STP FOR ARIPIPRAZOLE TABLETS

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.

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%

4.0)  Identification Test:

In the assay, the principal peak in the chromatogram obtained with the test solution (b) corresponds to the peak in the chromatogram obtained with the reference solution (a).

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)    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.

If obviously cracked, chipped or broken tablets are present in the sample after tumbling, the sample fails the test.

9.0)  Dissolution:

Medium: 1000ml of 0.1 M Hydrochloric acid

Time: 30 minutes

Speed: 100 rpm

Withdraw a suitable volume of the medium.

Determine by liquid chromatography.

Test solution: Centrifuge the medium at 3500 rpm for 15 minutes and use the supernatant solution. Dilute if necessary, with the dissolution medium.

Reference solution: Dissolve a quantity of aripiprazole reference standard in acetonitrile and dilute with the dissolution medium to obtain a solution of the             same concentration as that of the test solution.

Chromatographic system:

• A stainless steel column 15cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm),(such as YMC ODS)
• Mobile phase: a mixture of 50 volumes of buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, add 2ml of triethylamine, adjusting the pH to 3.0 with O.P.A., 25 volumes of acetonitrile and 25 volumes of methanol.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 250nm,
• Injection volume: 20µl

Inject the reference solution and test solution.

Calculate the content of Aripiprazole in the medium.

Limit: NLT 70% of the stated amount of Aripiprazole.

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)    Related substance:

Determined by liquid chromatography.

Test solution: Weigh and powder 10 tablets. Disperse a quantity of powder containing 25mg of aripiprazole in 70ml of the mobile phase with the aid of ultrasound for 45 minutes and dilute to 100ml with the mobile phase. Centrifuge this solution at 3500 rpm for 15 minutes. Dilute 5.0ml of the supernatant liquid to 25.0ml with the mobile phase.

Reference solution: A 0.003 per cent w/v solution of Aripiprazole reference standard in the mobile phase.

Chromatographic system:

• A stainless steel column 25cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm),(such as YMC ODS)
• Mobile phase: a mixture of 50 volumes of buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, add 2ml of triethylamine, adjusting the pH to 3.0 with O.P.A., 25 volumes of acetonitrile and 25 volumes of methanol.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 220nm,
• Injection volume: 20µl

Inject the reference solution. The test is not valid unless the column efficiency is not less than 3000 theoretical plates and the tailing factor is not more than 2.0.

Inject the test solution. The area of any secondary peak is not more than 1.0 per cent and the sum of areas of all the secondary peak is not more than 2.0 per cent, calculated by area normalization method.

12.0)    Uniformity of content:

(For tablets containing 10mg or less than 10mg or less than 10 per cent w/w of active ingredient)

Determine by liquid chromatography

Test solution: Disperse one tablet in 10ml of acetonitrile with the aid of ultrasound for 20 minutes. Add 80ml of the mobile phase in this solution further sonicate for 50 minutes and dilute to 100.0ml with the mobile phase. Centrifuge this solution at 3500 rpm for 15 minutes. Dilute 5ml of the supernatant liquid to 50ml with the mobile phase.

Reference solution: Dissolve a quantity of aripiprazole reference standard in acetonitrile and dilute with the mobile phase to obtain a solution of the same concentration as that of the test solution.

Chromatographic system:

• A stainless steel column 15cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm),(such as YMC ODS)
• Mobile phase: a mixture of 50 volumes of buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, add 2ml of triethylamine, adjusting the pH to 3.0 with O.P.A., 25 volumes of acetonitrile and 25 volumes of methanol.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 250nm,
• Injection volume: 20µl

Calculate the content of Aripiprazole in the tablet.

13.0)    Assay:

Determined by liquid chromatography.

Test solution: Weigh and powder 20 tablets. Disperse a quantity of powder containing 30mg of aripiprazole in 10ml of acetonitrile with the aid of ultrasound for 20 minutes. Add 75ml of the mobile phase in the solution, further sonicate for 40 minutes and dilute to 100ml with the mobile phase. Centrifuge this solution at 3500 rpm for 15 minutes. Dilute 5.0ml of the supernatant liquid to 50.0ml with the mobile phase.

Reference solution: Dissolve 30mg of aripiprazole in 10ml of acetonitrile with the aid of ultrasound and dilute to 100.0ml with the mobile phase. Dilute 5ml of this solution to 50ml with mobile phase.

Chromatographic system:

• A stainless steel column 15cmX4.6mm packed with octadecylsilane bonded to porous silica (5µm),(such as YMC ODS)
• Mobile phase: a mixture of 50 volumes of buffer solution prepared by dissolving 6.8g of potassium dihydrogen orthophosphate in 1000ml of water, add 2ml of triethylamine, adjusting the pH to 3.0 with O.P.A., 25 volumes of acetonitrile and 25 volumes of methanol.
• Flow rate: 1ml per minute,
• Spectrophotometer set at 250nm,
• Injection volume: 20µl

Inject 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.

Calculate the content of Aripiprazole in tablets.

Formula:

Area of Test      STD Wt.(mg)  5            50               100       Potency

—————–X————–X——-X—————X——–X———–X Average wt.

Area of STD        100              50      Test Wt.(mg)     5           100

Acceptance criteria: 90.0%-110.0%

14.0)    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

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