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GENERAL MATERIAL INFORMATION |
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| General Information | Domperidone uncoated tablets is consisting of Domperidone and Excipients. |
| Categories | Antiemetic |
| Composition | Each film coated tablet contains:
Domeperidone IP …………10 mg |
| Reference | Indian Pharmacopoeia 2022 |
| Sample Quantity | Chemical Analysis = 100Tablets
Microbiology Analysis = 20 Tablets |
| Shelf Life | 24 Months
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| Hazards and Precaution, If any | Use nose mask and hand gloves while sampling at bulk stage
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| Storage | Store protected from moisture at a temperature not exceeding 30°.
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SPECIFICATION OF FINISH PRODUCTS-10mg
| S.NO. | TESTS | SPECIFICATIONS | REFERENCE | |||
| 1. | Description | White color round shaped, uncoated tablet having one side mid break line and other side plain
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IH |
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| 2. | Average weight | 190mg ± 3%
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IH | |||
| 3. | Uniformity of weight | Within ±7.5% of the Average weight
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IP | |||
| 4. | Identification | A Determine by thin –layer chromatography.
B In the assay , the principal peak in the in the chromatogram obtain with test solution corresponds to the peak in the chromatogram obtained from reference solution.
|
IP |
|||
| 5. | Hardness | NLT 3 kg/cm2
|
IH | |||
| 6. | Disintegration Time | NMT 30 Minutes
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IP | |||
| 7. | Dissolution | Q. NLT 70%
|
IP | |||
| 8 | Leak Test | Should be Pass
|
IP | |||
| 9. | Related substance | Determine by liquid chromatography
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IP | |||
| 10. | Uniformity of content | 85.0% to 115.0% | IP | |||
| 11. | Assay: | |||||
| Each uncoated tablet contains: | Limit | |||||
| Claim | In mg | In % | IP
|
|||
| Domeperidone I.P. | 10 mg | 9.0 mg to 11.0mg | 95% to 105% | |||
| 12. | Microbial Limit Test : # |
IP |
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| a)Total Bacterial count | NMT 1000 cfu/gm | |||
| b)Total Fungal Count | NMT 100cfu/gm | |||
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c)Specific pathogens
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Escherichia Coli | Should be absent | ||
| Salmonella abony | Should be absent | |||
| Staphylococcus aureus | Should be absent | |||
| Pseudomonas aeruginosa | Should be absent | |||
| Clostridium sporogenes | Should be absent | |||
| Shigella boydii | Should be absent | |||
| Candida albicans | Should be absent | |||
SPECIFICATION OF STABILITY ANALYSIS-10mg
| S.NO. | TESTS | SPECIFICATIONS | REFERENCE | |||
| 1. | Description | White color round shaped, uncoated tablet having one side mid break line and other side plain |
IH |
|||
| 2. | Average weight | 190 mg ± 3% | IH | |||
| 3. | Identification | A Determine by thin –layer chromatography.
B In the assay , the principal peak in the in the chromatogram obtain with test solution corresponds to the peak in the chromatogram obtained from reference solution. |
IP |
|||
| 4. | Hardness | NLT 3 kg/cm2 | IH | |||
| 5. | Disintegration Time | NMT 30 Minutes | IP | |||
| 6 | Dissolution | Q. NLT 70% | IP | |||
| 7. | Related substance | Determine by liquid chromatography | IP | |||
| 8. | Uniformity of content | 85.0% to 115.0% | IP | |||
| 9. | Assay: |
IP |
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| Each film coated tablet contains: | Limit | |||||
| Claim | In mg | In % | ||||
| Domeperidone I.P. | 10 mg | 9.0 mg to 11.0mg | 95% to 105% | |||
| 10 | Microbial Test # |
IP |
||||
| a)Total Bacterial count | NMT 1000 cfu/gm | |||||
| b)Total Fungal Count | NMT 100cfu/gm | |||||
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c)Specific pathogens
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Escherichia Coli | Should be absent | ||||
| Salmonella abony | Should be absent | |||||
| Staphylococcus aureus | Should be absent | |||||
| Pseudomonas aeruginosa | 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: Visual
- Average Weight: Check weight of 20 tablets at random and calculate the average weight by formula.
Average weight (mg) = wt of 20 tablets (gm) x 1000
20
3.0) 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 than 250mg | ±7.5% |
- Identification Test: Determine by thin layer chromatography, coating the plate with silica gel F254 or using a precoated plate (such as Merck silica gel 60 F254 Plates)
Mobile phase: A mixture of 5 volumes of a solution prepared by dissolving 1.36g of sodium acetate in 50 ml of water, adjusting the pH to 407 with dilute acetic acid and adding sufficient water to produce 100 ml, 18 volumes of methanol, 23 volumes of dichloromethane and 54 volumes of ethyl acetate.
Test solution: Shake a quantity of the powdered tablets containing 10 mg of domperidone with 10 ml of a mixture of equal volumes of dichloromethane and methanol and filter through glass microfiber filter (such as whatman GF/C).
Reference solution: A 0.127 per cent w/v solution of domperidone maleate reference standard in a mixture of equal volumes of dichloromethane and methanol.
Apply to the plate 10 µl of each solution. After development, allow the plate to dry in air and examine under ultraviolet light at 254 nm. Spray the plate with potassium iodobismuthate solution and examine again. With each method of visualization, the principal spot in the chromatogram obtained with the test solution corresponds to that in the chromatogram obtained with the reference solution.
- In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
5.0) Hardness:
The standard method used for tablet hardness testing is compression testing. The tablet is placed between two jaws that crush the tablet. The machine measures the force applied to the tablet and detects when it fractures.
- Disintegration Time:
Unless otherwise stated in the individual monograph, introduce one tablet into each tube and add a disc to each tube. The assembly is suspended in the liquid medium in a suitable vessel, preferably a 1-litre beaker. The volume of liquid is such that the wire mesh at its highest point is at least 15 mm below the surface of the liquid, and at its lower point is at least 25 mm above the bottom of the beaker. At no time should the top of the basket-rack assembly become submerged. There is a thermostatic arrangement for heating the liquid and maintaining the temperature at 37±2°.
If 1 or 2 tablets fail to disintegrate, repeat the test on 12 additional tablets; not less than 16 of the total of 18 tablets tested disintegrate.
If the tablets adhere to the disc and the preparation under examination fails to comply, repeat the test omitting the disc. The preparation complies with the test if all the tablets in the repeat test disintegrate.
7.0) Friability:
The test is applicable to compressed tablets and is intended to determine the physical strength of tablets. Tablets with a unit weight equal to or less than 650 mg, take a sample of whole tablets corresponding as near as possible to 6.5 g. For tablets with a unit weight of more than 650mg, 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.
The test is run only once unless the results are difficult to interpret or if the weight loss is greater than the target value, in which case, the test is repeated twice and the mean of the three tests is determined.
% Friability = W1 – W2 X 100
W1
W1= Initial weight W2= Final weight
A maximum loss of weight (From a single test or from the mean of three tests) not greater than 1.0 percent is acceptable for most tablets.
If obviously cracked, chipped or broken tablets are present in the sample after tumbling, the sample fails the test.
8.0) Dissolution:
Apparatus No 2: Paddle
Medium: 900 ml of 0.1 M HCl. (51 ml of concentrated HCl. in 6000 ml water)
Speed: 50 rpm
Time: 45 minutes
Withdraw a suitable volume of the medium and filter. Measure the absorbance of the filtrate, diluted with the dissolution medium if necessary, at 286 nm using the dissolution medium as the blank. Calculate the content of Domperidone in the medium from the absorbance obtained from a solution of known concentration domperidone maleate.
Limit: Q. NLT 70% of the stated amount of Domperidone.
9.0) 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 up to 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.
10.0) Related substances: Determine by liquid chromatography.
NOTE-Prepare the following solutions immediately before use.
Test solution. To a quantity of the powdered tablets containing 50 mg of domperidone add 10 ml of a mixture of equal volumes of 0.01 M hydrochloric acid and methanol, mix with the aid of ultrasound for 20 minutes and filter through a glass microfibre filter (such as Whatman GF/C).
Reference solution (a). Dilute 1.0 ml of the test solution to 200.0 ml with a mixture of equal volumes of 0.01 M hydrochloric acid and methanol. Dilute 1.0 ml of the resulting solution to 2.0 ml with a mixture of equal volumes of 0.01 M hydrochloric acid and methanol.
Reference solution (b). A solution containing 0.01 per cent w/v of domperidone maleate IPRS and 0.015 per cent w/v of droperidol IPRS in a mixture of equal volumes of 0.01 M hydrochloric acid and methanol.
Chromatographic system
-a stainless steel column 10 cm x 4.6 mm, packed with base-deactivated, end-capped octadecylsilyl silica gel (3 μm) (Such as Hypersil BDS),
– mobile phase: A. methanol, B. a 0.5 per cent ammonium acetate, w/v solution of
– a gradient programme using the conditions given below. flow rate: 1.5 ml per minute,
-spectrophotometer set at 280 nm. injection volume: 10 µl.
| Time
(in min.) |
Mobile phase A
(per cent v/v) |
Mobile phase A
(per cent v/v) |
| 0 | 30 | 70 |
| 10 | 100 | 0 |
| 12 | 100 | 0 |
| 14 | 30 | 70 |
Equilibrate the column for at least 30 minutes with methanol and equilibrate with the initial mobile phase for at least 5 minutes.
Inject a mixture of equal volumes of 0.01 Mhydrochloric acid and methanol as a blank, the test solution and reference solution (a) and (b). The test is not valid unless, in the chromatogram obtained with reference solution (b), the resolution between the two principal peaks is at least 2. If necessary adjust the concentration of methanol in the mobile phase or adjust the time programme for the linear gradient.
In the chromatogram obtained with the test solution the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.25 per cent) and the sum of the areas of any secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with the reference solution (a) (0.5 per cent). Ignore any peak in the chromatogram obtained with the blank solution and any peak with an area less than 0.2 times the area of the peak in the chromatogram obtained with reference solution (a) (0.05 per cent).
11.0) Assay. Determine by liquid chromatography
Solvent mixture. Equal volumes of 0.01 M hydrochloric acid and methanol.
Test solution. Disperse 10 intact tablets in the solvent mixture to produce a solution containing 0.02 per cent w/v of domperidone, mix with the aid of ultrasound for 30 minutes and filter through a glass microfiber filter (such as Whatman GF/C). Dilute 50.0 ml of the solution to 100.0 ml with the solvent mixture.
Reference solution. A 0.0127 per cent w/v solution of domperidone maleate IPRS in the solvent mixture.
Use the chromatographic system as described under Related substances.
Inject the reference solution. The test is not valid unless the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 2.0 per cent Inject the reference solution and the test solution.
Calculate the content of Domperidone in the tablets.
Formula:
Absorbance of test 1 100 25 potency
———————–X————X———–X————-X———-X———-X Avg. wt.
Absorbance of std 100 25 test wt. 1 100
12.0) MICROBIOLOGICAL PURITY
Perform the test according to STP/ML002
Abbreviations:
Wt.: Weight
mg: Miligram
ml: Milileter
STD: Standard
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
O.P.A.: orthophosphoric acid
HCl: hydrochloric acid
13.0) Revision History:-
| S. No. | Reason For Change | Revision No. |
