rS= peak response of amlodipine related compound Afrom the Standard solution
CS = concentration of USP Amlodipine RelatedCompound A RS in the Standard solution(mg/mL)
CU = nominal concentration of amlodipine in theSample solution (mg/mL)
Mr1 = molecular weight of amlodipine relatedcompound A free base, 406.86
Mr2 = molecular weight of amlodipine relatedcompound A, 522.94 Calculate the percentage of any unspecified amlodipinerelated impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
rU= peak response of any unspecified amlodipinerelated impurity from the Sample solution
rS= peak response of amlodipine from the Standardsolution
CS = concentration of USP Amlodipine Besylate RS inthe Standard solution (mg/mL)
CU = nominal concentration of amlodipine in theSample solution (mg/mL)
Mr1 = molecular weight of amlodipine, 408.88
Mr2 = molecular weight of amlodipine besylate, 567.05
Calculate the percentage of olmesartan or any un specified olmesartan medoxomil related impurity in the portion ofTablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU= peak response of olmesartan or any un specified olmesartan medoxomil related impurity from theSample solution
rS= peak response of olmesartanmedoxomil from theStandard solution
CS = concentration of USP Olmesartan Medoxomil RS in the Standard solution (mg/mL)
CU = nominal concentration of olmesartan medoxomilin the Sample solution (mg/mL)
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 tablet fail to disintegrate completely repeat the test on 12 additional tablets, not less than 16 of the total of 18 tablets tested disintegrate completely.
Hardness Test & Dimensions:
Perform the hardness test on 10 tablets and take the average. Power on the instrument and regulate zero adjustment and preset the ‘’HARDNESS’’ and “Thickness” mode. 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.
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/W1 x 100
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: By Weight variation
Calculation of Acceptance Value (AV):
Limits:
L1= ≤ 15 (For 10 Unit)
L2= ≤ 25 (For 30 Unit)
General Formula = M-x̄ ±ks
Acceptability Constant = (k)
Standard Deviation (SD) = s
Number of Units = (n)
Reference Value = M
Mean of Individual Content = x̄