Tablet Break-line Study: Tablet Scoring Study of Azithromycin Tablets 500mg

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. 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.

RESPONSIBILITY

• It is the responsibility of the validation officer to perform the Tablet Splitting as per regulatory guidelines.
• 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	:

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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)

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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.

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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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