| GENERAL MATERIAL INFORMATION | |
| General Information | Dapagliflozin Propanediol Monohydrate film coated tablets is consisting of Dapagliflozin Propanediol Monohydrate and Excipients. |
| Categories | Antihypertensive |
| Composition | Each film coated tablet contains:
Dapagliflozin Propanediol Monohydrate equivalent to Dapagliflozin |
| Reference | In-House Specification |
| Sample Quantity | Chemical Analysis = 60 Tablets
Microbiology Analysis = 20 Tablets |
| 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°.
|
| S.NO. | TESTS | SPECIFICATIONS | REFERENCE | ||
| 1. | Description | IH | |||
| 2. | Average weight | ± 3.0% | IH | ||
| 3. | Uniformity of weight | ± 7.5 % of average weight | IH | ||
| 4. | Identification
|
In the assay, the principal peak in the chromatogram obtained with the test solution should correspond to the principal peak in the chromatogram obtained with the reference solution | |||
| 5. | Hardness | NLT 4.0 Kg/Cm2 | |||
| 6. | Disintegration Time | NMT 30 min | |||
| 7. | Water Content | NMT 10.0% W/W | |||
| 8. | Dissolution | NLT 70% (D) of the label claim dissolve in 45 minutes | |||
| 9. | Leak Test | Should be Pass | |||
| 10. | Uniformity of content | 85.0% to 115.0% of the label claim | |||
| 11. | Assay: | ||||
| Each Film-coated tablet contains: | Limit | ||||
| Claim | In mg | In % | |||
| Dapagliflozin Propanediol Monohydrate equivalent to Dapagliflozin | 10 mg | 9.0 mg to 11.00 mg | 90% to 110% | ||
| S.NO. | TESTS | SPECIFICATIONS | REFERENCE | ||
| 1. | Description | IH | |||
| 2. | Average weight | ± 3.0% | IH | ||
| 3. | Uniformity of weight | ± 7.5 % of average weight | IH | ||
| 4. | Identification
|
In the assay, the principal peak in the chromatogram obtained with the test solution should correspond to the principal peak in the chromatogram obtained with the reference solution | |||
| 5. | Hardness | NLT 4.0 Kg/Cm2 | |||
| 6. | Disintegration Time | NMT 30 min | |||
| 7. | Water Content | NMT 10.0% W/W | |||
| 8. | Dissolution | NLT 70% (D) of the label claim dissolve in 45 minutes | |||
| 9. | Leak Test | Should be Pass | |||
| 10. | Uniformity of content | 85.0% to 115.0% of the label claim | |||
| 11. | Assay: | ||||
| Each uncoated tablet contains: | Limit | ||||
| Claim | In mg | In % | |||
| Dapagliflozin Propanediol Monohydrate equivalent to Dapagliflozin | 5 mg | 4.5 mg to 5.5 mg | 90% to 110% | ||
STANDARD TESTING PROCEDURE
- Description:
Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula.
Average weight (mg) = wt of 20 tablets (gm) x 1000
20
- 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.
Tablets were weighed individually and the percentage of deviation of its weight from the average weight was determined for each tablet. Formula to calculate the percentage of deviation.
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:
By HPLC: In the assay, the principal peak in the chromatogram obtained with the test solution should correspond to the principal peak in the chromatogram obtained with reference solution.
5.0) Hardness:
Take individually 10 tablets; check the hardness of each tablet by using automatic hardness test apparatus. Note the minimum hardness and maximum hardness. It shall be within specification.
6.0) 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 15mm below the surface of the liquid, and at its lower point is at least 25mm 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) Dimension of Tablet:
8.0) Water Content:
Primary Standardization of reagent: Place about 25-30 ml of dehydrated methanol in the titration vessel and add sufficient KF reagent to give the characteristic end point. Add quickly 1.2 drop of water. Accurately weighed by the difference and titration to the endpoint. The water equivalent factor F in mg of weight, in mg of water and v is the volume in ml of the reagent required.
Procedure: Transfer 25-30 ml of dehydrated methanol to the titration vessel, and titrate with KF reagent standardized earlier, to the electrometric end point to consume any moisture that may be present. Quickly and accurately add 250 mg of sample, mix, and again titrate with the reagent to the electrometric end point. Calculate the per cent of water content using the formula.
Water Content = (V-F) x100/Spl. Wt.
Where, V: Volume of KF reagent Consumed (ML)
F: Water equivalence factor of reagent in mg/ml.
8.0) 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.
9.0) Dissolution:
Dissolution Medium: pH 4.5 acetate buffer (Weigh accurately about 29.9 gm of sodium acetate trihydate in 1000ml of water, adjust pH 4.5 with glacial acetic acid).
Apparatus: Paddle
Medium: 1000 ml
Time: 45 minutes
Speed: 60 rpm
Temperature: 37°C ± 0.5°C
Solvent Mixture: Prepare a homogeneous mixture of acetonitrile: Methanol in the ratio of (800:200) mix well and sonicate degas.
Buffer Preparation for mobile phase: Take 2000ml of water and adjust pH 1.90 with ortho phosphoric acid and socinate for 10 minutes and filter with 0.45µ PVDF membrane filter
Mobile Phase: Prepare a homogenous mixture of buffer and solvent mixture in the ratio (660:340) mix well and sonicate to degas.
Diluents: Use dissolution medium as a diluents.
Blank preparation: Use dissolution medium as a diluents.
NLT 70 %(D) of the label claim dissolve in 45 min.
10.0) 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 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.
11.0) Assay:
Solvent mixture: prepare a homogeneous mixture of Acetonitrile: Menthol in the ratio of (800:200) mix well and Sonicate degas
Buffer preparation for mobile phase: Take 2000 ml of water and adjust pH 1.90 (±0.05) with ortho phosphoric acid.
Mobile phase: prepare a homogeneous mixture of buffer and solvent mixture in the ratio (660:340) mix well and sonicate to degas.
Diluent 1: A mixture of 90 volume of acetonitrile and 10 volume of water and degas .
Diluent 2: A mixture of 80 volume s of water and 20 volumes of Acetonitrile mix and degas.
Blank : Use diluent 2 as a blank.
Reference Solution: Weigh accurately 30 mg of Depagliflozin Propanediol Monohydrate Ws in 50 ml volumetric flask, add 25 ml of diluent 1 and Sonicate to desolve and diluent up to the mark with Diluent 1 amd mix well. Transfer 5 ml solution into 50 ml volumetric flask And dilute up to the mark nwith diluent 2 and mix.
Test solution: For 5 mg label claim: take 10 intact tablets weigh and transfer into 100 ml volumetric flask
Add 10 ml ofr water and sonocate for 5 minutes. Add 60 ml of acetonitrile and Sonicate for 30 minutes with intermittent shaking. Dilute up to the mark with Acetoneitrile and mix.Centrifuge the sample. Then pipette out the 5 ml of this solution into 50 ml volumetric flask and dilute up to the mark with diluent 2 and mix well Filter the solution through 0.45µ PVDF filter.
Chromatography system
Mode : LC
Detector : UV 225 nm
Column : Kinetic C18 (75 nm X 4.6) 2.6 µm or equilent column is suitable.
Flow rate : 1.2 ml/min
Injection volume : 20µl
Column Temp. : 5°C
Run Time : 10 minutes
Rinsing solution : water acetonitrile (20:80)
Sampler cooler temp. : 5 ml
Procedure: Set up the chromatographic system. Inject blank preparation (in single) and standard preparation (in five replicates). Record the chromatogram to evaluate the system suitbility parameter as mentioned below.
System suitability parameter:
- The USP theoretical plate count for Dapaglifizin Propenediol Monohydrate peak in standard preparation (1st injection) should not be less than 2500.
- The USP tailing factor for Dapaglifizin propanediol Monohydrate peak in standard preparation (1st injection ) should not less than 0.
- % RSD for area of Dapaglifizin propenediol Monohydrate peak in five replicate injection of standard preparation should not more then 2.0.
If system suitability passes then inject sample preparation (in single) and record the chromatograms.
Calculation:
Factor: 408.873/503.0
Sample Area X Standard Dilution X Potancy X Factor X Avg. wt.
————————————————————————————————
Standard Area X Sample Dilution
Calculate the contant of Dapaglifizin in the table.
13.0) MICROBIOLOGICAL PURITY:
Perform the test according to requirements of IP,
Total aerobic Microbial count (TAMC): NMT 103 CFU/g
Total combined yeasts/Moulds count (TYMC): NMT 102 CFU/g
Pathogens: in 1gm drug.
Escherichia Coli – Should be absent
Pseudomonas aeroginosa – Should be absent
Salmonella – Should be absent
Staphylococcus aureus– Should be absent
Abbreviations:
Wt.: Weight
ml: Millilitre
inHg: Inch of Mercury
O.P.A: Orthophosphoric acid
G.A.A: Glacial acetic acid
mg: Milligram
STD: Standard
rpm: Rotations per minute
NaOH: Sodium Hydroxide
HCl: Hydrochloric acid
