Cipro - MFR 500r1

FOURRTS (INDIA) LABORATORIES PVT.
LIMITED
PLANT II, Venkatamangalam, Chennai – 600127
MASTER FORMULA RECORD
Department Formulation Development Page 1 of 18
MFR No MFR-103/00 Supersedes no. NA
MFR for Ciprofloxacin 500 mg tablets Effective Date
Master Formula Record

Product : Ciprofloxacin 500 mg tablets
Batch size : 7,50,000 Tablets
Product code: C15T
Prepared by Reviewed by Approved by

FD Department FD Department FD Head QA Head
Sign/date Sign/date Sign/date Sign/date

FOURRTS (INDIA) LABORATORIES PVT.LIMITED
TABLE OF CONTENTS:
S.No. Contents Page No.

1.0 General Information 03
2.0 Bill of materials for product manufacturing 05
3.0 Potency Calculation
06
4.0 Raw Material Storage Condition for batch manufacturing 07
5.0 Equipments/Utilities to be used 08
6.0 Material safety data 09
7.0 Instructions 10
8.0 Process Flow Diagram 11
9.0 Manufacturing / Processing Area Environment Conditions 12
10.0 Manufacturing procedure 13
11.0 Film Coating 17
12.0 Physical parameter of Film Coated Tablet 17
13.0 Inspection 18
14.0 Storage instructions 18
15.0 Attachment to the MFR 19


1.0.General Information
1.1 Generic Name Ciprofloxacin 500 mg tablets
1.2 Type of formulation Film coated tablet
White to creamish white capsule shaped film coated tablets debossed
1.3 Product description
“CPR500” with breakline one side and “BL” on the reverse.
1.4 Product Code C15T
1.5 Product licence PL17907/0015
1.6 Shelf life 48 months
Optimization Batch Record – IM19CB/OB/001, C15T/OB/001
1.7 Reference Documents
Process Optimization Protocol – FD/PRO/POP-054
Each film coated tablet contains: Ciprofloxacin hydrochloride EP
1.8 Label Claim
equivalent to Ciprofloxacin 500mg
Proposed Market /
United kingdom / Bristol
1.9 Customer
1.10 Product related information

Pharmacotherapeutic Second generation fluoroquinolone antibiotic (Quinolone antimicrobial
classification agent)
Pharmacopoeial status Ph.Eur
Physicochemical properties of API
Ciprofloxacin hydrochloride
Description A pale yellow, crystalline powder
Molecular formula C17H18FN3O3
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic
Chemical name
acid
Molecular Weight 331.347 g/mol
Melting Point 255-257 °C
Molecular Structure
Solubility Soluble in dilute (0.1N) hydrochloric acid; practically insoluble ethanol

Biopharmaceutical Class III


Usual
Infection Severity Dose Frequency
duration
Urinary Tract Acute 250mg Every 12 h 3 days
Mild 250mg Every 12 h 7-14 days
Severe 250mg Every 12 h 7-14 days
Posology and
Chronic Mild/Moderate 500 mg Every 12 h 28 Days
administration
Bacterial
Prostatitis
Lower Mild 500 mg Every 12 h 7-14 days
Respiratory Severe 750 mg Every 12 h 7-14 days
Tract
Mechanism of action The bactericidal action of ciprofloxacin results from inhibition of the enzymes
(brief) topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for
bacterial DNA replication, transcription, repair, strand super coiling repair, and
recombination.
Pharmacokinetic parameters
Rapidly and well absorbed from the gastrointestinal tract after oral
Absorption
administration. The absolute bioavailability is approximately 70% with no
substantial loss by first pass metabolism.
Half life
4 hours
Hepatic. Four metabolites have been identified in human urine which together
Metabolism account for approximately 15% of an oral dose. The metabolites have
antimicrobial activity, but are less active than unchanged ciprofloxacin.
Approximately 40 to 50% of an orally administered dose is excreted in the urine

Elimination
as unchanged drug.
Storage condition Do not store above 25°C. Store in the original package


2.1 Indent of active pharmaceutical ingredient Batch Size: 7,50,000 tablets

Quanti Quantity to be dispensed in Kg
Std Qty/ Qty for
S. Name of active Item ty per
Batch the batch Lot 1 Lot 2 Lot 3
No pharmaceutical ingredient code tablet
(Kg) (Kg)
(mg)
Ciprofloxacin hydrochloride *
1 A064 582.000 436.500 436.500
Ph.Eur
2.2 Indent of excipients
Quanti Quantity to be dispensed in Kg
Std Qty/ Qty for
S. Item ty per
Name of ingredient Batch the batch Lot 1 Lot 2 Lot 3
No code tablet
(Kg) (Kg)
(mg)
Dry mix Materials
1 Maize starch BP/Ph.Eur E030 96.200 72.150 75.757# **
Colloidal Anhydrous Silica

2 E026 3.800 2.850 2.850 0.950 0.950 0.950
BP/Ph.Eur
Binder solution ingredient
3 Purified water Ph.Eur E005 q.s 81.840 83.33 27.770 27.770 27.770
Extra granular materials and Lubrication
Microcrystalline cellulose
4 E132 40.000 30.000 30.000 30.000
PH102 Ph.Eur
Sodium starch glycolate
5 E029 22.800 17.100 17.100 17.100
(Type A) BP/Ph.Eur
6 E026 7.600 5.700 5.700 5.700
BP/Ph.Eur
7 Magnesium Stearate Ph.Eur E016 7.600 5.700 5.700 5.700
Total 760.00 570.000 570.000 -
Coating materials
Hydroxy propyl methyl
8 E161 7.600 5.700 6.840 6.840***
cellulose 15cps BP/Ph.Eur
9 Purified talc BP/Ph.Eur E045 4.560 3.420 4.104 4.104***
10 Titanium dioxide Ph.Eur E020 2.280 1.710 2.052 2.052***
Polyethylene glycol 4000
11 E205 0.760 0.570 0.684 0.684***
BP/Ph.Eur (Macrogol 4000)
12 Purified water BP/Ph.Eur E005 q.s q.s q.s 114.630***
Coated tablet weight 775.200 581.400 581.400 -
* Actual quantity of Ciprofloxacin hydrochloride Ph.Eur to be dispensed based on Actual assay (as is basis) and
Water content.
**The amount of maize starch has to be adjusted to compensate for additional quantity of Ciprofloxacin
hydrochloride Ph.Eur # Does not exist in the final product.
#
5% extra Maize starch added to compensate for loss in moisture of Maize starch after drying
***20% extra coating solution can be taken to compensate losses during coating.


3.0 Calculation:
Calculate the actual quantity of Ciprofloxacin hydrochloride Ph.Eur as per the following formula:
Standard quantity Ciprofloxacin hydrochloride Ph.Eur (If 100% m/m Assay) = kg
Note: If the Assay is greater than 100%, Assay to be rounded to 100% for calculation.
NOTE: If the potency is greater than 100%, potency to be rounded to 100% for calculation.
3.1 Potency Calculation for Ciprofloxacin hydrochloride Ph.Eur:
Quantity of Ciprofloxacin Ph.Eur

required for batch (P) (kg) = Std qty per batch x 100 x 100 ___________________
Assay (on anhydrous basis) x [100 – water content (% w/w)]
P = _____________
In case of Raw material from more than one A.R. No.
From first A.R number:

Available stock quantity (R) = Kg
% w/w assay % w/w Water content
Entered by/date (PR) Verified by / date (IPQA)
(on anhydrous basis) (B1) (C1)
From second A.R number:

% w/w assay % w/w Water content
Entered by/date (PR) Verified by / date (IPQA)
(on anhydrous basis) (B2) (C2)


Quantity to be added from second A.R number (S) =
436.500 – Rx B1 x (100-C1) X 100 x 100____ = ____________ kg

100 x 100 B2 x (100-C2)
Quantity of Ciprofloxacin hydrochloride Ph.Eur to be added from the second AR.No. (S) = _______kg
Total quantity of Ciprofloxacin Ph.Eur to be added for the batch (Q) = R+S = __________kg
3.2 Compensation of maize starch Ph.Eur:
Actual Quantity of maize starch Ph.Eur (T) = (Standard quantity of ciprofloxacin + Standard quantity of maize
starch) – (Quantity of ciprofloxacin to be dispensed) + 5%
T = ______________kg


4.0 Raw Material Storage Condition for batch manufacturing
Specifications and testing

S.No. Materials Storage Condition
requirements
Ciprofloxacin hydrochloride Store below 25º C in an airtight
1 container, protected from light. As per Ph.Eur
Ph.Eur
Protected from light and
2 Maize Starch BP/Ph.Eur As per BP/Ph.Eur
moisture.
3 Store below 25º C As per BP/ Ph.Eur
BP/Ph.Eur
Cellulose microcrystalline Store in tightly
4 As per Ph.Eur
Ph.Eur (Avicel PH102) closed container
Sodium starch glycolate (Type Store in tightly
5 closed container at ambient As per Ph.Eur
A) Ph.Eur
temperature
Store in a tightly closed
6 Magnesium Stearate Ph.Eur As per Ph.Eur
container
7 Hydroxy propyl methyl cellulose Store in a tightly closed

As per Ph.Eur
15cps container, cool and dry place.
8 Store in a well closed container
Titanium dioxide Ph.Eur As per Ph.Eur
below 25°C
9 Store in a tightly closed
Purified talc BP / Ph.Eur As per Ph.Eur
container
10 Polyethylene glycol 4000

Store in tightly closed container As per Ph.Eur
(Macrogol PEG 4000) BP/Ph.Eur


5.0 Equipments/Utilities to be used:
List of equipments used in List of equipments recommended to be used

S.No.
Optimisation batch. in Production.
Electronic balance - 210 g, 220 g, 3.00kg, Electronic balance (210 g, 220 g, 3.00kg,
1 30.00kg, 150.00kg) 30.00kg, 150.00kg, 1500.00 kg)
2 Vibratory sifter (30”) Vibratory sifter (30”)

3 Sieves ( #16,#40, #100 ) Sieves ( #16,#40, #100 )
4 Vacuum cleaner Vacuum cleaner
5 Sifter(100#,40#,16#) Sifter(100#,40#,16#)
6 Cone mill (1.5mm) Cone mill (1.5mm)
7 Steam kettle Steam kettle
8 Rapid mixer granulator (150 L) Rapid mixer granulator (800 L)
9 Fluid bed equipment (125 L) Fluid bed equipment (800 L)
10 Bin blender (300L) Bin blender (1500L)
11 IPC Bin (150L) IPC Bin (1500L)
12 Manufacturing accessories Manufacturing accessories
13 Compression machine 51 station Compression machine 51 station
14 Auto coating machine (600mm) Auto coating machine (1500mm)
15 Inspection machine Inspection machine
16 IPQA Instruments IPQA Instruments
17 Moisture analyzer Moisture analyzer
18 Required Accessories
Scoops, SS vessels, SS spoons, HDPE containers and poly bags.


6.0 Material Safety Data
6.1 Ciprofloxacin Hydrochloride

Handling precautions Hazard identification First Aid measures
Avoid contact with eyes. Avoid Health Effects: Eye Contact: Flush eyes with
prolonged repeated skin contact Acute toxicity –category -4(oral/dermal) plenty of water for at least 15
and breathing dust /powders. Eye irritant –category 2B minutes ,occasionally lifting the
Handling: Wash thoroughly after Mutagenicity-No information found upper and lower eyelids. Get
handling. Use the adequate Carcinogenicity Effects: No information. medical aid.
ventilation. Minimize dust Found reproductive /Developmental – Skin Contact:
generation and accumulation. Category 2 Get medical aid Flush skin with
Avoid contact with eyes, skin, Target organ toxicity(repeated) –Category- plenty of soap solution and
and clothing. Keep container 3 water atleast 15 minutes after
tightly closed. Avoid ingestion Environmental: Chronic aquatic toxicity- removing contaminated
and inhalation. chronic category -4 clothing and shoes. Wash
Store in a tightly closed container . contaminated cloths before
reuse.
Ingestion: Never give anything
by mouth to an unconscious
person. Get medical aid. Do not
induce vomiting. If conscious
and alert, rinse mouth and drink
2-4 cupfuls of milk or water.
Inhalation: Remove the
inhaled person from exposure
to fresh air immediately. If not
breathing, give artificial
respiration. If breathing is
difficult, give oxygen. Get
medical aid.
7.0 Instructions
7.1 Carefully read and follow all manufacturing instructions.

7.2 Clean all equipment as per prescribed SOP and operate as per prescribed Work Instruction.
7.3 Check and confirm each area is cleaned as per relevant SOP.
7.4 Wear prescribed garments, hand gloves, mouth mask at every processing stage.
7.5 Conduct in-process check for parameters mentioned and take corrective steps as required.


8.0 PROCESS FLOW DIAGRAM

Dispense all the raw materials as
Stage 1: Dispensing
per the manufacturing formula
provided.
Sifting Stage 2: Sifting

Ciprofloxacin hydrochloride (Equipment: Vibro Sifter)
Ph.Eur # 16 mesh, Maize starch
Ph.Eur #100 mesh and Colloidal
Anhydrous silica Ph.Eur # 40 Stage 3: Granulation – Dry mixing
Extra granular addition (Equipment: RMG 800L)
Sodium starch glycolate Ph.Eur, Load the Sifted Ciprofloxacin hydrochloride
Cellulose microcrystalline Ph.Eur, Maize starch Ph.Eur and Colloidal
Ph.Eur, Colloidal Anhydrous Anhydrous silica Ph.Eur in RMG and mix for
silica Ph.Eur and Magnesium 20 minutes at slow speed /Chopper off
Stearate BP/Ph.Eur through # 40
mesh Stage 3.1: Granulation – wet mixing
(Equipment: RMG 800L)
Binder Addition: Split the purified water into
2 equal half. Add first half of purified water
is added slowly into dry mix through Granulation fluid:
sprinkler for 2 minutes at Impeller-Slow 27.770 Kg Purified water
BP/Ph.Eur (Previously boiled
and chopper fast, then open the lid rack
and cooled)
properly to get uniform mass. And add
second half of purified water in to RMG for
2 minute
Stage 4: Sizing (Co-mill) 10 mm Drying parameters

screen Inlet temperature: 60 - 70°C
Exhaust temperature: NMT
Stage 5: Drying (Equipment: FBE) 45°C
Product temperature: NMT
38°C
Dried granules sifted through 16# and Stage 6: Sizing & Milling Blower drive: NMT 100%
retentions milled through 1.5mm (Equipment: Vibro sifter and cone mill) LOD: NMT 4.0 % w/w
screen.
Stage 7: Blending (1500 L IPC Bin)

Load the sized and sifted granules into the IPC bin and blend for 5minutes at 5 RPM
Add the sifted Sodium starch glycolate Ph.Eur, Cellulose microcrystalline Ph.Eur, Colloidal
anhydrous to the above blend and mix for 10min at 5 RPM.
Stage 8: Lubrication
Add the sifted Magnesium stearate into the IPC bin and mix for 2 minutes at 5 RPM

Cont…
500mg tablets
Average weight - 760.00mg ± 5%
Thickness - 5.0 – 5.4 mm
Hardness - NLT 110N
Friability - NMT 1.0%
Stage 9: Compression Disintegration time- NMT 15min
(51 Station compression machine) Speed - 15-25RPM
Disintegration time – NMT

15min
Acceptance criteria Stage 10: Coating Coating Parameters**
Average weight : 775.2 ± 5% Preheating : NMT 45°C
Weight gain : 15.2 mg/tablet Inlet temp : 65± 10°C
Disintegration : NMT 30mins Exhaust air temp : 40 - 50°C
Bed temperature : 35 - 45°C
Pan motor : 3 - 8 rpm
Stage 11: Packing
Spray rate : 10 – 60 g/min/gun
No. of spray gun : 6
Atomization air : 1.5- 4.0 kg/cm2
Pressure
9.0 Manufacturing / Processing Area Environment Conditions

Area Temperature Relative Humidity
Dispensing Area NMT 25°C NMT 65% RH
Granulation area NMT 25°C NMT 65% RH
Blending area NMT 25°C NMT 65% RH
Compression NMT 25°C NMT 45% RH
Coating NMT 25°C NMT 65% RH
Inspection NMT 25°C NMT 65% RH
Packing NMT 25°C NMT 65% RH


10.0 Manufacturing procedure

Safety precautions: Wear 3M nose mask and goggles before entry to the area.
10.1 Dispensing
10.1.1 Dispense all the material as per the BOM using calibrated balances.
10.2 Sifting
Sift Ciprofloxacin Hydrochloride through #16 mesh and Maize starch through 100# and Colloidal
10.2.1
silicon dioxide through #40mesh collect in a double lined polyethylene container with separate label
Sift Microcrystalline cellulose Ph.Eur, Sodium starch glycolate, colloidal silicon dioxide and
10.2.2
Magnesium stearate Ph. Eur through #40 mesh and collect in a separate labeled container.
10.2.3 Check and record the sieve integrity before and after sifting.
10.3 Dry mixing
Load the sifted Ciprofloxacin Hydrochloride, Maize starch and Colloidal silicon dioxide into RMG.
10.3.1 Ensure the discharge valve is closed at the time of material charging. Mix the charged materials with
impeller in ‘Slow’ speed and chopper ‘off’ for 20 minutes.
10.3.2 Record the impeller speed and duration of dry mixing in batch processing record.
10.4 Granulation fluid
Take approximately 27.770 kg of Purified water (previously boiled and cooled) and split into 2 lots and
10.4.1
kept aside in cleaned vessel.
10.5 Wet granulation
Add first half Binder solution of step no.10.4.1 through Sprinkler to RMG containing dry mix materials
of pt.no.10.3.1 with impeller slow and chopper fast up to 2 minutes. Open the lid, rack properly for
10.5.1 uniform mixture, and continue addition of second half granulation fluid into RMG with impeller slow
and chopper fast up to 2 minutes. After complete addition of solution, knead for 1 minute at impeller
fast and chopper fast. Monitor and record the amperage value.
Continue mixing for further time with slow speed till granulation end point reached. If required use
10.5.2
previous boiled and cooled Purified water in increments of 0.500L
Determination of End point:
Precaution: Use hand gloves for this test
10.5.3 Procedure: Take one handful of wet mass and press to form a lump, open the palm and break the lump
by pressing the thump at the centre of the lump
Observation: The lump should break into small pieces
Record all the in-process parameters like impeller and chopper speeds, Granulation fluid addition time,
10.5.4 actual wet granulation time, additional quantity of purified water and the Ampere reading of impeller
obtained after completion of granulation in batch processing record.
Unload the wet granulated mass in FBE Bowl by opening the RMG discharge valve at impeller slow
10.5.5
with 10mm screen attached.
Repeat above process for another 2 lots of dry mix
10.6 Drying
Transfer the wet mass into the FBE bowl. Switch on FBE and dry the wet granules at following set
parameters
10.6.1
Inlet temperature: 60-70°C
Product temperature : NMT 38°C

Exhaust temperature: NMT45°C
Blower drive : NMT 100 %
Initially air dry the FBE bowl for 10 minutes and Carry out the drying as per the condition
10.6.2
mentioned above and rack the material every 15minutes to get uniform drying process.
LOD limit: NMT 4% w/w at 105°C in IR moisture analyzer.
10.7 Sifting and milling of dried granules

Sift the dried granules through #16 mesh and mill the retains (if any) using cone mill fitted with 1.5
10.7.1
mm screen at medium speed.
10.7.2 Sift the milled granules through #16 mesh and mill retains of #16 mesh through 1.5mm screen
Observe the milled granules visually. Check and record the LOD and description of the milled
10.7.3
granules and load the milled granules in IPC.
10.7.4 Verify and record all the integrity of screens and sieves before and after use.
10.7.5 Verify and record the yield of sized granules in Batch Processing Record.
10.8 Pre- Lubrication
10.8.1 Load the sifted and sized granules into the Blender and mix for 5minutes at 5 RPM
Load the sifted quantity of Microcrystalline cellulose Ph.Eur, Sodium starch glycolate, colloidal
10.8.2
silicon dioxide into the above step 10.8.3 and mix for 10 minutes at 5 RPM into IPC bin.
10.8.3 Lubrication: Transfer weighed and sifted quantity of magnesium stearate into blender.
10.8.4 Mix for 2 minutes at 5 RPM speed of blender.
10.8.5 Verify and record the yield of sized granules in Batch Processing Record.
10.8.6 Bulk density of granules : 0.66 g/ml Tapped density: 0.89 g/mL (For information only)
10.9 COMPRESSION
10.9.1 Set up and operate the compression machine & metal detector as per their respective SOP.
10.9.2 Check the upper Punch, Lower Punch and dies before starting the Machine for the correctness.
Compress the lubricated blend in 51 – Station compression machine.
10.9.3
Machine speed 15-25 rpm (optimum- 25rpm)
Punches:
Upper punch : 18.5 x 7.5 mm capsule shaped with breakline and “CPR & 500” embossing on either
10.9.4
side of breakline
Lower Punch: 18.5 x 7.5 mm, capsule shaped with “BL” embossing.
Die: 18.5 x 7.5 mm capsule shaped


10.11 In-process specification and frequency of testing

Recommended No of Equipments to be
S.No. Parameters Specification Frequency tablets to used
PR/IPQA be checked
White to creamish white
capsule shaped, uncoated
Every 60 min / NA
1 Appearance tablets debossed “CPR500” 51
120 min
with breakline on one side and
“BL” on the reverse.
Weight of 20 15.200 g ± 3.0% (14.74 – Every 30 min / 220 g analytical
2 20
tablets 15.65 g) 120 min balance
760.00 mg ± 3.0% (737.20 – Every 60 min / 220 g analytical
3 Average weight 20
782.80mg) 120 min balance
Uniformity of NMT 2/20 to exceed ±5.0% Every 60 min / 220 g analytical
4 20
weight and none then exceed ±10% 120 min balance
Every 30 min / Vernier caliper
5 Thickness 5.0 - 5.4mm 5
120 min
NLT 110 N (Target 150N and Every 30 min/ 5 Hardness tester
6 Hardness
above) 120min
Every 30 min/ Vernier caliper
7 Dimension 18.5 x 7.5 mm ± 0.2mm 5
120min
Disintegration Every 4 hours / Disintegration Tester
8 NMT 15 minutes 6
time Once in shift apparatus
Every 60 min/
9 Friability Not more than 1.0 % w/w 10 Friability Tester
120min
11.0 Film coating

11.1 Preparation of coating solution
11.1.1 Operate the stirrer as per the SOP.
11.1.2 Transfer 114.630 kg of Purified water in SS container.
Disperse HPMC into it, then add purified talc, titanium dioxide and polyethylene glycol one by one to
11.1.3
above solution under stirring and stir for approx 5 minutes after each addition.
11.1.4 Then stir the above solution for approx. 10 minutes.
Homogenize for further approx. 30minutes before and continue stirring during film coating. Filter the
11.1.5
coating solution through #100 mesh.
11.2 Method of film coating
Transfer the approved tablets into pan of auto coater. Set the pan and spray parameters at optimum
11.2.1
level. Coat the tablets with coating solution with optimum parameters given below.
11.2.2 Charge the coating fluid into the solution-holding tank and close the tank.


11.3 Coating Process instructions

11.3.1 Connect the silicon tube between peristaltic pump, spray gun assembly and solution holding tank.
11.3.2 Check spray rate and spray pattern
11.3.3 Check and ensure the pressure differential between coating area and coating pan.
11.3.4 Adjust the distance between tablet bed to spray gun by 15 to 30cm
Before start the coating process, dry the core tablets at an inlet air temperature of 60°C while jogging
11.3.5
the pan with optimum RPM for 5 minutes.
Set the coating parameters as given below
PARAMETERS SET VALUE
Inlet air temperature 65±10°C
Exhaust air temperature 40 - 50°C
Bed temperature 35 - 45°C
Pan motor speed 3 - 8 RPM
11.3.6
Distance between spray gun to tablet bed 15 - 30 cm
Spray rate 10 - 60 g/min/gun
No. of Spray guns 6
Atomizing air pressure 0.5 – 3.0 Kg/cm2
Carry out the coating operation until the weight build up of 15.2 mg (2.00 %) per tablet for 500 mg and
11.3.7
maintain coating parameters as detailed above till the completion of coating operation.
11.3.8 Check and record the weight build up whenever required.
After completion of coating, dry the tablets to room temperature at an inlet air temperature of 40°C
11.3.9
while jogging the pan with 1-2 RPM for 15 – 20minutes.
Allow the tablets to cool at room temperature for 10 minutes by inching the pan continuously before
11.3.10
unloading the tablets.
12.0 Physical parameter of Film Coated Tablet

S.No. Parameters Specification
White to creamish white capsule shaped film coated tablets debossed
1 Description
“CPR 500” with a breakline one side and “BL” on the reverse.
Target weight of coated
2 775.2 ± 3% (751.94 – 798.45 mg)
tablet
3 Weight of 20 tablets 15.504 ± 3% (15.038 – 15.969g)
4 Weight build up 15.2 mg per tablet
5 Disintegration time NMT 30min


14.0 Inspection
14.1 Inspect the tablets for capping, chipping, picking, sticking and black spot on the tablets.
14.2 Any other predominant changes in the tablets.
15.0 Storage Instructions

Stage Container and labeling Area and Condition of storage
Store in granule hold area
Blended Store in IPC bins; label each container with B. No. details,
(Temperature: NMT 25°C and RH:
Granules weight and container Number.
NMT 65%)
Store in HDPE containers with double polythene bag lined Store in hold for coating area
Core
and tightly closed & label each container with B. No. details, (Temperature: NMT 25°C and
Tablets
weight and container Number. RH: NMT65%)
HDPE containers with double polythene bag lined, tightly Store in hold for inspection area
Coated
closed and label each container with B. No. details, weight (Temperature: NMT 25°C and
tablets
and container Number RH: NMT 65%)
Store in Tablet/capsule hold for
HDPE containers with double line polythene bag, tightly
Inspected packaging area
closed and label each container with batch number details,
tablets (Temperature: NMT 25°C and
weight and container number.
RH: NMT 65%)
16.0 MFR Attachments
S. No. Title Document No.

1 Bill of materials
2 Blend Specification
3 In process specification
4 Bulk product specification
5 Finished product specification
6 Blend standard test procedure
7 In process standard test procedure
8 Bulk product standard test procedure
9 Finished product standard test procedure
10 Cleaning validation standard test procedure




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FOURRTS (INDIA) LABORATORIES PVT.

Master Formula Record

Batch size : 7,50,000 Tablets

Product code: C15T

Prepared by Reviewed by Approved by

Sign/date Sign/date Sign/date Sign/date

S.No. Contents Page No.

Prepared by Reviewed by Approved by

Sign/date Sign/date Sign/date Sign/date

1.10 Product related information

Solubility Soluble in dilute (0.1N) hydrochloric acid; practically insoluble ethanol

Prepared by Reviewed by Approved by

Sign/date Sign/date Sign/date Sign/date

Approximately 40 to 50% of an orally administered dose is excreted in the urine

Prepared by Reviewed by Approved by

Sign/date Sign/date Sign/date Sign/date

2.1 Indent of active pharmaceutical ingredient Batch Size: 7,50,000 tablets

Colloidal Anhydrous Silica

Prepared by Reviewed by Approved by

Sign/date Sign/date Sign/date Sign/date

Standard quantity Ciprofloxacin hydrochloride Ph.Eur (If 100% m/m Assay) = kg

3.1 Potency Calculation for Ciprofloxacin hydrochloride Ph.Eur:

Quantity of Ciprofloxacin Ph.Eur

In case of Raw material from more than one A.R. No.

From first A.R number:

From second A.R number:

Prepared by Reviewed by Approved by

Sign/date Sign/date Sign/date Sign/date

Quantity to be added from second A.R number (S) =

436.500 – Rx B1 x (100-C1) X 100 x 100____ = ____________ kg

3.2 Compensation of maize starch Ph.Eur:

Prepared by Reviewed by Approved by

Sign/date Sign/date Sign/date Sign/date

Specifications and testing

7 Hydroxy propyl methyl cellulose Store in a tightly closed

10 Polyethylene glycol 4000

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5.0 Equipments/Utilities to be used:

List of equipments used in List of equipments recommended to be used

2 Vibratory sifter (30”) Vibratory sifter (30”)

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6.0 Material Safety Data

6.1 Ciprofloxacin Hydrochloride

7.1 Carefully read and follow all manufacturing instructions.

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8.0 PROCESS FLOW DIAGRAM

Sifting Stage 2: Sifting

Stage 4: Sizing (Co-mill) 10 mm Drying parameters

Stage 7: Blending (1500 L IPC Bin)

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Disintegration time – NMT

9.0 Manufacturing / Processing Area Environment Conditions

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10.0 Manufacturing procedure

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10.7 Sifting and milling of dried granules

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436.500 – Rx B1 x (100-C1) X 100 x 100 = ________ kg