1.0) Description: Visual
2.0) Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula :
wt of 20 tablets (gm) x 1000 / 20. found avg. wt in mg
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 = (experimental weight – theoretical weight) x 100%
Theoretical weight
| Average weight of tablets | Percentage deviation |
| More than 80mg but Less than 250mg | 7.5% |
| 250mg or More | 5% |
4.0) Identification Test:
Mix a quantity of the powdered tablets containing 50mg of Mirtazapine with 12.5ml of water, add 12.5ml of n-hexane, allow to separate, retain and filter the hexane layer and evaporate the filtrate to dryness. On the residue, determine by infrared absorption spectrophotometry. Compare the spectrum with that obtained with mirtazapine reference standard or with the reference spectrum of Mirtazapine.
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. Although compressive force is applied to the tablet, along the diameter of the tablet at right angles to the applied force.
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:
Length, breadth and thickness are determined by vernier in mm
8.0) Dissolution:
Apparatus: Paddle
Medium: 900ml of 0.1 M HCl,
Speed: 50 rpm
Time: 45 minutes
Limit: NLT 80% of the stated amount of Mirtazapine. Withdraw a suitable volume of the medium and filter.
Determine by liquid chromatography,
Test solution: Dilute the filtrate, if necessary, with the dissolution medium.
Reference solution: Dissolve a quantity of mirtazapine reference standard in the dissolution medium to obtain a solution of known concentration similar to the expected concentration of the test solution.
Chromatographic system:
- A stainless steel column 25cm X4mm, packed with base deactivated octadecylsilane bonded to porous silica (5µm).
- Column temperature: 40°
- Mobile phase: a mixture of 80 volumes of a solution containing 2 volumes of triethylamine and 1000 volumes of a 0.68 per cent w/v solution of potassium dihydrogen orthophosphate, adjusted to pH 3.0 with dilute O.P.A. and 20 volumes of acetonitrile,
- Flow rate: 1.5ml per minute.
- Spectrophotometer set at 292nm,
- Injection volume: about 50µl
Inject reference solution and the test solution.
Calculate the content of Mirtazapine in the dissolution medium.
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,
Solvent mixture: 50 volumes of acetonitrile and 50 volumes of water.
Test solution: Disperse a quantity of the powdered tablets containing 30mg of Mirtazapine with 10ml of the solvent mixture with the aid of ultrasound, dilute to 20ml with the solvent mixture and filter.
Reference solution (a): Dilute 1ml of the test solution to 100ml with the solvent mixture.
Reference solution (b): Dilute 1ml of reference solution (a) to 10ml with the solvent mixture.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with endcapped octadecylsilane bonded to porous silica (5µm).
- Mobile phase: a mixture of 75 volumes of tetrahydrofuran, 125 volumes of methanol, 150 volumes of acetonitrile and 650 volumes of a solution of 1.8 per cent w/v of tetramethylammonium hydroxide, previously adjusted to pH 7.4 with O.P.A.
- Flow rate: 1.5ml per minute.
- Spectrophotometer set at 240nm,
- Injection volume: about 10µl
| Name | Relative retention time | Correction factor |
| Mirtazapine impurity A1 | 0.2 | 1.3 |
| Mirtazapine impurity B2 | 0.3 | 1.3 |
| Mirtazapine impurity C3 | 0.35 | – |
| Mirtazapine impurity D4 | 0.4 | – |
| Mirtazapine (retention time about 16 minutes) | 1.0 | – |
| Mirtazapine impurity E5 | 1.3 | – |
| Mirtazapine impurity F6 | 1.35 | 0.2 |
Inject reference solution (b). The test is not valid unless the signal-to-noise ratio of the principal peak is not less than 10.
Inject reference solution (a), (b) and the test solution. Run the chromatogram twice the retention time of the principal peak. In the chromatogram obtained with the test solution the area of any secondary peak is not more than 0.3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.3 per cent). The sum of the areas of all the secondary peaks is not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (2.0 per cent). Ignore any peak with an area less than the principal peak in the chromatogram obtained with reference solution (b) (0.1 per cent).
11.0) Assay: Determined by liquid chromatography.
Solvent mixture: 50 volumes of acetonitrile and 50 volumes of water.
Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing about 90mg of Mirtazapine with 50ml of the solvent mixture and dilute to 100ml with the solvent mixture. Dilute 1ml of this solution to 10ml with the solvent mixture.
Reference solution: A 0.009 per cent w/v solution of Mirtazapine reference standard in the solvent mixture.
Chromatographic system:
- A stainless steel column 25cm X4.6mm, packed with endcapped octadecylsilane bonded to porous silica (5µm).
- Mobile phase: a mixture of 75 volumes of tetrahydrofuran, 125 volumes of methanol, 150 volumes of acetonitrile and 650 volumes of a solution of 1.8 per cent w/v of tetramethylammonium hydroxide, previously adjusted to pH 7.4 with O.P.A.
- Flow rate: 1.5ml per minute
- Spectrophotometer set at 240nm,
- Injection volume: about 10µl,
Inject reference solution. The test is not valid unless the tailing factor is not more than 2.0.
Inject the reference solution and test solution.
Calculate the content of Mirtazapine in the tablets.
Alternative Method: By UV Spectrophotometer
Test Solution: Weigh and powder 20 tablets. Weight sample equivalent to 25mg of Mirtazapine 100ml volumetric flask add 20ml 0.1 M HCl into it and sonicate to dissolve the test sample. Make up to mark with 0.1 M HCl. Filter and dilute 2ml of this solution to 25ml in 0.1 M HCl.
Reference Solution: Weigh 25mg of reference standard of Mirtazapine in 100ml of volumetric flask. Add 20ml 0.1 M HCl into it and sonicate to dissolve. Make up to mark with 0.1 M HCl. Dilute 2ml of this solution to 25ml with 0.1 M HCl.
Check Absorbance of test as well as reference standard at about 316nm in UV Spectrophotometer.
Calculate the content of Mirtazapine in the tablets.
Formula:
Abs. of Test STD Wt.(mg) 2 100 25 Potency
—————–X————–X———X—————–X——-X———–X Average wt.
Abs. of STD 100 25 Test Wt.(mg) 2 100
Acceptance criteria: 95.0%-105.0%
12.0) 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:
mg: Miligram
ml: Milileter
inHg: Inch of Mercury
rpm: Rounds per minute
CFU: Colony forming unit
w/v: Weight/volume
HCl: hydrochloric acid
O.P.A.: orthophosphoric acid
STD: standard
Wt.: weight
Abs.: Absorbance
