STP FOR OLANZAPINE TABLETS

1.) 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% 250 mg or More 5%

4.0)      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.

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:  0.01M hydrochloric acid; 900ml

Speed: 50rpm

Time: 45 minutes

Limit: NLT 75 percent of the stated amount of olanzapine in the medium.

Withdraw a suitable volume of the medium and filter. Determine by liquid chromatography

Note: Protect all the solution from light.

Test solution: Use the filtrate, if necessary dilute with dissolution medium.

Reference solution: Weigh 16mg of olanzapine reference standard, dissolve in about 2.5ml of acetonitrile and dilute to 25ml with 0.01M hydrochloric acid. Dilute suitably                to get 0.00016 per cent w/v in dissolution medium.

Chromatography System:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile Phase: A mixture of 70 volumes of buffer solution prepared by dissolving 3gm of ammonium dihydrogen orthophosphate in 900ml water, add 2ml of triethylamine and dilute to 1000ml with water. Adjust the pH to 2.5 with orthophosphoric acid and 30 volumes of methanol
• Flow rate: 1ml per minute,
• Spectropohtometer set at 260nm,
• Injection volume: 10µl

Inject the reference solution. The test is not valid unless the tailing factor is not more than 2.0 and the column efficiency is not less than 2500 theoretical plates.

Inject the reference solution and the test solution.

Calculate the content of Olanzapine.

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 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.

10.0)    Assay: Determined by liquid chromatography.

Reference solution: Weigh 25mg of olanzapine reference standard in 50ml volumetric flask. Add 10ml of mobile phase to dissolve the standard. Dilute upto the mark with mobile phase. Dilute 5ml of this solution to 50ml in mobile phase. Filter the solution and inject.

Test preparation: Weigh and powder 20 tablets. Weigh sample containing 5mg of olanzapine in to 100ml volumetric flask. Add 10ml of mobile phase to dissolve the sample. Dilute this upto the mark. Filter and inject the sample.

Chromatography System:

• A stainless steel column 25cm X4.6mm, packed with octadecylsilane bonded to porous silica (5µm)
• Mobile Phase: A mixture of 70 volumes of buffer solution prepared by dissolving 3gm of ammonium dihydrogen orthophosphate in 900ml water, add 2ml of triethylamine and dilute to 1000ml with water. Adjust the pH to 2.5 with orthophosphoric acid and 30 volumes of methanol
• Flow rate: 1ml per minute,
• Spectropohtometer set at 260nm,
• Injection volume: 10µl

Inject the reference solution. The test is not valid unless the tailing factor is not more than 2.0, the column efficiency is not less than 2500 theoratical plates. The relative standard deviation for replicate injections is not more than 2 per cent.

Inject the reference solution and the test solution.

Calculate the content of Olanzapine.

Formula:

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

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

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

Alternative method: (By UV spectrophotometer)

Reference solution:Weigh 25mg of olanzapine reference standard in 50ml volumetric flask. Add 10ml of  methanol and dissolve the standard. Dilute upto the mark with methanol. Dilute 1ml of this solution to 50ml in 0.1M HCl.

Test preparation: Weigh and powder 20 tablets. Weigh sample containing 10mg of olanzapine in to 100ml volumetric flask. Add 10ml of methanol to dissolve the sample. Dilute this upto the mark. Filter and dilute it further 5ml to 50ml in 0.1M HCl.

Scan the solution by UV Spectrophotometer. It will give absorbance maxima at about 260nm. Note down the reading and calculate the content of olanzapine in tablet.

Formula:

Acceptance criteria: 90.0%-110.0%

Formula:

Area of Test      STD Wt.(mg)  1              100                50          Potency

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

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

Acceptance criteria: 90.0%-110.0%

11.0)

Abbreviations:

Wt.: Weight

mg: Miligram

ml: Milileter

STD: Standard

inHg: Inch of Mercury

RPM: Rounds per minute

E.coli: Escherichia coli