B1. Tableting Flashcards
1
Q
Why do we use the six-sigma process?
A
use to improve the quality of product and so having a productivity and efficiency of the manufacturing process
2
Q
what’s the aim of the SS-process?
A
it is to eliminate defects and reducing variation
3
Q
What’s the DPMO
A
is the 3.4 defects per million opportunities, which is the results of using SS-proces
4
Q
What’s the ad von SS instead of 3 S
A
the UCL and LCL are within the operation window, whereas in 3-S they are not
5
Q
What is the DPMO of 3-sigma?
A
66810
6
Q
Definition of SS
A
a methodology for eliminating variability, defects and waste in a product or process
7
Q
What is the approach in SS
A
a data-driven approach
8
Q
How are defects reduce
A
By six standard deviation between the mean and the nearest specification limits
9
Q
What are the two methodology of the SS- process?
A
DMAIC, DMADV
10
Q
DMAIC?
A
Define (control chart) , Measure ( plots), Analysis (DoE, FMEA), Improve and Control (CC)
11
Q
DMADV
A
Define, Measure, analysis, Design and Validate
12
Q
What is a statistical process control (SPC)
A
it is a tool to translate the variation of a process into values
13
Q
What kind of variation?
A
Special cause and common cause variation
14
Q
Special cause variation?
A
Variation which are larger in magnitude and can be identified
15
Q
Common cause variation?
A
Sum of multitude of effects of a complex interaction
16
Q
control charts are used to
A
use to analyses variation causes
17
Q
What are the three zones in CC?
A
Zone 1: no actions should be taken
Zone 2: Collection of more information
Zone3: Action required
18
Q
Zone 2 and 3 are, and zone 1
A
Zone 2 and 3 are Special causes variation
and zone 1 common cause vairation
19
Q
Of what does a CC consist?
A
Central line (average values) UCL and LCL
20
Q
UCL and LCL are set
A
3-standard deviation, which is only true when the SD is knwon for the giving process
21
Q
What is a start-up phase?
A
where data are collected to create CC
22
Q
Categorization of Data into?
A
Attribute data and continous data
23
Q
Which CC are used in continous data?
A
x-bar, range and s-charts
24
Q
x-bar and R are
A
charts use to defined the stability of the process
25
x-bar and s-chart?
used for checking mean and variation of a process
26
What is the equation for LCL and UCL for x-bar?
LCL: mean - A3 *sd
UCL: mean+ A3 * sd
27
What is the equation for LCL and UCL for s-cart?
LCL: B3 *sd
UCL: B4 * sd
28
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
29
IPC is use for?
Testing of various quality characterist of intermediates and statistical evaluation of results via control chart
30
MSPC?
multivariate statistical PC
| statistical evaluation of process data or by comparison of to histrical data
31
PAT?
Process analytical technology
| Analysis of quality characteristics by PA in real time
32
IPC and guidline?
No information in the guidlines what has to be tested, how and where and how frequently
33
What is the product life cycle?
lap phase, pilot phase
| validation phase
34
lap and pilot phase?
Process design, IPC testing
identify CCP and CMA
Defination of OP limits and inprocess monitoring strategies
--> Data Accumulation
35
Validation phase?
modification of IPC
process qualification
Focus on critical paramater
36
What are process capability index?
measures the ability of a process to produce output within specification limits
37
When is a process capable?
when " almost all" meansurements of a feature produced by the process fall inside the specification limits
38
what are typical process capability indices?
Cp, Cpk and Cpm
39
Cp
process mean (scattering of the process results)
40
limits of Cp?
Cp >1 process meets specification
41
what's the benchmark?
Cp > 1.33
42
When happend if the mean is not centered?
it leads to Cp overestimates process capability
43
Equation for Cp
Cp= UCL-LCL /6 sd
44
Cpk is?
adresses data centering, can be positive, zero or negative
45
What happend if the Cpk is asymmetric?
underestimation of the proces capability
46
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
47
Shewhart chart?
Singel (raw) data points
| not sensitve to small shifts, can easily detect large changes
48
EWMA chart
exponential weighted moving averages of all prior sample means.
49
Cusum chart?
cumulative sum of differences
detects small shifts over time
50
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
51
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
52
Rule of seven?
When 7 points are below or above the limits, assignable cause that needs to be investigated
53
MSpC is important for?
QA but not the sole indicator of product quality
54
lean manufacturing
minimizing waste by getting rid of activites that don't directly generate values for the customer
55
TIM WOODs?
Transport, Inventory, Motion, Waiting, Overproduction, Overprocessing, Defects
56
5S?
sort, set in order, shine, standardize, sustain
57
Poka-Yoke
mistake proofing
elimimation, facilitation, mitigation ( reduce the impact of a failure) and flagging (mak a failure visible)
58
Tablets machines?
eccentric, rotary or a IMA press
59
excentre press
disc is fixed excentre
UP--> densification
LP--> fixed during compression
60
How is the densification on the excentre press?
asymetric, having a sinusidal movement of UP velocity profile
61
the used of excentre press?
use of high CF, production of larger tablets, more in development and partly veternary tablets production
62
Rotary press is use for?
for large scale industrial production
63
Componenen of the RP?
```
serval punches,
stationary hopper,
die table (circular die plate or matric table)
filling by feed feed frame
compression rolls
```
64
what's the feeding sytem in RP
a gravity feeding system with a funnel or force feedig
65
when do we used the force feeder
at higher tableting speed
66
what are the circular motion?
compression rolls, the filling and ejection cam
67
Compression stage in RP?
pre compression, done by small rolls
Main compression densification
68
how is the compaction process in RP?
it is symmetric
69
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
70
How can entrapped air also be remove?
by reducing the tabletting speed
71
How is the densification process in EP and RP?
densification on the EP is one side, leading to different degrees tablet hardness
72
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
73
Compaction:
Application of pressure with Upper and Lower punch--> particle deformation or fragmentation
74
Ejection:
overcoming of frictional and adhesion force, elastic recovery
75
What are the parameter of creating compression force in RP
immersion and fill depth
76
immersion depth
distance between the punchtips at the maximum compaction pressure.
77
the final tablet thickness, porosity and hardness is determine by?
immersion depth
78
how does the ID affects the CF
small ID leads to high CF, higher densification
79
Fill depth?
influences the tablet mass, depends on the position of the LP
80
small fill volume leads to
increase of compression force by a deeper immersion depth
81
when is the force constant ?
For a constant volume at a specified immersion depth
82
press speed?
number of revolution execute within 1h
83
TS affects?
affects die filling and dwell time
84
when can be obtained a constant mass?
when the filling volume is constant
85
what is the relationship between the tablet weight and thickness?
tablet weight is directly proportion to the tablet thickness
86
What is the indication of mass variation?
variation of the CF
87
which 3 parameter are interdependent
tablet weight, thickness and hardness
88
name of forces during compression
UPF, LPF, die wall, stripping, pressure rollers
89
type of Displacement?
UP, LP
| inductive displacement transducers and incremental displacement
90
What are some reversible changes during compaction?
Punch compression, die widening and machine fram streching
91
instrumentation used to control the compression force?
Strain gauge, piezoelectric force transducers and inductive displacement sensor
92
Strain gauge is a?
metallic conductance track glued onto a puch holder
93
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
94
disad of strain gauges?
they are prone to temeperature changes (friction) wherefor correction factors are necessary
95
which law is applied?
OHM law
96
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
97
inductive displacement sensor?
detecting the change in alternating-current reistance which is based in the depth dependent movement of the punch into the die
98
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
99
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
100
which two parameter are proportional to the TM in the strain gauge?
the Cf and voltage for a certain immersion and filling depth
101
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
102
three stages of deformation
elastic, plastic and fragmentation
103
on what does the deformation depends?
on the applied compression force
104
Which diagram can be used to describe the deformation behaviour?
the stress-strain-diagram
105
elastic deformation?
a reversible process, occure at the beinning of the apllied CF.
has a linear relation to the strain
106
what do elastic material have?
they have a very high young's modulus yield strength , only in the linear part
107
what does high young modulus means?
high stress is need for a certin deformation of the elastic material
108
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
109
plastic deformation?
inrreversible and time- dependent process, permanent change of the particle shape
110
when do plastic deformation takes place?
when the yied limit is exceeded
111
hock's law
it is the linear relation between the stress and strain, can only be applied for elastic and not for plastic material
112
when does the material starts to flow?
when the yield limit is exceeded, leading to platic deformation
113
Brittle fragmentation
breaking of the original particles into smaller units
114
Ductile frature
after plastic deformation has taken place
115
deformation depends on?
particle size and morphology and the excients properties
116
what is viscolasticity?
a property of material that exhibits both viscous and elastic characteristics when undergoing defomation
117
Monitoring of compression process
Force-time-diagram and Force displacement diagram
118
Force-time-diagram excenter and rotary press (draw it)
do knwo how to draw it?
119
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
120
what is the residual force?
the force which is still applied on the tablet, eventhough the upper punch has left the die
121
what are the phase in the FTD in a RP?
A1: compression phase
A2 / A3: Dwell phase
A4: Decompression phase
122
A1 phase?
compression phase, consolidation time.
123
what affect the area of the A1 phase?
high fluctuation of the CF
tabletting speed
material properites
124
when is A1 are big?
high CF, low TS and palstic material (more consolidation time)
125
what affects the CF?
flowability, high tableting speed
126
A2/ A3 phase?
Dwell phase
127
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
128
Dwell phase is affected by?
machine parameter, dwell time.
129
what is an indication of the dwell time in the FTD
the slightly decrease of force
130
what affects the plastic deformation?
since it is time-dependen, its affect by high tableting speed--> short dwell time
131
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
132
Decompression phase?
Ejection of the tablets
133
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
134
Force-displacemnet diagram, draw of the excenter and rotary press
do you know how to draw it?
135
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
136
why is the maximum of the up displacement and lp force lower than up displacement and force
due to the friction
137
draw the FDD for rotary pres for ideal elastic, plastic and combination of both bodies
do you know how to draw it
138
what is a hysterisis area
the area between the elastic and plastic deformation
139
the use of the FDD
is used to say something about the properties of the material
140
Probleme during tableting
tablet weight variation
insufficient tablet hardness
capping and lamination
tablet sticking
141
tablet weight vaiation?
inconsistent filling
moisture content
stickiness
142
insufficient tablet hardness
inadequate binding properties
excessive elastic recovering
over lubrication
compression force and speed
143
capping and lamination
capping: the slpiting of the tablets
lamination: creaking
144
why do capping and lamination occur
interparticulate bonding
high moisture content
air entrapped
high residual wall pressure
145
tablet sticking
inadequate lubrication
high adhesive force
high moisture content
146
what is corrosion?
irreversible damage of material due to chemical or electrochemical reaction
147
how corrosion be prevented?
routinely washing the surface
sealing any cervices with rubber
passivation
148
different between MBR and BR?
MBR: exist for each product, whereby BR ia an approved copy of the MBR with filled in data enteries
149
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
150
who gives the MBR?
QA
151
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
152
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
