MFR of Betahistine 16 mg Tablets

TABLE OF CONTENTS

 

S.NO. TITLE Page No
1.0 PRODUCT DETAILS 02 of 05
2.0 MANUFACTURING FORMULA 02 of 05
3.0 LIST OF EQUIPMENTS 02 of 05
4.0 MANUFACTURING INSTRUCTIONS 02 of 05
5.0 GENERAL PRECAUTIONS 02 of 05
6.0 MANUFACTURING PROCESS DETAILS 03 to 05

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1.0 PRODUCT DETAILS:

Product Name Betahistine Tablets
Product Description White color round shape, uncoated tablet having one side mid break line
Strength 16 mg
Label claim

 

Each uncoated tablet contains:

Betahistine Dihydrochloride IP -16 mg

Batch Size 1,00,000 Tablets
Average Weight 120 mg
Shelf Life 24 months
Storage Store in a cool, dry and dark place below 250C.
Drug Category Anti-vertigo

2.0 MANUFACTURING FORMULA:

Material Name Grade Category Quantity per Unit (In mg) Batch Qty.

 (In kg)

Dry Mix
Betahistine Dihydrochloride IP IP API 16.30 mg 1.630 kg
MCCP PH -102 IP Diluent 81.60 mg 8.160 kg
Binder
Ethyl Cellulose IP IP Binder 0.1 mg 0.010 kg
IPA IP Solvent 0.03 ml 3.000 Lt.
Lubricant
MCCP PH – 112 IP IP Diluent 14.0 mg 1.400 kg
Aerosil IP IP Glidant 2.00 mg 0.200 kg
Talcum IP IP Anti-caking agent 5.00 mg 0.500 Kg
Magnesium Stearate IP IP Anti- Adherent 1.00 mg 0.100 Kg

3.0 LIST OF EQUIPMENT’S:

Sr. No. Machinery/equipment Capacity Equipment ID.
1. Weighing Balance 300 kg SC/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 propeller 100 liter SC/PD/MSM/01

SC/PD/MSM/02

4. Stirrer for binder preparation SC/PD/STR/01

SC/PD/STR/02

5. Octagonal Blender 65 liter SC/PD/GR/OB/03
6. Tray Dryer 48 Trays SC/PD/TRD/01

SC/PD/TRD/02

SC/PD/TRD/03

SC/PD/TRD/04

7. Halogen Moisture Balance SC/QC/007
8. Compression Machine 35 Station SC/PD/COM/02

SC/PD/CPM/06

9. Poly-lined Containers with lid 30 liter (01 No’s) and

45 liter (01 No’s)

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

20 liter (3 No’s)

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 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:
Material Name Std. Qty. (kg) Sieve No.
Dry Mix
Betahistine Dihydrochloride IP 1.630 kg 24≠
MCCP PH -102 8.160 kg 40≠
Lubricant
MCCP PH – 112 IP 1.400 kg 30≠
Aerosil IP 0.200 kg 14≠
Talcum IP 0.500 Kg 60  ≠
Magnesium Stearate IP 0.100 Kg 30  ≠
  • 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 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 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:

 

Test Specification
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 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.

 

S.

No.

Parameters Standard No. of Tablets In-Process Frequency
1.        Feed frame alignment and adjustment Should be satisfactory —– —–
2.        Lower Weight Assembly Should be satisfactory —– —–
3.        Hydraulic Pressure

 

5-6 Tones (B-Tooling, 35 station Compression Machine) —– —–
4.        Machine Speed 18 RPM- 22 RPM —– —–
5.        Punch Size 6.5 mm —– —–
6.        Upper Punch 6.5 mm with break line —– —–
7.        Lower Punch 6.5 mm —– —–
8.        Die 6.5 mm —– —–
9.        Average – Diameter 6.5 mm 6/Individual 2 hours
10.    Thickness 2.5 mm ±.2 mm 6/Individual 2 hours
11.    Weight of 20 Tabs. 2.400 g ± 2% 20/Composite 30 minutes
12.    Uniformity of Weight NMT 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 Tablets 120 mg ± 2% 20/Individual 30 minutes
14.    Hardness NLT 2.5 kg/cm2 6/Individual 30 minutes
15.    Disintegration Time NMT 10 min 6/Composite 01 hour
16.    Friability NMT 1% 20/Composite 01 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

Cleanthe Compression Machine as per cleaning SOP.

By iamraj