ANALYSIS METHOD OF ESOMEPRAZOLE GASTRO-RESISTANT CAPSULES(40 mg)

nirvesh400
 

GENERAL MATERIAL INFORMATION
General Information Esomeprazole  Gastro-resistant  hard gelatin capsules contains Esomeprazole Magnesium Trihydrate  pallets & dummy pallets.
Categories Antiulcer
Composition Each Hard gelatin capsule contains:

Esomeprazole Magnesium

Trihydrate  IP……………………….40 mg
Reference Indian Pharmacopoeia 2022/
Sample Quantity Chemical Analysis = 100 Capsule

 

Microbiology Analysis = 20 Capsule
Shelf Life 24 Months
Hazards and Precaution, If any Use nose mask and hand gloves while sampling at bulk stage
Storage Store protected from moisture at a temperature not exceeding 30°.

 

SPECIFICATION OF FINISH PRODUCT

 

S.NO. TESTS SPECIFICATIONS REFERENCE
1. Description Pink colour cap & transparent colour body  hard gelatin capsule filled with white pellets IH
2. Average weight 415mg/cap± 3 % IH
3. Average Fill 340mg/cap± 3 % IH
4. Uniformity of weight Within ± 7.5% of the Average weight IP
5. Identification The peak corresponding to esomaprazole and enantiomer  R is not less then 1.0.The ratio of retention time of esomeprazole peak in the reference solution and the test solution  Should be between 0.98 and 1.02 IP
6. Disintegration Time NMT 30 min IP
7. Dissolution

 

 Q. NLT 70% of the stated amount of Esomeprazole IP
8. Leak Test Should be Pass IP
9. Related Substace In the chromatogram obtained with the test solution the area of peak corresponding to omeprazole impurity A is not more than 0.5%, the area of any other secondary peak is not more than o.5% and the sum of areas of all the secondary peaks is not more than 2.0%

 

calculate by area normallization

 IP
10. Enantiomeric Purity The peak corresponding to esomaprazole and enantiomer  R is not less then 1.0.The ratio of retention time of esomeprazole peak in the reference solution and the test solution  Should be between 0.98 and 1.02. IP
11 Assay: IP
Each hard gelatin contains: Limit
Claim In mg Claim
Esomeprazole Magnesium Trihydrate IP 40mg 36.0mg to 44.0mg 90% to 110%
12. Microbial Limit Test IP
a)Total Bacterial count NMT 100 cfu/gm
b)Total Fungal Count NMT 10cfu/gm
 

c)Specific pathogens

 

 Escherichia Coli Should be absent
Salmonella abony Should be absent
Staphylococcus aureus Should be absent
Pseudomonas eruginosa Should be absent
Clostridium sporogenes Should be absent
Shigella boydii Should be absent
Candida albicans Should be absent

 

SPECIFICATION OF STABILITY ANALYSIS

 

S.NO. TESTS SPECIFICATIONS REFERENCE
1. Description Pink colour cap & transparent colour body  hard gelatin capsule filled with white pellets. IH
2. Average weight 415mg/cap± 3 % IH
3. Average Fill 340mg/cap± 3 % IH
4. Identification The peak corresponding to esomaprazole and enantiomer  R is not less then 1.0.The ratio of retention time of esomeprazole peak in the reference solution and the test solution  Should be between 0.98 and 1.02

 

  

 

IP
5. Disintegration Time NMT 30 min IP
6. Dissolution

 

 Q. NLT 70% of the stated amount of Esomeprazole IP
7. Related Substace In the chromatogram obtained with the test solution the area of peak corresponding to omeprazole impurity A is not more than 0.5%, the area of any other secondary peak is not more than o.5% and the sum of areas of all the secondary peaks is not more than 2.0%

 

calculate by area normallization

  

 

 

 

IP
8. Enantiomeric Purity The peak corresponding to esomaprazole and enantiomer  R is not less then 1.0.The ratio of retention time of esomeprazole peak in the reference solution and the test solution  Should be between 0.98 and 1.02.

 

 IP
9. Assay:  

 

 

IP
Each hard gelatin contains: Limit
Claim In mg Claim
Esomeprazole Magnesium Trihydrate IP 40mg 36.0mg to 44.0mg 90% to 110%
10. Microbial Limit Test  

 

 

 

IP
a)Total Bacterial count NMT 100 cfu/gm
b)Total Fungal Count NMT 10cfu/gm
 

c)Specific pathogens

 

 Escherichia Coli Should be absent
Salmonella abony Should be absent
Staphylococcus aureus Should be absent
Pseudomonas eruginosa Should be absent
Clostridium sporogenes Should be absent
Shigella boydii Should be absent
Candida albicans Should be absent

 

* Related Substance: Once in a year         # Microbial Limit Test: Once in a Year

 

STANDARD TESTING PROCEDURE

 

  • Description:
  • Average Weight: Check weight of 20 Capsules randomly and calculate the average weight by formula.

Average weight (mg) =   wt of 20 tablets (gm) x 1000

20

  • Average Fill: Check weight of 20 Capsules at random. And calculate the average weight by above formula and subtract empty weight of capsule from average weight
  • Uniformity of weight:

Weigh 20 tablets selected at random and calculate the average weight. Not more than two of the individual weights deviate from the average weight by more than the percentage shown in table.

Weigh the tablets individually and calculate the percentage of deviation for each tablet by using formula:

Deviation (%) = Weight of each tablet – average weight    x 100

Average weight

 

Average weight of tablets Percentage deviation
More than 80mg but Less then 250mg ±7.5%
250mg or More ±5%
  • Identification Test:

Enantimeric(See Test)

  • Disintegration Time:

Comply with the disintegration test. Unless otherwise directed in the individual monograph use water as the medium. If the capsules float on the surface of the medium, a disc may be added. If the capsules adhere to the disc, attach a removable piece of stainless steel woven gauze with mesh aperture of 2.0±0.2 mm to the upper plate of the basket rack assembly and carry out the test omitting the discs. Operate the apparatus for 30 minutes unless otherwise directed.

  • Dissolution:Apparatus No. 2( Paddle)

Medium 900 ml of 0.1 Mhydrochloric acid Speed and time. 100 rpm and 2 hours.

Tap the granules from a capsule slightly with a glass rod to make them settle to the bottom. Rotate the paddle at 100 rpm for 2 hours, drain the solution slowly without losing any granules. Transfer them quantitatively to a 100-ml volumetric flask, add 20 ml of 0.1 M sodium hydroxide and mix with the aid of ultrasound. Dilute to volume with 0.1 M sodium hydroxide, centrifuge about 15 ml for 5 minutes and dilute 5.0 ml of the clear supernatant liquid to 50.0 ml with the mobile phase. Using the resulting solution as the test solution, carryout the determination as described under Assay Calculate the content of CH,,N,O,S in the supernatant liquid. Calculate the percentage of esomeprazole released in the acid medium by subtracting the content of C, H,,N,O,S in the test solution from the total content of esomeprazole determined in the Assay.

Complies with the acceptance criteria given under acid stage.

  1. Apparatus No. 2 (Paddle),

Medium. 900 ml of phosphate buffer pH 6.8.

Speed and time. 100 rpm and 45 minutes.

Tap the granules from a capsule slightly with a glass rod to make them settle to the bottom. Rotate the paddle at 100 rpm for 45 minutes and filter the solution. Immediately transfer 5.0 ml of the solution to a test tube containing 1.0 ml of 0.1 M sodium hydroxide. Prepare the standard solution having a known concentration similar to the expected concentration and in similar manner to the test solution. Calculate the content of CH, N,O,S in the medium.

  1. Not less than 70 per cent of the stated amount of
  • Leak test:

The apparatus is used to test for the integrity of packed strips, blisters and Alu-Alu Blister pack containing tablets. Ensure apparatus bath is filled with purified water upto mark indicated and add 0.5% crystal violet solution in water. Samples are placed into the desiccators and the lid is placed in position. The pump starts to produce a vacuum 15inHg inside the desiccators and the vacuum is held for 1 minute. The sample remains at the required vacuum level for given time interval buzzer will sound after time is over and will cut off the vacuum pump. As the package is immersed in a colored dye solution the venting of the desiccators will allow any holes to be penetrated by the dye and the contents of the flexible packaging will also be stained with the same coloring material. Examine all the strips for any leakage by opening the pockets manually. If anyone pocket shows evidence of leakage, reject the sample, stop the Blister / Strip machine and immediately take corrective action.

  • Related substance:

NOTE-Use freshly prepared solution and protected from

light Solvent mixture. Dissolve 5.24 g of trisodium orthophosphate in water, add 110.0 ml of 0.5 M disodium hydrogen orthophosphate and make up the volume to 1000.0 ml with water, adjusted to pH 11.0 with 0.1 M sodium hydroxide solution

Buffer solution. Mix 5.2 ml of 1.0 M disodium hydrogen orthophosphate buffer and 63.0 ml of 0.5 M sodium dihydrogen orthophosphate buffer diluted to 1000.0 ml with water, adjusted to pH 7.6 with 0.1 M sodium hydroxide solution.

Test solution. Disperse a quantity of mixed contents of capsules containing 80 mg of esomeprazole in 20.0 ml methanol, add 40.0 ml solvent mixture and mix with the aid of ultrasound for 5 minutes and dilute to 200.0 ml with the water.

Reference solution: Dissolve 10 mg each of omeprazole IRS and omeprazole sulphone IPRS (omeprazole impurity A) in 100.0 ml methanol. Dilute 1.0 ml of the solution to 100.0 ml in a mixture of 1 volume of solvent mixture and 4 volume of water

Chromatographic system

-a stainless steel column 10 cm x 4.6 mm, packed with octadecylsilane bonded to porus silica (3 m).

-mobile phase: A mixture of 100 ml of acetonitrile and 100 ml of buffer solution and diluted to 1000 ml with water,

  1. B. a mixture of 800 ml of acetonitrile and 10 ml of buffer solution and diluted to 1000 ml with water .

-a gradient programme using the conditions given below.

flow rate: 1 ml per minute, spectrophotometer set at 302 nm.

injection volume: 20 μl.

 

 

Time

(in min )

 Mobile Phase A

(Per cent v/v)

 Mobile Phase B

(Per cent v/v)
0 100 0
10 80 20
30 0 100
31 100 00
45 100 00

The relative retention time with reference to omeprazole for omeprazole sulphone is 0.93. Inject the reference solution. The test is not valid unless resolution between the peaks due to omeprazole and omeprazole impurity A is not less than 2.5

Inject the test solution. In the chromatogram obtained with the test solution the area of peak corresponding to omeprazole impurity A is not more than 0.5 per cent, the area of any other secondary peak is not more than 0.5 per cent and the sum of areas of all the secondary peaks is not more than 2.0 per cent, calculated by area normalization.

 

  • Enantiomeric purity:

Determined by liquid chromatography

Solvent mixture: Dissolve 5.24 g of trisodium phosphate in water, add 110 ml of 0.5 M disodium hydrogen phosphate and make up the volume to 1000 ml with water and adjusted to pH 11.0.

Test solution: Shake a quantity of the mixed contents of 20 capsules containing 20 mg of esomeprazole in 120 ml solvent mixture, add 40 ml ethanol and mix with the aid of ultrasound for 5 minutes and dilute to 200 ml with the solvent mixture. Dilute 1.0 ml of the solution to 10.0 ml in water.

Reference solution. Dissolve 20 mg of omeprazole IPRS in 120 ml solvent mixture, add 40 ml ethanol and mix with the aid of ultrasound for 5 minutes and dilute to 200 ml with the solvent mixture. Dilute 1.0 ml of the solution to 10.0 ml in water

Chromatographic system

-a stainless steel column 10 cm x 4.0 mm, packed with immobilized alpha 1 acid glycoprotein on special silica particles (5 µm).

Mobile Phase: a mixture of 150 ml of acetonitrile and 85 ml of buffer solution prepared by dissolving 26.6 g of disodium hydrogen orthophosphate and 55.2 g sodium dihydrogen orthophosphate in 1000 ml water, adjusted to pH 6.0 and finally diluted to 1000 ml with water.

flow rate: 1 ml per minute,

spectrophotometer set at 302 nm,

injection volume: 20 μl.

The elution order of enantiomers is R-enantiomer and then S- enantiomer which is esomeprazole peak

Inject the reference solution and the test solution. The test is not valid unless the resolution between the peaks corresponding to esomeprazole and enantiomer R is not less than 1.0. The ratio of the retention time of esomeprazole peak in the reference solution and the test solution should be between 0.98 and 1.02.

  • Assay. Determined by liquid chromatography (2.4.14).

Solvent mixture. Dissolve 5.24 g of trisodium phosphate in water, add 110 ml of 0.5 M di-sodium hydrogen phosphate and make up the volume to 1000 ml with water and adjusted to pH 11.0 with 0.1 M sodium hydroxide solution.

Test solution. Weigh and mix the contents of 20 capsules. Disperse a quantity of the mixed content containing about 20 mg of esomeprazole with 60 ml of the solvent mixture, shake for 20 minutes to dissolve the pellets. Add 20 ml of methanol and mix with the aid of ultrasound and dilute to 100.0 ml with the solvent mixture. Dilute 2.0 ml of the solution to 10.0 ml using water, filter. Store the solution protected from light.

Reference solution. Dissolve 10 mg omeprazole IPRS in 10 ml methanol, add 40 ml solvent mixture and further dilute with water to obtain a concentration of 0.004 per cent of omeprazole.

Chromatographic system

-a stainless steel column 15 cm x 4.6 mm, packed with octadecylsilane bonded to porus silica (5 µm).

– mobile phase: a mixture of 350 ml of acetonitrile, 500 ml of buffer solution prepared by mixing 10.5 ml 1.0 M sodium dihydrogen orthophosphate and 60.0 ml 0.5 M disodium hydrogen orthophosphate in 1000 ml of water, adjusted to pH 7.3 and finally diluted to 1000 ml with water,

flow rate: 1 ml per minute, spectrophotometer set at 302 nm,

injection volume: 20 ul.

Inject the reference solution. The test is not valid unless the relative standard deviation for replicate injection is not more than 2.0 per cent.

Inject the reference solution and the test solution

Calculate the content of Esomeprazole  in the capsules

  • MICROBIOLOGICAL PURITY:

Perform the test according to STP/ML/002

Abbreviations:

Wt.      : Weight

mg       : Milligram

G.A.A             : Glacial acetic acid

ml        : Millilitre

CFU    : Colony forming unit

STD     : Standard

Rpm    : Rotations per minute

inHg   : Inch of Mercury

 

  • Revision History:-
S. No. Reason For Change Revision No.

 

Specification