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Tablet Scoring Study of Azithromycin Tablets USP 500mg (Tablet Breakline Study)

TABLE OF CONTENTS
  1. Introduction
  2. Objective
  3. Responsibility
  4. Working Standard Details & Sample Details
  5. Method of Analysis
  6. Summary
  7. Conclusions

INTRODUCTION
  • Tablets may bear a break mark or break marks and may be subdivided in parts, either to ease the intake of the medicinal product or to comply with the posology. 
  • Patients expect that the split tablet will provide the same quality, safety and efficacy profile as a whole tablet of equivalent dose. In order to ensure that the patient will receive the intended dose, the efficacy of the break-mark(s) must be assessed during the development of the product.

OBJECTIVE
The objective of this study is to demonstrate the functionality of tablet score & investigate the influence of breakability on tablets.


RESPOSIBILITY
  • It is the responsibility of validation officer to perform the Tablet Splitting as per regulatory guideline.
  • The Manager - Q.C, should ensure that methods of analysis are available & that the equipment to be used for analysis is properly working & calibrated & chemicals used for analysis are available.
  • The Q.A. Manager should ensure that the Tablet Splitting should meet the acceptance criteria & maintain records.

METHODOLOGY

Working Standard Used

 AZITHROMYCIN USP

Reference No.

:

 

LOD

:

 

Purity (as is basis)

:

 

Prepared on

:

 

Valid up to

:

 



Sample Used

Name of Sample

:

Azithromycin Tablets USP 500mg

Batch Number

:

 

Manufacturing Date

:

 

Expiry Date

:

 


Tests to be Perform
  1. Uniformity of Mass
  2. Content Uniformity
  3. Dissolution

Method of Analysis

1.   Uniformity of Mass:
  • Take 30 tablets at random, break them by hand and, from all the parts obtained from 1 tablet, take 1 part for the test and reject the other parts. Weigh each of the 30 parts individually and calculate the average mass.
Acceptance Criteria
  • The tablets comply with the test if NMT 1 individual mass is outside the limits of 85% to 115% of the average mass.
  • The tablets fail to comply with the test if more than 1 individual mass is outside these limits, or if 1 individual mass is outside the limits of 75% to 125% of the average mass.

2.   Content Uniformity:

Chromatographic Conditions:
Column: 250 mm × 4.6 mm, C18, 5 µm
Flow Rate: 1.5 mL/minute
Column Temperature: 50°C
Detection Wavelength: 210 nm
Injection Volume: 50 µL
Mobile Phase: Buffer : Acetonitrile : Methanol (40 : 45 : 15, v/v)
Diluent: Solution A : Acetonitrile : Methanol (35 : 30 : 30, v/v)


Buffer Preparation:
  • Dissolve 4.4gm of dipotassium hydrogen orthophosphate & 0.5gm of sodium 1-octane sulfonate in 1000mL of water, adjust pH of solution to 8.20 ± 0.05 with dilute phosphoric acid.
Solution A Preparation:
  • Dissolve 1.7gm of monobasic ammonium phosphate in 1000mL of water, adjust pH of solution to 10.00 ± 0.05 with ammonium hydroxide
Standard Preparation:
  • Transfer about 250 mg of Azithromycin dihydrate SRS, accurately weighed, to a 100 mL volumetric flask. Add 70 mL of diluent, sonicate to dissolve & dilute with diluent to volume & mix. Dilute 1mL of this solution to 25mL with diluent. Filter through 0.45µ PVDF filter.

Sample Preparation:
  • Take a random sample of 10 intact tablets. Break them by hand and take 1 part for the test and reject the other parts. Transfer 1 part in to 100 ml volumetric flask, add 70 ml of diluent & sonicate for 5 minutes, dilute with diluent to volume & mix. Dilute 1mL of this solution to 25mL with diluent. Filter through 0.45µ PVDF filter.
Calculation:
Calculate the percent of assay by using the following formula:
Where,
At = Area of Sample
As = Average Area of Standard solution
Ws = Weight of Standard
Wt = Weight of Half Portion
ATW = Average tablet weight of half portion
P = Potency of Standard

Acceptance Criteria: 
Within the limits of 85 – 115% and relative standard deviation (R.S.D.) should be equal or smaller than 6%.

3.   Dissolution:

Condition:
Medium: Buffer pH 6.0 ; 900 mL.
Apparatus: II ( Paddle )
Speed: 75 RPM
Time: 30 min
Temperature: 37°C ± 0.5°C


Media Preparation:
  • Dissolve 40.8gm potassium dihydrogen orthophosphate in 6L of water & adjusted the pH to 6.0 with dilute sodium hydroxide.
Preparation of diluent:
  • Dissolve about 17.5gm of dibasic potassium phosphate in 1000mL of water, adjust pH of solution to 8.00 ± 0.05 with phosphoric acid. Mix this solution with acetonitrile in the ration of (80:20)
Standard Solution:
  • Weigh 35mg of Azithromycin dihydrate SRS 100mL volumetric flasks, add 70mL of dissolution media to dissolve & dilute with same to volume. Dilute 10mL of this solution to 25mL with diluent.
Sample Solution:
  • Take a random sample of 6 intact tablets. Break them by hand and take 1 part for the test and reject the other parts. Place 900 mL of dissolution medium maintained at 37 ± 0.5°C in 6 dissolution vessels separately & fix in the tablet dissolution bath maintained at 37 ± 0.5°C. fix the paddle to the shaft & bring it into the position. 
  • Place 1 split tablet each into 6 dissolution vessels. Operate the instrument at 75 RPM for 30 minutes. At the end of 30 minutes, withdraw 5mL of sample of the medium & dilute to 10mL with diluent. Filter through 0.45µ PVDF filter.
Chromatographic Conditions:
Column: 250 mm × 4.6 mm, C18, 5 µm
Flow Rate: 1.5 mL/minute
Column Temperature: 50°C
Detection Wavelength: 210 nm
Injection Volume: 50 µL
Mobile Phase: Buffer : Acetonitrile : Methanol (40 : 45 : 15, v/v)

Buffer Preparation:
  • Dissolve about 4.4gm of dipotassium hydrogen orthophosphate & 0.5gm of sodium 1-octane sulfonate in 1000mL of water, adjust pH of solution to 8.20 ± 0.05 with dilute phosphoric acid

Calculation:
Calculate the % of Azithromycin released by using the following formula:
Where,
At = Area of Sample
As = Average Area of Standard
C = Final Concentration of standard
L = Label claim of half Tablet
Dm = Dissolution medium

Acceptance Criteria:
The average of the 12 results is NLT 75%, and no result is less than 60% in 30 minutes.

SUMMARY

Sr. No.

Parameter

Acceptance Criteria

Results

1.

Uniformity of Mass

85 – 115% NMT 1 Tablet,  75 – 125% None

 

2.

Content Uniformity

Within the limits of 85 – 115%

 

RSD should be equal or smaller than 6%.

 

3.

Dissolution

The average of the 12 results is NLT 75%, no result is less than 60% in 30 minutes.

 



CONCLUSIONS
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