Throughout both the in-process and finished stages, these analyses help ensure the quality, safety, and efficacy of Tizanidine Hydrochloride Tablets, meeting regulatory requirements and providing reliable treatment for patients. A simple HPLC method for determination of Tizanidine hydrochloride in pharmaceutical preparations It’s important to note that specific testing protocols may vary based on regulatory guidelines and the manufacturer’s quality control procedures.
Analyzing the in-process and finished stages of Tizanidine Hydrochloride Tablets involves evaluating various aspects of the manufacturing process and the final product. Tizanidine Hydrochloride is a medication primarily used to treat muscle spasms and is commonly formulated into tablet dosage forms. Here’s an overview of what the analysis might entail:
PURPOSE:
To describe the procedure for analysis at the in-process and finished stage of the Tizanidine Hydrochloride Tablet.
SCOPE:
This SAP gives a detailed outline for the finished product analysis of the Tizanidine Hydrochloride 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 procedures.
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 44 NF 39
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
- Methanol AR Grade
- monobasic sodium phosphate
- phosphoric acid
- sodium dodecyl sulfate
- Acetonitrile
- Distilled water
PROCEDURE:
FINAL MIX A simple HPLC method for determination of Tizanidine hydrochloride in pharmaceutical preparations
Description:
A white to off white granular 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 spectrum of the sample preparation corresponds to spectrum of the standard preparation as obtained in the assay.
The retention time 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 By HPLC
(Limit: 90%-110%)
Procedure:
Solution A: Water and phosphoric acid (44:6)
Buffer: 3.5 g/L of sodium l-pentane sulfonate. Adjust with Solution A or 1 N sodium hydroxide to a pH of 3.0.
Mobile phase: Acetonitrile and Buffer(20:80)
Tizanidine related compound A solution: 0.1 mg/mL of USP Tizanidine Related Compound A RS in methanol.
Tizanidine related compound B solution: 0.1 mg/mL of USP Tizanidine Related Compound B RS in methanol.
Tizanidine related compound C solution: 0.1 mg/mL of USP Tizanidine Related Compound C RS in methanol.
System suitability solution: Transfer 23 mg of USP Tizanidine Hydrochloride RS to a 100 mL volumetric flask, and add 20 mL of Mobile phase and 10 mL each of Tizanidine related compound A solution, Tizanidine related compound B solution, and Tizanidine related compound C solution. Sonicate to dissolve the USP Tizanidine Hydrochloride RS, and dilute with Mobile phase to volume.
Standard solution: 0.046 mg/mL of USP Tizanidine Hydrochloride RS in Mobile phase
Sample solution: Transfer a weighed portion of finely powdered Tablets (NLT 20), equivalent to 20 mg of tizanidine, to a 500-mL volumetric flask. Add 250 mL of Buffer solution, sonicate for 15 min with occasional shaking, and shake by mechanical means for 15 min. Add 100 mL of acetonitrile, and mix. Allow to cool, and dilute with Butter solution to volume. Centrifuge a portion of this solution at2000 rpm or higher for 10 min. Pass a portion of this solution through a filter with a 0.45um or finer pore size, and use the filtrate.
Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC UV 230 nm. For Identification B, use diode array detector in the range of 210-400 nm.
Column: 4.6-mm x 25-cm; 5-l-lm packing L1
Column temperature: 500
Flow rate: 1 mL/min
Injection volume: 10 uL
System suitability
Samples: System suitability solution and Standard solution
Suitability requirements
Resolution: NLT 4.0 between tizanidine and tizanidine related compound C; NLT 4.0 between tizanidine and tizanidine related compound B, System suitability solution.
Tailing factor: NMT 2.0, Standard solution
Relative standard deviation: NMT 2.0%, Standard solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of tizanidine (C9H8CIN5S) in the portion of Tablets taken:
Result= (ru/rs) x (Cs/Cu) x (Mr1/Mr2) x 100
ru= peak response from the Sample solution
rs=peak response from the Standard solution
Cs =concentration of USP Tizanidine Hydrochloride RS in the Standard solution (mg/mL)
Cu = nominal concentration of tizanidine in the Sample solution (mg/mL)
Mr1 =molecular weight of tizanidine, 253.71
Mr2 =molecular weight of tizanidine hydrochloride,290.17
Calculations:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim x Factor
Limit: Tizanidine: 90%-110%of the labeled amount
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.
Hardness Standard Limit:
Thickness Standard Limit:
Length/Diameter Standard Limit:
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.
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.
DISSOLUTION TEST:
USP Apparatus: USP Apparatus Basket
Medium: 500mL 0.1 N hydrochloric acid
Speed: 100 rpm
Time: 15 Minute
Medium Temperature: 37º ± 0.5º
Recommended Sampling Time:Tizanidine:15 Minute
Solution A, Buffer, and Mobile phase: Prepare as directed in the Assay.
Standard solution:
(L/500) mg/mL of USP Tizanidine Hydrochloride RS in Medium, where L is the label claim, in mg.
Sample solution:
Sample per Dissolution (711). Dilute with Medium to a concentration that is similar to the Standard solution.
Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: UV 230 nm
Column: 4.6-mm x 25-cm; 5-um packing L1
Column temperature: 500
Flow rate: 1 mL/min
Injection volume: 20 uL
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of tizanidine (C9H8CIN5S) dissolved:
Result= (ru/rs) x Cs x V x (1/L) x (Mr1/Mr2) x 100
ru= peak response of tizanidine from the Sample solution
rs= peak response of tizanidine from the Standard solution
Cs = concentration of USP Tizanidine Hydrochloride RS in the Standard solution(mg/mL)
V = volume of dissolution Medium, 500 mL
L = Label claim, in mg
Mr1 = molecular weight of tizanidine, 253.71
Mr2 = molecular weight of tizanidine hydrochloride,290.17
Tolerances:
NLT 80% (Q) of the labeled amount of tizanidine (C9H8CIN5S) is dissolved.
Alternate Dissolution Test Method
[NOTE-If the product complies with this test, the labeling indicates that the product meets USP
Dissolution Test 2.]
Medium: 0.1 N hydrochloric acid; 500 mL, deaerated
Apparatus 1: 100 rpm
Time: 15 mins
Standard solution: (L/500) mg/mL of USP Tizanidine Hydrochloride RS in Medium, where L is the label claim, in mg
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-lJm pore size.
Instrumental conditions
(See Ultraviolet-Visible Spectroscopy (857).)
Mode: UV
Analytical wavelength: 228 nm
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of tizanidine (C9H8CIN5S) dissolved:
Result=(Au/As) x Cs x V x (l/L) x (Mr1/Mr2) x 100
Au = absorbance of the Sample solution
As = absorbance of the Standard solution
Cs = concentration of USP Tizanidine Hydrochloride RS in the Standard solution(mg/mL)
V = volume of dissolution Medium, 500 mL
L = label claim, in mg
Mr1 = molecular weight of tizanidine, 253.71
Mr2 = molecular weight of tizanidine hydrochloride,290.17
Tolerance:
The amount of drug dissolve in solution for each tablet is not less Than 80% (Q) of the amount stated on the label for Tizanidine (C9H8CIN5S) at 30 minutes.
CONTENT UNIFORMITY TEST:
Proceed as directed in the assay.
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