B1. Tableting Flashcards
Why do we use the six-sigma process?
use to improve the quality of product and so having a productivity and efficiency of the manufacturing process
what’s the aim of the SS-process?
it is to eliminate defects and reducing variation
What’s the DPMO
is the 3.4 defects per million opportunities, which is the results of using SS-proces
What’s the ad von SS instead of 3 S
the UCL and LCL are within the operation window, whereas in 3-S they are not
What is the DPMO of 3-sigma?
66810
Definition of SS
a methodology for eliminating variability, defects and waste in a product or process
What is the approach in SS
a data-driven approach
How are defects reduce
By six standard deviation between the mean and the nearest specification limits
What are the two methodology of the SS- process?
DMAIC, DMADV
DMAIC?
Define (control chart) , Measure ( plots), Analysis (DoE, FMEA), Improve and Control (CC)
DMADV
Define, Measure, analysis, Design and Validate
What is a statistical process control (SPC)
it is a tool to translate the variation of a process into values
What kind of variation?
Special cause and common cause variation
Special cause variation?
Variation which are larger in magnitude and can be identified
Common cause variation?
Sum of multitude of effects of a complex interaction
control charts are used to
use to analyses variation causes
What are the three zones in CC?
Zone 1: no actions should be taken
Zone 2: Collection of more information
Zone3: Action required
Zone 2 and 3 are, and zone 1
Zone 2 and 3 are Special causes variation
and zone 1 common cause vairation
Of what does a CC consist?
Central line (average values) UCL and LCL
UCL and LCL are set
3-standard deviation, which is only true when the SD is knwon for the giving process
What is a start-up phase?
where data are collected to create CC
Categorization of Data into?
Attribute data and continous data
Which CC are used in continous data?
x-bar, range and s-charts
x-bar and R are
charts use to defined the stability of the process
x-bar and s-chart?
used for checking mean and variation of a process
What is the equation for LCL and UCL for x-bar?
LCL: mean - A3 *sd
UCL: mean+ A3 * sd
What is the equation for LCL and UCL for s-cart?
LCL: B3 *sd
UCL: B4 * sd
Why do we used the anti-biasing constants and on what does it depends?
ULC and LCL are 3-sd from the mean, although the sample size is low
the empirical standard deviation can only be used with high sample size.
it depends on the sample size, used to create the CC
IPC is use for?
Testing of various quality characterist of intermediates and statistical evaluation of results via control chart
MSPC?
multivariate statistical PC
statistical evaluation of process data or by comparison of to histrical data
PAT?
Process analytical technology
Analysis of quality characteristics by PA in real time
IPC and guidline?
No information in the guidlines what has to be tested, how and where and how frequently
What is the product life cycle?
lap phase, pilot phase
validation phase
lap and pilot phase?
Process design, IPC testing
identify CCP and CMA
Defination of OP limits and inprocess monitoring strategies
–> Data Accumulation
Validation phase?
modification of IPC
process qualification
Focus on critical paramater
What are process capability index?
measures the ability of a process to produce output within specification limits
When is a process capable?
when “ almost all” meansurements of a feature produced by the process fall inside the specification limits
what are typical process capability indices?
Cp, Cpk and Cpm
Cp
process mean (scattering of the process results)
limits of Cp?
Cp >1 process meets specification
what’s the benchmark?
Cp > 1.33
When happend if the mean is not centered?
it leads to Cp overestimates process capability
Equation for Cp
Cp= UCL-LCL /6 sd
Cpk is?
adresses data centering, can be positive, zero or negative
What happend if the Cpk is asymmetric?
underestimation of the proces capability
Cpm?
is a measure of the overall process capability
comparing the specification spread to the spread of your process data while taking into accout the deviation from the target value
Shewhart chart?
Singel (raw) data points
not sensitve to small shifts, can easily detect large changes
EWMA chart
exponential weighted moving averages of all prior sample means.
Cusum chart?
cumulative sum of differences
detects small shifts over time
Calibration and validation of charts?
Calibration: statistical analysis of common variation in the process (UCL, LCL)
Validation: test the charts to distinguish common variation from uncommon variation
different between the shewhart and EWMA chart
Shewhart is not senstve to small shifts, can easily detect larger changes
whereas, EWMA can easily detect small shifts in process means, but not suitable to monitor process variability
Rule of seven?
When 7 points are below or above the limits, assignable cause that needs to be investigated
MSpC is important for?
QA but not the sole indicator of product quality
lean manufacturing
minimizing waste by getting rid of activites that don’t directly generate values for the customer
TIM WOODs?
Transport, Inventory, Motion, Waiting, Overproduction, Overprocessing, Defects
5S?
sort, set in order, shine, standardize, sustain
Poka-Yoke
mistake proofing
elimimation, facilitation, mitigation ( reduce the impact of a failure) and flagging (mak a failure visible)
Tablets machines?
eccentric, rotary or a IMA press
excentre press
disc is fixed excentre
UP–> densification
LP–> fixed during compression
How is the densification on the excentre press?
asymetric, having a sinusidal movement of UP velocity profile
the used of excentre press?
use of high CF, production of larger tablets, more in development and partly veternary tablets production
Rotary press is use for?
for large scale industrial production
Componenen of the RP?
serval punches, stationary hopper, die table (circular die plate or matric table) filling by feed feed frame compression rolls
what’s the feeding sytem in RP
a gravity feeding system with a funnel or force feedig
when do we used the force feeder
at higher tableting speed
what are the circular motion?
compression rolls, the filling and ejection cam
Compression stage in RP?
pre compression, done by small rolls
Main compression densification
how is the compaction process in RP?
it is symmetric
what’s the aim of the pre-compression process
to remove entrapped air, which could lead to capping due to negative binding of the tablet material
How can entrapped air also be remove?
by reducing the tabletting speed
How is the densification process in EP and RP?
densification on the EP is one side, leading to different degrees tablet hardness
what are the CPP in filling?
particle shape, surface and size, which affects the flowability of the tablets material and the density of the particles
Compaction:
Application of pressure with Upper and Lower punch–> particle deformation or fragmentation
Ejection:
overcoming of frictional and adhesion force, elastic recovery
What are the parameter of creating compression force in RP
immersion and fill depth
immersion depth
distance between the punchtips at the maximum compaction pressure.
the final tablet thickness, porosity and hardness is determine by?
immersion depth
how does the ID affects the CF
small ID leads to high CF, higher densification
Fill depth?
influences the tablet mass, depends on the position of the LP
small fill volume leads to
increase of compression force by a deeper immersion depth
when is the force constant ?
For a constant volume at a specified immersion depth
press speed?
number of revolution execute within 1h
TS affects?
affects die filling and dwell time
when can be obtained a constant mass?
when the filling volume is constant
what is the relationship between the tablet weight and thickness?
tablet weight is directly proportion to the tablet thickness
What is the indication of mass variation?
variation of the CF
which 3 parameter are interdependent
tablet weight, thickness and hardness
name of forces during compression
UPF, LPF, die wall, stripping, pressure rollers
type of Displacement?
UP, LP
inductive displacement transducers and incremental displacement
What are some reversible changes during compaction?
Punch compression, die widening and machine fram streching
instrumentation used to control the compression force?
Strain gauge, piezoelectric force transducers and inductive displacement sensor
Strain gauge is a?
metallic conductance track glued onto a puch holder
How CF monitored with strain gauge?
they covert changes in electrical resistance into an electric signal which can be measured.
the electrical resistance changes is proportional to change in length
disad of strain gauges?
they are prone to temeperature changes (friction) wherefor correction factors are necessary
which law is applied?
OHM law
the piezoelectric force transducers
recording the electric potential occuring from a force induced charge shift in the crystal. the shift is then amplified to measure the force
inductive displacement sensor?
detecting the change in alternating-current reistance which is based in the depth dependent movement of the punch into the die
why is the force detection efficient?
due to the proportionality to the tablet mass, meaning that a constant compression force leads to constant tablet mass
how is the proportionality of the Cf and Tw in a strain gauge
the compression is propertional to the voltage measured and therewith for the force applied
which two parameter are proportional to the TM in the strain gauge?
the Cf and voltage for a certain immersion and filling depth
what is the ideal case in strain gauge?
high change in voltage for a small change in mass (higher slope in a voltage-mass-diagram) to adjust the tablet mass precisely
three stages of deformation
elastic, plastic and fragmentation
on what does the deformation depends?
on the applied compression force
Which diagram can be used to describe the deformation behaviour?
the stress-strain-diagram
elastic deformation?
a reversible process, occure at the beinning of the apllied CF.
has a linear relation to the strain
what do elastic material have?
they have a very high young’s modulus yield strength , only in the linear part
what does high young modulus means?
high stress is need for a certin deformation of the elastic material
defination of the young modulus?
it is a measurement used to describe the ability of material to withstand changes in length when under lengthwise tension or compression
plastic deformation?
inrreversible and time- dependent process, permanent change of the particle shape
when do plastic deformation takes place?
when the yied limit is exceeded
hock’s law
it is the linear relation between the stress and strain, can only be applied for elastic and not for plastic material
when does the material starts to flow?
when the yield limit is exceeded, leading to platic deformation
Brittle fragmentation
breaking of the original particles into smaller units
Ductile frature
after plastic deformation has taken place
deformation depends on?
particle size and morphology and the excients properties
what is viscolasticity?
a property of material that exhibits both viscous and elastic characteristics when undergoing defomation
Monitoring of compression process
Force-time-diagram and Force displacement diagram
Force-time-diagram excenter and rotary press (draw it)
do knwo how to draw it?
Whats the main different between the F-T-D in EP and RP?
the plasticity of a mixture can be obtained in the RP by calculating the dwell time coefficient
what is the residual force?
the force which is still applied on the tablet, eventhough the upper punch has left the die
what are the phase in the FTD in a RP?
A1: compression phase
A2 / A3: Dwell phase
A4: Decompression phase
A1 phase?
compression phase, consolidation time.
what affect the area of the A1 phase?
high fluctuation of the CF
tabletting speed
material properites
when is A1 are big?
high CF, low TS and palstic material (more consolidation time)
what affects the CF?
flowability, high tableting speed
A2/ A3 phase?
Dwell phase
dwell time definition?
is the time at which the tablet material is exposed to the maximum pressure, when both head punches are on contact with the material
material begins to flow, resluting to plastic deformation
Dwell phase is affected by?
machine parameter, dwell time.
what is an indication of the dwell time in the FTD
the slightly decrease of force
what affects the plastic deformation?
since it is time-dependen, its affect by high tableting speed–> short dwell time
what is the affect of a short dwell time on the properties of the tablets?
short dwell time, leads to no time for plastic deformation. Therefore, less bonding of the tablet material, high elastic recovering, leading to capping
Decompression phase?
Ejection of the tablets
how does the FTD at higher and slower tableting speed looks like?
the compression force peaks at higher TS are narrower and the time before decompression takes places get shorter
Force-displacemnet diagram, draw of the excenter and rotary press
do you know how to draw it?
explain E1, E2 and E3 in a FDD of a excentre press
E1: mechical engery into the heat energy
E2: elastic to plastic deformation
E3: force is apply to the tablet, but not stored in the tablet
why is the maximum of the up displacement and lp force lower than up displacement and force
due to the friction
draw the FDD for rotary pres for ideal elastic, plastic and combination of both bodies
do you know how to draw it
what is a hysterisis area
the area between the elastic and plastic deformation
the use of the FDD
is used to say something about the properties of the material
Probleme during tableting
tablet weight variation
insufficient tablet hardness
capping and lamination
tablet sticking
tablet weight vaiation?
inconsistent filling
moisture content
stickiness
insufficient tablet hardness
inadequate binding properties
excessive elastic recovering
over lubrication
compression force and speed
capping and lamination
capping: the slpiting of the tablets
lamination: creaking
why do capping and lamination occur
interparticulate bonding
high moisture content
air entrapped
high residual wall pressure
tablet sticking
inadequate lubrication
high adhesive force
high moisture content
what is corrosion?
irreversible damage of material due to chemical or electrochemical reaction
how corrosion be prevented?
routinely washing the surface
sealing any cervices with rubber
passivation
different between MBR and BR?
MBR: exist for each product, whereby BR ia an approved copy of the MBR with filled in data enteries
Name some requirement for the MBR?
name of the prouct, reference product with its sepfication
pharmaceutical form, strength of the products and batch size
statement of the expected final yield with AL
location and the principle equipment
SOP
instruction for IPC
a single continuous document
who gives the MBR?
QA
issuing of MBR
- resonsible to generate a copy for a production
- MBR have to be stamped by QA to ensure the currently valid version
- is issued batch by batch on production orders
- changes made, document have to be review and approval again
- QA have to print out and sign, making sure that the aproved current MBR
BR?
- includes the record sheet of all the prodcution record and support records
- should be kept for a each batch processed
- before processing begins, check for all equipment and workstation
- have be date and sign by the person responsible for the processing operations
