Esomeprazole Magnesium Pellets 22.5 % Raw Material Testing

Esomeprazole Magnesium Pellets 22.5 % Raw Material Testing RS has been added to the USP Reference Standards section and the table numbers in the test for Organic Impurities have been updated.
The Esomeprazole Magnesium Delayed-Release pellets Revision Bulletin supersedes the currently official monograph

Esomeprazole Magnesium Pellets 22.5 %
Molecular formula: ……………C34H36MgN6O6S2 3H2O
Molecular weight: ……………… 767.17

APPROVAL BLOCK

Distribution List

DOCUMENT REVISION CONTROL

1-DESCRIPTION:-

A white to of-white color Enteric coated Pellets

2-IDENTIFICATION

A. By UV Method:

Take sufficient quantity of Enteric Coated Pellets equivalent and grind into fine powder. Take sufficient quantity about 0.178gm (equivalent to 20 mg of Esomeprazole) of Esomeprazole Pellets in 100.0ml of volumetric flask. Add 50.0ml of 0.1N NaOH, sonicate the solution until completely dissolved, filter if necessary and makeup the volume up to 100.0ml with 0.1M NaOH. Further dilute 5.0ml of this solution to 100.0ml 0.1N NaOH.
Measure the absorption spectrum of resulting solution in the range of 230nm to 400nm .
Resulting solution will show maximum absorbance at about s 305nm.
Showing +ve Identification of Esomeprazole.

B. By HPLC Method:

In the HPLC chromatogram ,retention time of assay preparation for Esomeprazole Mg Enteric coated pellets correspond to the retention time of standard preparation.

3- Dissolution

• A-Dissolution in 0.1M HCl:
• Medium : 300 ml 0.1M HCl
• Apparatus : 2: 100
• Temperature : 37 ±0.5°C
• Time : 2 hours

Sample Preparation:

Set the instrument’s parameters as mentioned above after getting the temperature, place a quantity of pellets equivalent to 20 mg Esomeprazole in each of 6 dissolution vessels containing 300 ml of 0.1M HCl as a medium. Place the Enteric Coated Pellets equivalent To 20 mg to make settle at the bottom with the help of dry pipette, taking care to exclude the air bubble from the pellets surface and start the apparatus at 100 RPM for 2 hours.
Filter the resulting solution through 0.45µm filter paper (Acidic Medium Solution A) .Take 100ml volumetric flask ,add 10ml 1M NaOH , 30ml Acidic Medium Solution A and make volume up to mark with water.

Standard Preparation:

Dissolved 20.0mg of Esomeprazole powder working standard and dissolved in 100.0ml 0.1M NaOH. Dilute 10.0ml of this solution to 100.0ml with 0.1M NaOH.
Measure the absorption of resulting sample and standard solution at 305nm.
%age Assay (Dissolution) =

Absorbance Of sample solution X %Age Potency Of Standard
Absorbance Of Standard solution

Tolerances: NMT 10% (Q) of the labeled amount of Esomeprazole dissolved.

Dissolution in Phosphate Buffer 6.8:

Buffer stage medium: pH 6.8 phosphate buffer. Proceed as directed in Acid resistance stage with a new set of Enteric Coated Pellets. After 2 h with Acid stage medium, continue with a pH 6.8 phosphate buffer as follows. To the vessel, add 700 mL of 0.086 M dibasic sodium phosphate, and adjust with 2 N hydrochloric acid or 2 N sodium hydroxide, if necessary, to a pH of 6.8 + 0.05.

• Medium : 900 ml Phosphate Buffer pH 6.8
• RPM : 100
• Temperature : 37 ±0.5°C
• Time : 30 minutes in Phosphate Buffer pH 6.8

Preparation of phostphate Buffer pH 6.8:

Sample Preparation:

Set the instrument’s parameters as mentioned above after getting the temperature, place enteric coated pellets in each of 6 dissolution vessel, containing 900 ml of phosphate buffer pH 6.8 as a medium. Place the Enteric Coated Pellets equivalent To 20 mg to make settle at the bottom with the help of dry pipette, taking care to exclude the air bubble from the pellets surface and start the apparatus at 100 RPM for 30 minutes. At the end of 30 minutes withdraw solution from zone midway between surface of medium and top of rotating peddle enteric coated pellets equivalent to 20 mg 1 cm from the vessel wall. Filter the resulting solution. Dilute 90.0ml of this solution to 100.0ml with 10ml 1M NaOH.

Standard Preparation:

Dissolved 20.0mg of Esomeprazole powder working standard and dissolved in 100.0ml 0.1M NaOH. Dilute 5.0ml of this solution to 100.0ml with 0.1M NaoH.
Measure the absorption spectrum of resulting sample solution and standard solution in the range of 240—400nm. Resulting solution will show maximum absorbance at about 305 nm.
Calculate the percentage Dissolution of Esomeprazole by applying formulae.

%age Dissolution =

Absorbance Of sample solution X %Age Potency Of Standard
Absorbance Of Standard solution

BY HPLC METHOD:

Standard solution: Prepare a solution containing 2 mg/ml of USP Omeprazole RS in alcohol. Dilute this solution with pH 6.8 phosphate buffer to obtain a solution containing (LI1000) mg/mL, where L is the label claim, in mg/ Enteric Coated Pellets equivalent To 20 mg . Immediately add 2.0 ml of 0.25 M sodium hydroxide to 10.0 ml of this solution, and mix.{NOTE-Do not allow the solution to stand before adding the sodium hydroxide solution .]

Sample solution: After 30 min in pH 6.8 phosphate buffer, pass a portion of the solution under test through a suitable filter. Transfer 5.0 mL of the filtrate to a suitable glassware containing 1.0 mL of 0.25 M sodium hydroxide. Mix well. Protect from light.
Buffer, Mobile phase, System suitability, and Chromatographic
system: Proceed as directed in the

Assay.
Analysis

Samples: Standard solution and Sample solution
Calculate the percentage of esomeprazole (C1TH19N,O,S) dissolved:
Result”, (rulrs) x (Cs/L) x V x 100
ru ‘” peak response from the Sample solution
fs ‘” peak response from the Standard solution
Cs = concentration of the Standard solution
(mg/mLJ
L ‘” label claim (mg/ Enteric Coated Pellets equivalent To 20 mg )
V ‘” volume of Medium, 1000 ml
Tolerances: Enteric Coated Pellets equivalent To 20 mg 75% (Q) of the labeled amount of esomeprazole
(C17H19N]O]S) is dissolved.
Tolerance : NLT 75 % of the labeled amount of Esomeprazole as Mg Enteric coated pellets
6- Assay (Contents of Esomeprazole As Mg Enteric coated pellets):

UV-VISIBLE SPECTROPHOTOMETRIC METHOD

Sample Preparation:

Take previously weighed and grind ,sufficient quantity of Pellets.
Take sufficient quantity about 0.178gm , equivalent to 20 mg of of Esomeprazole in 100.0ml of volumetric flask. Add 50.0ml of 0.1N NaOH, sonicate the solution until completely dissolved, filter if necessary and makeup the volume upto 100.0ml with 0.1M NaOH. Further dilute 5.0ml of this solution to 100.0ml 0.1N NaOH.
Measure the absorption spectrum of resulting solution in the range of 230nm to 400nm .
Resulting solution will show maximum absorbance at about s 305nm.

Standard Preparation:

Dissolved 20.0mg of Esomeprazole powder working standard and dissolved in 100.0ml 0.1M NaOH. Dilute 10.0ml of this solution to 100.0ml with 0.1M NaoH..
Measure the absorption spectrum of resulting solution in the range of 230nm to 400nm .
Resulting solution will show maximum absorbance at about 305nm.
%age Assay =

Absorbance Of sample solution X %Age Potency Of Standard
Absorbance Of Standard solution

Limit : 20.25% to 24.75% AS ESOMEPRAZOLE

7- ALTERNATIVE HPLC ASSAY METHOD:

ASSAY:

Buffer: Prepare a pH 7.3 phosphate buffer by mixing 22.5 ml of 1.0 M monobasic sodium phosphate buffer and 60 ml of 0.5 M dibasic sodium phosphate buffer, and diluting with water to 1000 ml.
Diluent: Prepare a pH 11.0 diluent as follows. Dissolve 5.24 g of tribasic sodium phosphate dodecahydrate in water. Add 110 ml of 0.5 M dibasic sodium phosphate solution, and dilute with water to 1000 ml.

Mobile phase: Mix 350 ml of acetonitrile and 500 ml of the Buffer. Dilute with water to 1000 ml.
Standard solution: Transfer 10 mg of USP Omeprazole RS to a 250ml volumetric flask, and dissolve in about 10 ml of alcohol. Add 40 ml of Diluent, and dilute with water to volume. This solution contains 0.04 mg/ ml of USP Omeprazole RS.

Sample stock solution: Mix the contents of Enteric Coated Pellets equivalent To 20 mg s. Transfer a portion of the Enteric Coated Pellets equivalent To of esomeprazole, to a 100ml volumetric flask, add 60 ml of Diluent, and shake for 20 min to dissolve the pellets. Sonicate for a few min, if needed, to completely dissolve. Add 20 ml of alcohol, and sonicate for a few min. Cool, and dilute with Diluent to volume. Pass a portion of the solution through a filter of 1-um pore size.

Sample solution: 0.04 mg/ml of esomeprazole from the Sample stock solution in water. Store this solution protected from light.

• Chromatographic system
• Detector: UV 302 nm
• Column: 4.6-mm x 15-cm; 5-µm packing L1
• Flow rate: 1 ml/min
• Injection size: 20 µL minimum
• System suitability
• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 2.0%

Calculations:

Calculate the percentage of the labeled amount of esomeprazole (C17H19N3O3S) in the portion of the Enteric Coated Pellets equivalent To 20 mg s taken:

• Result = (rU/rS) x (CS/CU) x 100
• rU = peak response from the Sample solution rS = peak response from the Standard solution
• CS = concentration of USP Omeprazole RS in the
• Standard solution (mg/ml)
• CU = nominal concentration of esomeprazole in the
• Sample solution (mg/ml)

Acceptance criteria: NLT 20.25% and NMT 24.75%

STORAGE:

Preserve in tight containers, protected from light. Store at room temperature.

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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