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 Noes)	—
10.	SS Containers with lid	10 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 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 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:

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

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.	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 stations Compression Machine)	—–	—–
4.	Machine Speed	18 RPM- 22 RPM	—–	—–
5.	Punch Size	6.5 mm	—–	—–
6.	Upper Punch	6.5 mm with brake 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

Clean the Compression Machine as per cleaning SOP.

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