MFR of Betahistine 16 mg Tablets

TABLE OF CONTENTS

1.0 PRODUCT DETAILS:

2.0 MANUFACTURING FORMULA:

3.0 LIST OF EQUIPMENT’S:

4.0 MANUFACTURING INSTRUCTIONS:

• All the manufacturing activities shall be performed under controlled conditions (temperature NMT 25 ⁰C and relative humidity NMT 45 %).
• When working with Active Ingredients and drug product or mixture of Active Ingredients and Excipients, wear gloves and mask to avoid exposure and contact with any body parts.

5.0 GENERAL PRECAUTIONS:

• Before working with Betahistine Hydrochloride, read Material Safety Data Sheet of Active Ingredients.
• In case of skin contact (Irritants), wash skin with soap and water for at least 15 minutes. Cold water may be used.
• To protect the eyes, use goggles and in case of infection wash the eyes thoroughly with running water.
• General reported side effect:Feeling Sick (Nausea), Indigestion, Headache, Allergic skin reactions such as Itching and Rash.

• MANUFACTURING PROCESS DETAILS:

6.1 GRANULATION:

STEP – I (SIFTING):

• Check Sieve Integrity (before sifting and after sifting).
• Set the Sifter and sieve the dispensed materials as per Sieve Sizes mentioned below:

• Geometrically mix Betahistine Dihydrochloride IP (1.630 kg) with MCCP PH-102 IP (8.160 kg) before sifting.
• Collect sifted Betahistine Dihydrochloride IP and MCCP PH -102 in SS Container (capacity: 20 liter).
• Collect sifted MCCP PH – 112 IP,Aerosil IP and Talcum IP in SS Container (capacity: 10 liter).
• Collect the sifted Magnesium Stearate IP in SS Container (capacity: 10 liter).

STEP –II (DRY MIXING):

Transfer the sifted Betahistine Dihydrochloride IP (1.630 kg) and MCCP PH- 102 IP (8.160 kg.) in Mass Mixer (capacity: 100 liter) and dry mix the materials till uniform mixing.

Mixing Time: 10 minutes.

Mixing Speed: 36 RPM

Paddle (Blades) Timing & Direction = 5 minutes in clockwise direction & 5 minutes in anti-clockwise direction.

STEP – III (BINDER PREPARATION):

Take IPA (3.000 liter) in SS container (capacity: 10 liters) and add Ethyl Cellulose (0.010 kg.) and mix together with stirrer till dissolved properly in IPA.

Filter it with 100# filter cloth & store in SS container (capacity: 10 liter).

STEP –IV (BINDING OF DRY MIX MATERIAL):

Slowly add the binder of Step-III in dry mix materials of Step-II and mix for 10 minutes till uniform binding and after binding,collect the wet mass in SS Container (capacity: 20 liter).

Mixing Time: 10 minutes

Mixing Speed: 36 RPM

Paddle (Blades) Timing & Direction = 5 minutes in clockwise direction & 5 minutes in anti-clockwise direction

STEP- V (DRYING):

Dry the wet mass of Step -IV as follows:

First air dry the granules for 30 minutes in Tray Dryer. Ensure that heaters at OFF mode during air drying. After air drying, dry the granules at 35^o in Tray Dryer until the LOD of granules is between 1.0 to 1.5% at 105^oC checked by Halogen Moisture Balance.

Drying Time: 3 to 4 Hours.

Drying Temperature: 35^oC

Raking Frequency: After every 15 minutes.

STEP -VI (SIZING/MILLING):

Check Sieve Integrity (before sifting and after sifting).

Sieve the dried material with sieve 40 # manually in Poly-lined SS Container (capacity: 20 liter)

STEP -VII (PRE –LUBRICATION):

Load the milled granules of Step-VI in Octagonal Blender and add sifted MCCP-PH-112 IP (1.4 kg), Aerosil IP (0.200 kg.) and Talcum IP (0.500 kg) and mix properly till uniform mixing of Pre-Lubricating material.

Mixing Time: 20 minutes. (10 minutes clockwise direction &10 minutes anti-clockwise direction)

Mixing Speed: 10 RPM

STEP – VIII (LUBRICATION):

Add the sifted Magnesium Stearate IP (0.100 kg.) in the Pre-Lubricated Material of Step-VII and mix properly till uniform mixing of materials with Magnesium Stearate is complete.

Mixing Time: 05 minutes. (clockwise direction)

Mixing Speed: 10 RPM

STEP- IX (BLEND SAMPLE ANALYSIS):

After completion of lubrication, collect the composite blend sample and send to QC for analysis according to the table below:

STEP – X

Unload the above blended material in one Poly-lined HDPE Containers (capacity: 45 liter).

STEP – XI

Clean all equipments used in the granulation as per respective equipment cleaning SOP.

• COMPRESSION:

STEP -I

After receiving QC approval for blend, compress the blend as per the following parameters and In-Process checks under controlled environmental condition.

STEP – II

Send the sample of compressed tablets to QC department for analysis.

STEP – III

Weight the compressed tablets and store into one Poly-lined HDPE Container with lid (capacity: 30 liter) with proper status label till next step tablet packing.

STEP – IV

Cleanthe Compression Machine as per cleaning SOP.

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