MFR of Betahistine 16 mg Tablets

MFR of Betahistine 16 mg Tablets

TABLE OF CONTENTS

 

S.NO.TITLEPage No
1.0PRODUCT DETAILS02 of 05
2.0MANUFACTURING FORMULA02 of 05
3.0LIST OF EQUIPMENTS02 of 05
4.0MANUFACTURING INSTRUCTIONS02 of 05
5.0GENERAL PRECAUTIONS02 of 05
6.0MANUFACTURING PROCESS DETAILS03 to 05

 

1.0 PRODUCT DETAILS:

Product NameBetahistine Tablets
Product DescriptionWhite color round shape, uncoated tablet having one side mid break line
Strength16 mg
Label claim

 

Each uncoated tablet contains:

Betahistine Dihydrochloride IP -16 mg

Batch Size1,00,000 Tablets
Average Weight120 mg
Shelf Life24 months
StorageStore in a cool, dry and dark place below 250C.
Drug CategoryAnti-vertigo

2.0 MANUFACTURING FORMULA:

Material NameGradeCategoryQuantity per Unit (In mg)Batch Qty.

 (In kg)

Dry Mix
Betahistine Dihydrochloride IPIPAPI16.30 mg1.630 kg
MCCP PH -102IPDiluent81.60 mg8.160 kg
Binder
Ethyl Cellulose IPIPBinder0.1 mg0.010 kg
IPAIPSolvent0.03 ml3.000 Lt.
Lubricant
MCCP PH – 112 IPIPDiluent14.0 mg1.400 kg
Aerosil IPIPGlidant2.00 mg0.200 kg
Talcum IPIPAnti-caking agent5.00 mg0.500 Kg
Magnesium Stearate IPIPAnti- Adherent1.00 mg0.100 Kg

3.0 LIST OF EQUIPMENT’S:

Sr. No.Machinery/equipmentCapacityEquipment ID.
1.Weighing Balance300 kgSC/PD/WBL/01

SC/PD/WBL/02

2.Sifter (with SS Sieves No’s 14, 24, 30 and 60)30”SC/PD/SFT/01

SC/PD/SFT/02

3.Mass Mixer with propeller100 literSC/PD/MSM/01

SC/PD/MSM/02

4.Stirrer for binder preparationSC/PD/STR/01

SC/PD/STR/02

5.Octagonal Blender65 literSC/PD/GR/OB/03
6.Tray Dryer48 TraysSC/PD/TRD/01

SC/PD/TRD/02

SC/PD/TRD/03

SC/PD/TRD/04

7.Halogen Moisture BalanceSC/QC/007
8.Compression Machine35 StationSC/PD/COM/02

SC/PD/CPM/06

9.Poly-lined Containers with lid30 liter (01 No’s) and

45 liter (01 Noes)

           —
10.SS Containers with lid10 liter (4 No’s) and

20 liter (3 Noes)

SC/PD/SST/010

SC/PD/SST/065

11.Filter Cloth 100 No.0.5M

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:
Material Name Std. Qty. (kg)Sieve No.
Dry Mix
Betahistine Dihydrochloride IP1.630 kg24≠
MCCP PH -1028.160 kg40≠
Lubricant
MCCP PH – 112 IP1.400 kg30≠
Aerosil IP0.200 kg14≠
Talcum IP0.500 Kg60  ≠
Magnesium Stearate IP0.100 Kg30  ≠
  • 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 35o in Tray Dryer until the LOD of granules is between 1.0 to 1.5% at 105oC checked by Halogen Moisture Balance.
  • Drying Time: 3 to 4 hours.
  • Drying Temperature: 35oC
  • 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:
TestSpecification
Appearance of blend

Blend Uniformity

Blend Assay

LOD

Bulk Density

Tapped Density

Compressibility Index

Hausner Ratio

White free-flowing granular powder

90% to 110%

98% to 103 %

1.0% to 1.5%

To be established in next batch

To be established in next batch

To be established in next batch

To be established in next batch

 

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.
S.

No.

ParametersStandardNo. of TabletsIn-Process Frequency
1.       Feed frame alignment and adjustmentShould be satisfactory—–—–
2.       Lower Weight AssemblyShould be satisfactory—–—–
3.       Hydraulic Pressure

 

5-6 Tones (B-Tooling, 35 stations Compression Machine)—–—–
4.       Machine Speed18 RPM- 22 RPM—–—–
5.       Punch Size6.5 mm—–—–
6.       Upper Punch6.5 mm with brake line—–—–
7.       Lower Punch6.5 mm—–—–
8.       Die6.5 mm—–—–
9.       Average – Diameter6.5 mm6/Individual2 hours
10.   Thickness2.5 mm ±.2 mm6/Individual2 hours
11.   Weight of 20 Tabs.2.400 g ± 2%20/Composite30 minutes
12.   Uniformity of WeightNMT 2 tablets out of 20 deviate from the average weight by more than 3%. No tablet deviates from the average weight by more than 5%—–01 hour
13.   Average Weight of Tablets120 mg ± 2%20/Individual30 minutes
14.   HardnessNLT 2.5 kg/cm26/Individual30 minutes
15.   Disintegration TimeNMT 10 min6/Composite01 hour
16.   FriabilityNMT 1%20/Composite01 hour

 

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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