In terms of testing, Ranolazine XR 500mg Tablet has undergone various clinical trials to establish its safety and efficacy. SOP for Ranolazine XR Tablet Testing HPLC and UV Method clinical trials have been conducted on a large number of patients with chronic angina, and the results have been published in peer-reviewed medical journals.
The clinical trials have demonstrated that Ranolazine XR 500mg Tablet is effective in reducing the frequency of angina episodes, improving exercise tolerance, and improving the quality of life in patients with chronic angina. The medication has also been found to be safe, with no significant side effects observed in most patients.
PURPOSE:
To describe the procedure for analysis at in-process and finished stage of Ranolazine XR 500mgTablet.
SCOPE:
This SAP gives detailed outline for the finished product analysis of Ranolazine XR 500mgTabletand 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:
INNOVATORS SPECIFICATIONS
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
- Methanol HPLC Grade
- Hydrochloric acid
- Distilled water
PROCEDURE:
FINAL MIX
Description:
White powder.
Procedure: Take 2.0 g of the test sample in a watch glass and observe visually with black backgoblong. Check the appearance of color, nature and any visible foreign particles.
Identification:
The UV (190-400 nm) spectrum of the 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%)Compression Weight of Powder/Tablet: 850 mg /tablet
Procedure:
Standard Solution:
Take 62.5 mg of Ranolazine WS dissolved in methanol and make up the volume to 25mL with methanol. 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 0.1N HCl.
Sample solution:
Take weight of finally grinded granules equivalent to 125 mg of Ranolazine and dissolved in methanol and make up the volume to 50mL with methanol. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.
Pass a portion of the sample stock solution through a suitable filter of 0.45um pore size.
Transfer the 2 mL of filtrate to a 50mL volumetric flask make up volume with 0.1N HCl. Take reading at UV spectrophotometer at 272 nm using 0.1N HClas blank.
Calculations:
Sample Absorbance x Standard Concentration x Ave. Weight of Tablet x Potency
Standard Absorbance xSample Concentration x Label Claim
(Limit for Ranolazine: 90%-110%of the labeled amount)
Dissolution Test:
Dissolution Medium:
- USP Apparatus: USP Apparatus II Paddle
- Medium: 0.1 N HCl
- Speed: 50rpm
- Volume: 900mL
- Recommended Sampling Time: Times: 1, 4, 12, and 24 h
- Diluent: Methanol : Water 1 : 1
Standard solution: Take 27.8 mg of Ranolazine WS dissolved in medium and make up the volume to 50mL with diluent. Shake, and sonicate for 5 minutes to facilitate dissolution
Take 5 mL from standard stock solution and make up the volume to 25 mL with medium.
Analysis: Pass portions of the solution under test through a suitable filter.
Dilute 5mL to 25 mL with Medium.
Instrumental Conditions
- Mode: UV
- Analytical wavelength: UV 271 nm
- Cell length: 10 mm
- Blank: Medium
Calculations:
Calculate the amount of Ranolazine dissolved by the formulae
Result = (Au/As) x Cs x V x D x (1/L) X 100.
Where,
Au= Absorbance of sample
As = Absorbance of WS
Cs= concentration in mg/ml of the working standard solution.
V = volume in ml of medium (900mL)
D = dilution factor of the sample solution
L = label claim (mg/Tablet).
Tolerance:
| Time in hours | Amount Dissolved |
| 1 | 15%-35% |
| 4 | 40%-60% |
| 12 | 65%-85% |
| 24 | NLT 85% |
The percentages of the labeled amount of Ranolazine dissolved at the times specified conform to Acceptance Table 2)
Uniformity of Dosage Units: (By Weight Variation)
Weigh 20 tablets individually and calculate the average weight as:
Average weight = (Weight Of 20 Tablets)/20
Weigh all these tablets individually and mark among these weights maximum (WMax) & minimum (WMin) weight tablets. Calculate the maximum and minimum variation in percent as:
Maximum% age variation =((WMax) – (WAvg.))/WAvg×100
Minimum % age variation ((WMin) – (WAvg.))/WAvg×100
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
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.
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