In this blog post, we are going to share the Esomeprazole Magnesium Enteric Coated Pellets Testing Procedure step by step for your ease. Esomeprazole is a very common drug for stomach treatment. We have also shared and you can read here the Esomeprazole Magnesium Pellets 22.5 % Raw Material Testing
Now we to our main topic Esomeprazole Magnesium Enteric Coated Pellets Testing Procedure Standard Analytical Procedure
REFERENCE: USP 44, NF 39
APPROVAL BLOCK
| Title | Designation | Signature/Date |
| Written By: | Quality Control Analyst | |
| Reviewed By: | Quality Control Manager | |
| Verified By: | Quality Assurance In-charge | |
| Approved By: | Technical Operation Director |
Distribution List
| Sr. # | Department | New revision # | Retrieval Revision # | Signature & Date |
| 1 | ||||
| 2 |
DOCUMENT REVISION CONTROL
| Rev. # | Date | Initiated By | Page # | Nature of Amendment | Done By |
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1.0 PURPOSE:
To describe the procedure for testing of raw material Esomeprazole Magnesium EC Pellets.
2.0 SCOPE:
This document describes the basic principles, defines the responsibilities and lays down the procedure for the analytical testing of Esomeprazole Magnesium EC Pellets.
3.0 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.
4.0 REFERENCE:
USP 44, NF 39
5.0 MATERIAL AND EQIUPMENT:
- Analytical balance
- FTIR
- HPLC
- Hot Plate
- Vacuum Assembly
- pH Meter
- Muffle Furnace
- Spatula
- Sulphuric Acid
- Distilled Water
- Glassware
- Polarimeter
- Sodium Hydroxide
- Hydrochloric acid
- Methanol
- Triethylamine
- Phosphoric Acid
- Acetonitrile
- 2-Propanol
- Alcohol
6.0 PROCEDURE:
6.1 SAMPLING PLAN:
Take sample from each container and identify individually. Make representative sample and divide into two portions. 1st portion for remaining analysis and 2nd portion for keeping sample.
6.2 RETAIN SAMPLE:
Pack sufficient quantity of sample in polythene bag and seal in aluminium foil finally. Keep the sample at recommended storage conditions for at least 1 year after expiry/retest date.
6.3 RECORD KEEPING:
Analysis records including raw data generated during the application of this procedure will be kept at least one year after the expiry or one year after the last distribution whichever is longer.
6.4 DESCRIPTION:
6.4.1 SPECIFICATIONS:
White to off white spherical enteric-coated pellets
6.4.2 PROCEDURE:
Spread approximately 2.0 g of the sample over the cleaned and dried petri dish and examine visually against a white background. Check the appearance of color, nature and any visible foreign particles.
6.5 IDENTIFICATION
6.5.1 SPECIFICATIONS:
Identification by HPLC & by UV
6.5.2 PROCEDURE:
6.5.2.1 By HPLC
The retention time of the major peak in the chromatogram of the test solution should corresponds to that in the chromatogram of the standard solution, as obtained by HPLC method.
6.5.2.2 By UV Spectrophotometer:
UV spectrum of the sample should be concordant with that of the standard
6.6 WATER: (By Karl Fischer)
6.6.1 SPECIFICATION:
Water Determination, = not more than 5.0 %
6.6.2 PROCEDURE
Add about 20 mL of methanol to the titration vessel and neutralized it with K.F. reagent. Quickly add about 0.100 g of accurately weighed of the crushed sample, stir to dissolve and titrate to the electrometric end point with K.F. reagent. Record the water contents.
6.7 PELLETS SIZE
6.7.1 SPECIFICATIONS: Limit: NLT 90% pass through mesh 14 and NLT 90% Retain on mesh 16
6.7.2 PROCEDURE:
6.7.2.1 Arrange the sample: Collector, X1 # sieve, X2 # sieve. Weigh and transfer around 100 grams of the sample into X1 # sieve and shake for 5 minutes. Collect the pellets pass through mesh X1sieve (W X1) and pellets retain on mesh # X2 sieve (W X2). Calculate the % retains and passing as follows;
6.7.2.2 Calculation:
% pass through X1 # mesh = W X1 in Gram x 100 / weight of sample in Gram
% retain on X2# mesh = W X2 in Gram x 100 / weight of sample in Gram
6.8 DISSOLUTION TEST
6.8.1 Acid Release
- Apparatus USP: Apparatus II
- Medium: 0.1 N HCL ,300 ml
- Sample Interval: 120 minutes
- RPM: 100
- Temperature: 37 oC + 0.5 oC
6.8.1.1 By UV- Spectrophotometer
6.8.1.2 Sample preparation:
Weigh and transfer the pellets equivalent to 20mg of Esomeprazole (1.035mg of Esomeprazole Mg is equivalent to 1.0mg of Esomeprazole) individually in each of 6 dissolution flasks, containing 300ml of 0.1N HCl, equilibrated at 37+ 0.5oC. Immediately start the apparatus and run for 2 hrs. After 2 hours lift the paddle and take 10 ml of the sample. Dilute it to 50ml with 0.1N NaOH. Sonicate it for 15 minutes.
6.8.1.3 Reference preparation:
Accurately weigh Omeprazole working standard equivalent to 50mg, and transfer to a 100ml volumetric flask and sonicate it to dissolve in 0.1N NaOH. Slightly heat if required. Cool it to room temperature.
Make volume up to mark with same solvent. Dilute 1 ml of stock solution to 50 ml with the same solvent.
Procedure
Take reading of both sample and ref solutions in a 1 cm cell on a U.V/ Visible spectrophotometer at 305 nm
Calculation:
%age = Abs. of sample prep. x conc. of stand prep. x 100
Abs. of standard Prep conc. of assay prep.
Limits: NMT 10% should release after 2 hrs.
6.8.2 Dissolution in Buffer
- Apparatus USP: Apparatus II
- Medium: Buffer pH = 6.8,1000 ml
- Sample Interval: 30 minutes
- RPM: 100
- Temperature: 37 oC + 0.5oC
- Weight taken Equivalent to 20 mg
6.8.3 By HPLC
6.8.3.1 Preparation of Buffer:
700ml of 0.086M dibasic sodium Phosphate added to 300ml acid stage medium and pH adjusted to 6.8 with 2N HCl or 2N NaOH.
6.8.3.2 Standard Preparation:
Prepare a solution containing 2mg/ml of omeprazole working standard. Dilute 1ml of this solution to 100ml with pH 6.8 phosphate buffer. Immediately add 2.0ml of 0.25M NaOH to 10ml of this solution and mix.
(note: Do not allow the solution to stand before adding the sodium hydroxide)
6.8.3.3 Sample Preparation:
After completion of acid stage, add 700 ml of 0.086M Dibasic Sodium phosphate solution to the acid medium, in each basket. Adjust the pH to 6.8 with 2N HCl or 2N NaOH, if required. Run the apparatus for 30 minute in buffer solution.
After completion of specified period, transfer 10ml of filtrate to a beaker containing 2 ml of 0.25M NaOH. Mix well and protect from light.
6.8.4 Chromatographic Condition:
Proceed as directed in assay preparation
6.8.5 Procedure
Inject equal volume of both sample and standard solution in the chromatograph and record the area due to major peaks.
- %age = Area of the major peak of assay prep. x conc. of std prep x 100
- Area of major peak of ref. std prep. conc. of assay prep
- Limit NLT 75% should release in buffer stage in 30 minutes
6.9 RELATED SUBSTANCES (BY HPLC ) Chromatographic conditions
- Column 150 x 4.6 mm 5u, C18
- Flow Rate: 1.0ml/min
- Wavelength: 280 nm
- Temperature 37 oC+ 0.5oC
- Load 20 uL
- Run Time About 20 min
Preparation of Buffer: Prepare a pH 7.6 phosphate buffer by mixing 5.2ml of 1.0M monobasic Sodium Phosphate buffer and 63ml of 0.5M dibasic sodium phosphate buffer and diluting with water to 1000ml.
Solution A
Mix 100ml of acetonitrile and 100ml of the buffer. Dilute with water to 1000.
Solution B Mix 800ml of acetonitrile and 10ml of buffer. Dilute with water to 1000ml.
Diluent : Dissolve 5.24g of tribasic sodium phosphate dodecahydrate in water. Add 110ml of 0.5M dibasic sodium phosphate and dilute with water to 1000ml.
Standard Preparation:
Prepare 1mg/ml each of Omeprazole and Omeprazole related compound A WS, in methanol.
Dilute it to µg/ml solution of each , in a mixture of diluents and water (1:4).
Sample Preparation:
Transfer about 80-90mg of pellets, to a 200ml volumetric flask, add 20ml of methanol, and shake for 30s. Add 40ml of diluent, shake with hand and then sonicate for a few minutes. Cool and dilute with water to volume. Filter and use.
Suitability requirement:
Resolution: NLT 2.5 between Omeprazole Sulphone and Omeprazole
Procedure: Inject equal volume of both sample and standard solution in the chromatograph and record the area due to major peaks.
Results:
Calculate the %age of any individual impurity in the portion of Esomeprazole taken:
- (ru/ rt) x 100
- ru = Peak response for each impurity
- rt = sum of all peak responses
- Limit: Omeprazole Sulfone = NMT 0.5%
- Total Impurities = NMT 2.0%
| Time | Solution A | Solution B |
| 0 Minute | 10 | 0 |
| 10 Minute | 80 | 20 |
| 30 Minute | 0 | 100 |
| 31 Minute | 100 | 0 |
| 45 Minute | 100 | 0 |
6.10 ASSAY BY HPLC
6.10.1 Chromatographic conditions
- Column: 150 x 4.6 mm 5u, C18
- Flow Rate: 1.0ml/min
- Wavelength: 302 nm
- Temperature: 37 oC+ 0.5oC
- Load: 20 uL
6.10.2 Preparation of Buffer:
Prepare a pH 7.3 Phosphate buffer by mixing 10.5ml of 1M Monobasic sodium Phosphate buffer and 60ml of 0.5M dibasic Sodium Phosphate Buffer and dilute with water to 1000 ml.
6.10.3 Preparation of Mobile phase:
Mix 350ml of Acetonitrile and 500ml of Buffer. Dilute with water to 1000ml.
6.10.4 Diluent:
Dissolve 5.24g of tribasic sodium phosphate dodecahydrate in water. Add 110ml of 0.5M dibasic sodium phosphate and dilute with water to 1000ml. adjust the pH to 11.0, if required.
6.10.5 Standard Preparation:
Transfer about 20mg of Omeprazole WS to a 500ml volumetric flask and dissolve in about 20ml of Ethanol. Add 80ml of diluent and dilute with water to volume. This solution contains 0.04mg/ml of Omeprazole.
6.10.6 Sample Preparation:
Weigh and mix the pellets of not fewer than 10 gm. Transfer an accurately weighed portion of the pellets, equivalent to about 20 mg of Esomeprazole, (1.035mg of Esomeprazole Mg is equivalent to 1.0mg of Esomeprazole) to a 100ml volumetric flask, add about 60 ml of Diluent and stir for about 20 minutes then sonicate it for further 10 minutes for complete dissolution. Add 20ml of Ethanol. Sonicate for about 10-20 minutes to dissolve the pellets. Dilute with Diluent to volume, mix and pass through a membrane filter having 0.45-µm porosity.
Dilute 10ml of filtrate to 50ml with water to obtain 0.04mg/ml concentration of sample’s solution.
Note: Assay preparation should be prepared in duplicate.
PROCEDURE:
Separately inject equal volumes (about 10 μL)of the standard preparation and the assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
6.10.7 SYSTEM SUITABILITY:
6.10.7.1 RELATIVE STANDARD DEVIATION:
NMT 2.0 % for standard solution.
6.10.8 CALCULATIONS:
Average Area Under Curve of Assay preparation x Standard dilution x Potency of standard
Average Area Under Curve of Standard preparation x Sample dilution
Limits: 90% _ 110% of the claimed Amount
6.11 STORAGE:
Store in air tight container, protected from light at controlled room temperature.
7.0 RISK ANALYSES:
EVIDENCE OF RECORDS & REFERENCES
USP44, NF39 Certificate of Analysis Raw Material
FORMAL KPIs (Key Performance Indicators)
Storage Condition Contamination of sampling tools
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