Learn how to write a standard specification and Test Procedure for analysis of Azithromycin Tablet 500 mg.
Table of Contents Analysis of Azithromycin Tablet
STANDARD SPECIFICATIONS FOR GRANULES
This specification is checked at the end of the granulation stage.
| Sl. No. | Tests | Specifications |
| 1 | Appearance | A White to off-white granular powder, free from any visible foreign particles |
| 2 | Identification | Must comply with the test of Azithromycin. |
| 3 | Moisture Content | Not more than 6.0% w/w. |
| 4 | Assay by HPLC | a. Average sample content: 90.0%-110.0% of the stated amount of Azithromycin (after blending). |
| b. Individual sample content: 90.0%-110.0% of the stated amount of Azithromycin (after blending). |
STANDARD SPECIFICATIONS FOR CORE TABLET
This specification is checked at the end of the compression stage (core stage).
| Sl. No. | Tests | Specifications |
| 1 | Appearance | A white to off-white oblong shaped tablet having engraved logo on one side and other side plain. |
| 2 | Identification | Must comply with the test of Azithromycin. |
| 3 | Average weight of tablet | 922.00 mg ± 5.0 %. (it will be change as per your formulation) |
| 4 | Uniformity of weight | Not more than 2 of the 20 tablets deviate from the average weight by more than ± 5% and none by more than ± 10 %. |
| 5 | Hardness | Not less than 3.0 kg/cm2. |
| 6 | Thickness | 6.70 mm ± 0.30 mm. |
| 7 | Friability Test | Not more than 1 % w/w. |
| 8 | Disintegration time | Not more than 15 minutes at 37ºC. |
| 9 | Assay by HPLC | a). Average Azithromycin content / Tablet as percentage : 90.0% – 110.0% |
| b). Average Azithromycin content / Tablet: 450.0 – 550.0 mg of the stated amount of Azithromycin (after compression) |
STANDARD SPECIFICATIONS FOR COATED TABLET
This specification is checked at the end of the coating stage (coated /finished tablet).
| Sl. No. | Tests | Specifications |
| 1 | Appearance | A white white oblong shaped tablet having engraved logo on one side and other side plain. (if coating material is white or it will be change with color of coating materials) |
| 2 | Identification | Must comply with the test of Azithromycin. |
| 3 | Average weight of tablet | 925.00 mg ± 5.0 %. (it will be change as per your formulation) |
| 4 | Uniformity of weight | Not more than 2 of the 20 tablets deviate from the average weight by more than ± 5% and none by more than ± 10 %. |
| 5 | Thickness | 6.75 mm ± 0.30 mm. |
| 6 | Disintegration time | Not more than 30 minutes at 37ºC. |
| 7 | Dissolution | Not less than 80% (Q) in 30 Minutes |
| 8 | Assay by HPLC | a). Average Azithromycin content / Tablet as percentage : 90.0% – 110.0% |
| b). Average Azithromycin content / Tablet: 450.0 – 550.0 mg of the stated amount of Azithromycin (after coating) |
ANALYSIS METHOD OF TABLET GRANULES
1. Appearance:
Perform a visual inspection of the granules. Place the blend sample on butter white glazed tile, observe the color. Compare the sample appearance to specification description. The blend should be free of foreign matter.
Note: Observe the above checks and report if any discrepancies.
2. Identification:
Test Procedure: Perform by HPLC Method
Specification:
The retention time of the Azithromycinpeak in the chromatogram of the assay preparation corresponds to that of the standard preparation as directed in the assay.
Note: Observe the above checks and report if any discrepancies
3. Moisture Content:
Perform the test taking 10 gm. sample at 1050C at moisture analyzer.
Note: Observe the above checks and report if any discrepancies
4. Assay Analysis: It tested By HPLC
Reagents:
Mobile Phase: Acetonitrile ꓽ Methanol: Solution A (900 : 300 : 800)
Preparation of Solution A:
4.40 g of Dibasic Potassium Phosphate and 500 mg 1- Octane sodium salt dissolve in 1000 ml water. Adjust pH 8.2 with phosphoric acid.
Diluents: Methanol : Acetonitrile : Solution B (700 : 600 : 700)
Preparation of Solution B:
1.7 g monobasic Ammonium phosphate dissolve in 1000 ml of water, adjust pH 10.0 with ammonium hydroxide.
Standard Preparation:
Transfer about 21 mg of Azithromycin dihydrate WS, accurately weighed, in a 50 ml volumetric flask. Add 30 ml diluents, shake and sonicate for few minutes to dissolve. Volume with same solvent. Finally filter through 0.2 µm of filter trip.
Sample Preparation:
Transfer 500 mg of Azithromycin equivalent powder (about 920mg) in 250 ml volumetric flask, add 120 ml diluents, shake and Sonicate for few minutes. Allow to cool and volume with same solvent. Filter through whatman # 41 filter paper and take 5 ml to 25 ml volumetric flask and volume with diluents.
Chromatographic system specifications:
Column : C18
Flow rate : 2.0 ml/minute.
Wavelength : 210 nm.
Temperature : 50° C
Injection volume : 20 µl.
Run time : 25 minutes.
Test Procedure:
Separately weight equal volume (20µl) of the standard preparation and the sample preparation into the chromatograph. Record the chromatograms and measure the responses for major picks and calculate the content of Azithromycin.
Calculation:
Calculation formula as (%) =
Peak area of Spl X dilution of Std X Standard potency (%) X Avg. Weight X 100
Peak area of Std X dilution of Spl X 500 X 100
Label claim X % of Result
Calculation Formula Azithromycin Content/Tablet = mg.
Percentage(100)
ANALYSIS METHOD OF CORE TABLET
1. Appearance:
Perform the test by visual inspection of the Azithromycin 500 tablets. Randomly select 10 tablets and put on butter white glazed tile, observe the size, shape, color and marking. Compare the sample appearance to specification description. The tablet should be free of foreign matter or surface defects, including sticking, discoloration or disfiguration. By observe white to off-white oblong shaped tablet having engraved ‘‘LOGO’’ on one side and other side plain.
Note: Observe the above checks and report if any discrepancies
2. Identification:
Apparatus
Perform by HPLC Method (assembles and operates the apparatus by following respective SOP)
Specification:
The retention time of the Azithromycinpeak in the chromatogram of the assay preparation corresponds to that of the standard preparation as directed in the assay.
Note: Observe the above checks and report if any discrepancies
3. Average weight:
Apparatus
Electronic balance (assembles and operates the apparatus by following respective SOP)
Test Procedure
Weight 20 tablets and calculate average weight of tablets.
Or Weigh individually 20 tablets selected at random and calculate the average weight in mg.
Average weight (mg), = Weight of 20 tablets in g / 20 x1000
Note: Observe the above checks and report if any discrepancies.
4. Uniformity of weight:
Not more than 2 of the 20 tablets deviate from the average weight by more than ± 5% and none by more than ± 10 %.
Note: Observe the above checks and report if any discrepancies.
5. Hardness:
Apparatus
Hardness Tester (assembles and operates the apparatus by following respective SOP)
This test is intended to determine the resistance to crushing of tablets, measured by the force needed to disrupt them by crushing. Check the hardness of 10 tablets by a suitable hardness tester calculates and record the average hardness of 10 tablets.
Test Procedure
Perform the test following instrument operation Test Procedure. Place the tablet between the jaws of the tester, taking into account, where applicable, the shape, the break-mark and the inscription; With respect to the force application direction, position the tablet in the same manner for every measurement. Ten tablets should be measured, and before making any conclusions, be sure that all tablet pieces have been removed. This Test Procedure does not apply when fully automated equipment is used.
Expression of results
Express the results as the mean, min. and max. Values of the forces measured, all expressed in kg.
Note: Observe the above checks and report if any discrepancies.
6. Thickness:
Apparatus
Thickness Tester (assembles and operates the apparatus by following respective SOP)
Test Procedure
Check the thickness of 10 tablets by a suitable slide calipers or Thickness tester calculates and record the average thickness of 10 tablets and report the observed value (assemble and operate the apparatus by following respective SOP).
Expression of results
Report the mean, minimum, and maximum values from the results.
Note: Observe the above checks and report if any discrepancies.
7. Friability Test:
Apparatus
Friability Tester (assembles and operates the apparatus by following respective SOP)
Test Procedure
Step-1: The test samples are carefully dedusted prior to testing.
Step-2: Perform the test taking at least 10 tablets weight.
Step-3: Place the tablets in the Friability drum and set the Friability Tester to rotate 100 times.
Step-4: Take out the tablets and remove any loose dust from the tablets.
Step-5: Weight the tablets (W2).
Calculate the friability by the following formula:
Friability (%) = (W1 -W2 )/W1 x 100
Generally the test is run once. After tumbling, if the tablet sample contains clearly cracked, cleaved, or broken tablets, the sample fails the test. If the results are difficult to interpret or if the weight loss is greater than the targeted value, the test is repeated twice and mean of the three tests determined.
Note: Observe the above checks and report if any discrepancies.
8. Disintegration time:
Apparatus
Disintegration Tester (assembles and operates the apparatus by following respective SOP)
Test Procedure
Connect the main switch. An arbitrary figure will appear in the digital display. Now set the test time. Place 6 (six) tablets into 6(six) tubes of Disintegration Testing Apparatus. Suspend the tubes in a 1000 ml beaker having 800 ml of purified water maintaining temperature at 37ºC ± 2º C.800 ml of water is required to maintain that the wire mesh at its highest point is at least 25 mm below the surface of water and the lowest point is at 25 mm above the bottom of the beaker. Operate the apparatus & record the time required for disintegration. The tablet pass the test if all six have disintegrated as per specified time mentioned in specification.
Repeat the test with twelve (12) more tablets if one or two don’t entirely dissolve; at least sixteen (16) of the eighteen (18) pills tested must totally dissolve.
Note: Observe the above checks and report if any discrepancies.
9. Assay Analysis:
Apparatus
By HPLC method (assembles and operates the apparatus by following respective SOP)
Reagents:
Mobile Phase: Acetonitrile :Methanol : Solution A = (900 : 300 : 800)
Preparation of Solution A:
4.40 g of Dibasic Potassium Phosphate and 500 mg 1- Octane sodium salt dissolve in 1000 ml water. Adjust pH 8.2 with phosphoric acid.
Diluents: Methanol : Acetonitrile : Solution B = (700 : 600 : 700)
Preparation of Solution B:
1.7 g monobasic ammonium phosphate dissolve in 1000 ml of water, adjust pH 10.0 with ammonium hydroxide.
Standard Preparation:
Transfer about 20 mg of Azithromycin dihydrate WS, accurately weighed, in a 50 ml volumetric flask.
Add 30 ml diluents, shake and sonicate for few minutes to dissolve. Volume with same solvent. Finally filter through 0.2µm of filter trip.
Sample Preparation:
Transfer 500 mg of Azithromycin equivalent powder (about 920mg) in 250 ml volumetric flask, add 120 ml diluents, shake and Sonicate for few minutes. Allow to cool and volume with same solvent. Filter through what man # 41 filter paper and take 5 ml to 25 ml volumetric flask and volume with diluents.
Chromatographic system specifications:
Column : C18
Flow rate : 2.0 ml/minute.
Wavelength : 210 nm.
Temperature : 50° C
Injection volume : 20 µl.
Run time : 25 minutes.
Test Procedure:
Separately weight equal volume (20µl) of the standard preparation and the sample preparation into the chromatograph. Record the chromatograms and measure the responses for major picks andcalculate the content of Azithromycin.
Calculation:
alculation formula as (%) =
Peak area of Spl X dilution of Std X Standard potency (%) X Avg. Weight X 100
Peak area of Std X dilution of Spl X 500 X 100
Label claim X % of Result
Calculation Formula Azithromycin Content/Tablet = mg.
Percentage(100)
Also Read: Pharmaceutical Microbiology
ANALYSIS METHOD OF COATED TABLET (FINISHED PRODUCT)
1. Appearance:
Perform the test by visual inspection of the Azithromycin 500 tablets. Randomly select 10 tablets and put on butter white glazed tile, observe the size, shape, color and marking. Compare the sample appearance to specification description. The tablet should be free of foreign matter or surface defects, including sticking, discoloration or disfiguration. By observe a white to off white oblong shaped film coated tablet having engraved “LOGO” on one side and other side plain.
2. Identification:
Apparatus
Perform by HPLC Method (assembles and operates the apparatus by following respective SOP)
Specification:
The retention time of the Azithromycinpeak in the chromatogram of the assay preparation corresponds to that of the standard preparation as directed in the assay.
Note: Observe the above checks and report if any discrepancies
3. Average weight:
Apparatus
Electronic balance (assembles and operates the apparatus by following respective SOP)
Test Procedure
Weight 20 tablets and calculate average weight of tablets.
Or Weigh individually 20 tablets selected at random and calculate the average weight in mg.
Average weight (mg), = Weight of 20 tablets in g / 20 x1000
Note: Observe the above checks and report if any discrepancies.
4. Uniformity of weight:
Not more than 2 of the 20 tablets deviate from the average weight by more than ± 5% and none by more than ± 10 %.
Note: Observe the above checks and report if any discrepancies.
5. Thickness:
Apparatus
Thickness Tester (assembles and operates the apparatus by following respective SOP)
Test Procedure
Check the thickness of 10 tablets by a suitable slide calipers or Thickness tester calculates and record the average thickness of 10 tablets and report the observed value (assemble and operate the apparatus by following respective SOP).
Expression of results
Report the mean, minimum, and maximum values from the results.
Note: Observe the above checks and report if any discrepancies.
6. Disintegration time:
Apparatus
Disintegration Tester (assembles and operates the apparatus by following respective SOP)
Test Procedure
Connect the main switch. An arbitrary figure will appear in the digital display. Now set the test time. Place 6 (six) tablets into 6(six) tubes of Disintegration Testing Apparatus. Suspend the tubes in a 1000 ml beaker having 800 ml of purified water maintaining temperature at 37ºC ± 2º C.800 ml of water is required to maintain that the wire mesh at its highest point is at least 25 mm below the surface of water and the lowest point is at 25 mm above the bottom of the beaker. Operate the apparatus & record the time required for disintegration. The tablet pass the test if all six have disintegrated as per specified time mentioned in specification.
Repeat the test with twelve (12) more tablets if one or two don’t entirely dissolve; at least sixteen (16) of the eighteen (18) pills tested must totally dissolve.
Note: Observe the above checks and report if any discrepancies.
7. Dissolution:
Apparatus: HPLC method
Dissolution Testing Apparatus Condition:
Apparatus : USP II (Paddle)
Dissolution medium : Phosphate buffer pH 6.0
Volume : 900 ml
Revolution : 75 rpm
Temperature : 37°C ± 0.5°C
Dissolution Time : 30 minutes.
Reagents:
Preparation of Phosphate buffer pH 6.0:
Dissolve 40.83 g potassium dihydrogen phosphate in 1500 ml water + 168 ml(1.344 g) of 0.2 M sodium
hydroxide in the solution + Adjust the final volume upto 6000 ml with purified water + adjust pH 6.0 with sodium hydroxide or phosphoric acid solution.
Mobile Phase: Acetonitrile : Methanol : Solution A (900 : 300 : 800)
Preparation of Solution A:
4.40 g of Dibasic Potassium Phosphate and 500 mg 1- Octane sodium salt dissolve in 1000 ml water. Adjust pH 8.2 with Phosphoric acid.
Diluents: Acetonitrile: Solution B (200: 800)
Preparation of solution B:
17.5 g Dibasic Potassium Phosphate dissolve in 1000 ml water, adjust pH 8.0 with phosphoric Acid.
Standard Preparation:
Transfer about 27 mg of Azithromycin dihydrate WS, accurately weighed, in a 50 mL volumetric flask, dilute to volume with dissolution medium and mix well. Pipette 5 ml of this solution in a 10 ml volumetric flask, dilute to volume with diluents and mix well.
Sample Preparation:
On completion of test, collect 20 ml of solution from the vessel and filter. Pipette 5 ml of this filtrate in a 10 ml volumetric flask; dilute to volume with diluents & mix well.
Chromatographic system specification:
Column : C18
Flow rate : 2.0 ml/minute.
Wavelength : 210 nm.
Temperature : 50° C
Injection volume : 20 µl.
Run time : 25 minutes.
Testing Procedure:
Separately weight equal volume (20µl) of the standard preparation and the sample preparation into the chromatograph. Record the chromatograms and measure the responses for major picks and calculate the release of Azithromycin.
Calculation:
A C/50 X 5/10 X P X 100
——- X = % of Azithromycin released in 30 minutes.
B D/900 X 5/10 X 100
Where,
A = Area of Sample preparation.
B = Area of Standard preparation.
C = Weight of Standard preparation in mg.
D = Label claim of Tablet.
P = Potency (%) of Standard substance.
Limit: Not less than 80 %( Q) in 30 Minutes.
8. Assay Analysis:
Apparatus
By HPLC method (assembles and operates the apparatus by following respective SOP)
Reagents:
Mobile Phase: Acetonitrile :Methanol : Solution A = (900 : 300 : 800)
Preparation of Solution A:
4.40 g of Dibasic Potassium Phosphate and 500 mg 1- Octane sodium salt dissolve in 1000 ml water. Adjust pH 8.2 with phosphoric acid.
Diluents: Methanol : Acetonitrile : Solution B = (700 : 600 : 700)
Preparation of Solution B:
1.7 g monobasic ammonium phosphate dissolve in 1000 ml of water, adjust pH 10.0 with ammonium hydroxide.
Standard Preparation:
Transfer about 20 mg of Azithromycin dihydrate WS, accurately weighed, in a 50 ml volumetric flask.
Add 30 ml diluents, shake and sonicate for few minutes to dissolve. Volume with same solvent. Finally filter through 0.2µm of filter trip.
Sample Preparation:
Transfer 500 mg of Azithromycin equivalent powder (about 920mg) in 250 ml volumetric flask, add 120 ml diluents, shake and Sonicate for few minutes. Allow to cool and volume with same solvent. Filter through what man # 41 filter paper and take 5 ml to 25 ml volumetric flask and volume with diluents.
Chromatographic system specifications:
Column : C18
Flow rate : 2.0 ml/minute.
Wavelength : 210 nm.
Temperature : 50° C
Injection volume : 20 µl.
Run time : 25 minutes.
Test Procedure:
Separately weight equal volume (20µl) of the standard preparation and the sample preparation into the chromatograph. Record the chromatograms and measure the responses for major picks andcalculate the content of Azithromycin.
Calculation:
alculation formula as (%) =
Peak area of Spl X dilution of Std X Standard potency (%) X Avg. Weight X 100
Peak area of Std X dilution of Spl X 500 X 100
Label claim X % of Result
Calculation Formula Azithromycin Content/Tablet = mg.
Percentage(100)
Reference: BP (British Pharmacopoeia) Analysis of Azithromycin Tablet
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Abdus Sobhan Salim is professional experienced pharmacist in pharmaceuticals, author and founder of pharmabossbd.com, the first Bangladeshi pharmaceutical blogger since 2019.
