SOP for Forced Degradation Study

OBJECTIVE

To provide the procedure for the Forced Degradation Study

SCOPE

This procedure is Applicable to the Forced Degradation Study in PharmaInfo Ltd.

RESPONSIBILITY

QC-Chemist

ACCOUNTABILITY

Executive – Quality control

Head – Quality control

PROCEDURE

Forcibly degrade the sample under elevated temperature, photodegradation, at 75% relative humidity, water hydrolysis, acid hydrolysis, base hydrolysis, and oxidation. This is an example of Pregabalin.

1. Thermal Degradation

• Take about 5.0 grams of sample and forcibly degrade it at 60°C temperature for 10 days. Collect about 1.0gm of sample on the 1st day, 3rd day, 5th day, and 10th day. Check the purity.
• If the sample is not analyzed immediately the same sample can be stored in a freezer and it can be analyzed later.

2. Photo Degradation

• Take about 5 grams of the sample and forcibly degrade the sample under UV light at 254 nm.
• Initially collect about 0.5 gm of the sample after 3 hours. Check the purity. Based on the results, either it can be stopped or continued for up to 10 days. If continued for 10 days collect 0.5 grams of sample on the 18th day, 3rd day, 5th day, and 10th day. Check the purity.
• If the sample is not analyzed immediately the same sample can be stored in a freezer and it can be analyzed later.

3. Degradation @75% Relative Humidity

Take about 5.0 grams of sample and forcibly degrade it at 75% Relative Humidity for 10 days. Collect about 1 gram of sample on the 1st day, 3rd day, 5th day, and 10th day. Check the purity. If the sample is not analyzed immediately the same sample can be stored in a freezer and it can be analyzed later.

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4. Water Hydrolysis

• Forcibly degrade the sample using water at room temperature. Based on dissolution, change the medium. Initially collect 10 mL of sample after one hour and check the purity. Based on the results either it will be stopped or continued up to 48 hours. 
• It will be stopped whenever the sample meets the degradation limit defined at the end of this protocol. If the sample is not analyzed immediately the same sample can be stored in a freezer and it can be analyzed later.

5. Acid Hydrolysis

• Forcibly degrade the sample using 0.5 N HCI at room temperature.
• Preparation of 0.5N HCl: Take 42.5 mL of Hydrochloric Acid into a 1000 mL Volumetric flask dissolve it in 100ml of Water make upto the mark with water and mix well.
• Initially collect 10 mL of the sample after one hour. Check the purity. Based on the results, either it will be stopped or continued for up to 48 hours. It will be stopped whenever the sample meets the degradation limit defined at the end of this protocol.
• If the sample is not analyzed immediately the same sample can be stored in a freezer and it can be analyzed later.

6. Base Hydrolysis

• Forcibly degrade the sample using 0.5 N NaOH at room temperature.
• Preparation of 0.5N NaOH: weigh accurately 21gms of Sodium Hydroxide into a 1000mL Volumetric flask dissolve in 100mL of Water dilute to volume with water and mix well. Initially collect 10mL of the sample after one hour. Check the purity. Based on the results, either it will be stopped or continued for up to 48 hours. It will be stopped whenever the sample meets the degradation limit defined at the end of this protocol. If the sample is not analyzed immediately the same sample can be stored in a freezer and it can be analyzed later.

7. Oxidation

• Forcibly degrade the sample using 3 % H202 at room temperature.
• Preparation of 3% H202: Take 100mL of 30% H202 into a 1000mL volumetric flask to it add 100mL of water mix well and dilute to volume with water and mix well.
• Initially collect 10mL of the sample after one hour. Check the purity. Based on the results, either it will be stopped or continued for up to 48 hours. It will be stopped whenever the sample meets the degradation limit defined at the end of this protocol. If the sample is not analyzed immediately the same sample can be stored in a freezer and it can be analyzed later.

Acceptance Criteria:

Specification limit: Degraded percentage should be 5 to 20 %.

ANNEXURE

Nil

REVISION HISTORY

Nil

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