QualityGuidances

• Description: Visual
• 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       
• 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 for calculate

the percentage of deviation = (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%

•    Identification Test:

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.

•      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.

•       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.

•      Dimension of Tablet:

Length, breadth and thickness are determined by vernier in mm

•    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 6.5g. 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.

          Formula: initial wt. – after friability wt. x100 / initial wt.

            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.

•     Dissolution:

            Apparatus: Paddle

Medium: 500ml of buffer solution prepared by dissolving 0.8 gm of monobasic potassium phosphate and 0.2 gm of dibasic potassium                                      phosphate in 1000ml of water; adjust the pH to 6.0 with O.P.A.

Speed: 100rpm

Time: 30 minutes

            Limit: NLT 85% of the labeled amount of Alprazolam is dissolved.

            Withdraw a suitable volume of the medium and filter, discarding about 10ml of the filtrate.

Determine by liquid chromatography

            Test solution: The filtrate obtained as given above

            Reference solution: A 0.005 percent w/v solution of alprazolam reference standard in methanol. Dilute the solution with the                              dissolution medium to obtain a solution of about the same concentration as the test solution.

            Chromatographic system:                                                              

• A stainless steel column 10cm X4.6mm, packed with octysilane bonded to porous silica (5µ),
• Mobile Phase: a mixture of 60 volumes of buffer solution, 35 volumes of acetonitrile, and 5 volumes of tetrahydrofuran,
• Flow rate: 1ml per minute,
• Spectrophotometer set at 254nm,
• Injection volume: 20µl

Inject reference solution. The test is not valid unless the column efficiency is not less than 500 theoretical plates, and the relative standard deviation for replicate injections is not more than 3.0 per cent.

Inject reference solutions and test solution.

Calculate the content of Alprazolam.

•    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.

•    Uniformity of content: Determined by liquid chromatography.

            Test solution: Transfer one tablet to a container, add 0.4ml of water on to the tablet, allow the tablet to stand for 2 minutes and swirl the container to disperse the tablet. Add sufficient acetonitrile to produce a solution containing 0.0025 per cent w/v of alprazolam. Shake to mix and centrifuge, if necessary.

            Reference solution: A 0.0025 per cent w/v solution of alprazolam reference standard in acetonitrile.

Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with porous silica particles (5to 10µm),
• Mobile Phase: a mixture of 850 volumes of acetonitrile, 80 volumes of chloroform, 50 volumes of 1-butanol, 20 volumes of water and 0.5 volumes of glacial acetic acid.
• Flow rate: 2.0ml per minute,
• Spectrophotometer set at 254nm,
• Injection volume: 10µl or 20µl

Inject the reference solution and test solution.

Calculate the content of Alprazolam in the tablet.

•     Assay: Determined by liquid chromatography.

Test solution: Place 5 tablets in a flask, add 2ml of water and swirl to disperse the tablets. Add sufficient acetonitrile to produce 25.0ml. Shake for 10 to 15 minutes and centrifuge if necessary. Dilute a portion of the clear solution with acetonitrile to produce a solution containing 0.0025 per cent w/v of alprazolam.

Reference solution: A 0.0025 per cent w/v solution of alprazolam reference standard in acetonitrile.

            Chromatographic system:

• A stainless steel column 25cm X4.6mm, packed with porous silica particles (5to 10µm),
• Mobile Phase: a mixture of 850 volumes of acetonitrile, 80 volumes of chloroform, 50 volumes of 1-butanol, 20 volumes of water and 0.5 volumes of glacial acetic acid.
• Flow rate: 2.0ml per minute,
• Spectrophotometer set at 254nm,
• Injection volume: 10µl or 20µl

Inject reference solution. The test is not valid unless the relative standard deviation for replicate injections for each peak is not more than               2.0 percent.  Inject reference solution and the test solution.

Calculate the content of Alprazolam in the tablet.

        Acceptance criteria: 90.0%-110.0%

        Formula:

Area of Test      STD Wt. (mg)             5            100            Potency

—————–X—————–X——–X—————X———–X   Average weight

Area of STD          100                         50     Test Wt. (mg)     100

•     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

mg: Miligram

ml: Milileter

STD: Standard

inHg: Inch of Mercury

rpm: Rounds per minute

CFU: Colony forming unit

O.P.A.: Orthophosphoric acid

w/v: Weight/volume