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 products or a mixture of Active Ingredients and Excipients, wear gloves and a mask to avoid exposure and contact with any body parts.

5.0 GENERAL PRECAUTIONS:

• Before working with Betahistine Hydrochloride, read the Material Safety Data Sheet of Active Ingredients.
• In case of skin contact (Irritants), wash skin with soap and water for at least 15 minutes. Coldwater 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 liters).
• 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 liters)

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 it to QC for analysis according to the table below:

STEP – X

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

STEP – XI

• Clean all equipment 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 conditions.

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

• Clean the Compression Machine as per cleaning SOP.

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