A1 WG - Experiment Flashcards
Learn about the parameter in a TSG HSG- effect of L/S of torque measurement FBG, granules size
Name equiment with which granulation is possible
Twin screw Granulator
High shear Granulator
Fluid-bed granulator
Name the processes which leads to granules in TSG
Nucleation, layering growth
agglomeration and breakge
Name the elements of a TSG and their functions
Coneveying elements important for transportation
Kneading elements important for compaction and distribution
the feeding system in a TSG
powder feeding and the liquid feeding system
how can you describe the screw?
they are coroating, having temperature jacket for coolin for heating
What is the importance of composition of the screw?
the screws elements determines the process characteristics
what’s the different between the longer and shoter pitch in the conveying element?
longer pitch, faster transportation, material is evenly distributed
shorte pitch length, smaller volume in the length, unevenly distribtion
How does the pitch length affects the granuales porosity?
the porosity of the granules decreases with increase pitch length, due to higher densification
what’s the disadvantges of the shoter pitch?
it leads to oversized granules and fines
What’S the advantage of TSG?
it can be used for continues manufacuring
What are the properites of the wet mass for TSG
The wet mass should be self-lubricanting, fluidity ad rigidit properties and not adhesive
lower angles of the kneading element in TSG
they have a forward flow propeties, more a conveying element
less shear fore, better distribution
higher angles of the kneading element in TSG
reversing kneading, higher pressure and compaction
How does the angle of the kneading element influence the granules properties?
they do not have any significant impact on the PSD of the granules. Nevertheless, increasing kneading elements will produced granules with high density and longer dissolution time
Which parameter were investiged in the A1 experiment?
L/S, feeding rate and srew speed
What is the most siginicant paramter in granulation
L/S ratio, because it affects the mean PSD of the granules.
Low L/S: non-homogeneous weeting of the powder mass. (bimodal granules size distribution
Low L/S affect on the PSD
Low L/S: non-homogeneous wetting of the powder mass. (bimodal granules size distribution
moderate high L/S affect on the PSD
more liquid available for distribution, more wetted and deformation of granules with monomodal size distribution
What’s the affect of the binding viscosity?
too high binder viscosity leads to poor distribution of the liquid, increase of fines
But the viscoity should be high enough to decrease the porosity of the granues, increase stickness
how does the FR and SS affect the granules?
Both impact the barrel fill that can change the shear and compaction forces , theryb influencing the granules size, density and structure
How the MRT affected by the FR and SS
the increasee if the SS leads to descreas of the MRT
why do the MRT reduces by high SS
increasing the SS increase the axial transport rate of the powder, thereby reducing the time the powder spedns in the granulator
Relation between the high MRT and throughput forces?
the decrease of the SS and the FR, leads to an increase of the MRT, due to low throughput force. therefore, the powder stays longer in the barrel
On what does the powder rfeed rate depends?
it depends on the fill level and the throughput force
Why does the increase of the SS and FR doesn’t affect the GS?
due to the no translation of the MRT into the change in the GS, therefore the GS can be maintained at varying screw speed
What is the effect of the low SS on a wet mass?
at low SS, the peak shear rate, axial mixing and the centrifugal force acting on the wet granules are low
Which forces is dominant at a lowe SS to push the granules?
the transport of te granules are mainly through a convective and less disoerive type of transport
What is the affect of the high SS on a wet mass?
the peak shear rate, axial mixing and the centrifugal force acting on the wet granules increase
What is the affect of a high centrifual force
it results in more dispersion transport and a stronger impact of wet granules
what could be the reasons for a small Gs while using MCC
high shearing and friction between the granules-barrel wall and granules-granules
Why does the MRT has an Impact on the GS when using MCC compared to lactos, using water as granulation solution
MCC is insoluable in water less duration for powder-liquid interactions
Why was the peristaltic pump calibrated before using?
Pump speed is shown in rpm, therefore no direct knwoledge about the transport mass which is needed
What does a positive of negative effects means in a main efffect plot?
positive: increase of a factor leads to an increase of the response. For a negative it is just vice visa
What is Flowac 100
it is a spray-dried suspension of fine alpha-lactose monohydrate crstals in a lactose solution. the crstals are bound by amprohous lactose
PVP K30, what does the K stands for?
it represents a functions of the average molecular weight and the degree of polymerization, characterized by it viscosity in aqueous solution
Sieve Anaylsis, in which oder are the sieve set?
in ascending degress of coarseness
How is the mesh of the sieve size defind?
as the number of openings in one square inch of a screen
Out of what are sieve made?
out of woven wire mesh
When is the sieve analysis test complete?
when the mass does not change by more than 5% of the previous mass
Which data must be include in the evaulation?
mass of the test sample, total sieving time and precise sieving methodology
What could impact the sieving process?
humidity, electrostatic properties
the used of Scanning electron Microscopy
it is used for PSD, particle morphology (shape, surface and structure)
how does the SEM functions?
it focused eletrons beams over the surface to create an image.
the eletrons are scatered and absorbed within a teardrop-shaped volumne (interaction volume)
what the results of the SEM process
the eletrons in the beam interact with the sample, producing various signals that can be used to obtain information about the surface topography and composition
How do you caculate the solid mass?
feed rate * t process
How do you caculate the liquid mass?
L/S * m
Pump rate calculation
ml/t pto
pump speed calculation
pump rate + b/m
how do you calculate the fraction in a SA
mass /total mass * 100
Q3 is the..
calculation
cumulative distribution
the first fraction + the scond fraction
q3 is the
calculation
q3 is the probability density distribution
fraction / different in the sieve width
learn the DOE part
have you done so?
how is the process in the HSG called
it is a bottom-up granulation process
composition of the HDG
Mixing bowl with an impeller
copper
function of the impeller
it keeps the granulation material in constant movement
function of the copper?
it is use to beak down larger agglomerates
what is the big ad of the HSG
it is possible to monitor the granule formation, which makes it easier to determine the end point of the granulation process
what does the senor measured
it measures the resistance of the wet flowing material against rotation of the impeller
Why do we measure the torque?
it gives information about the particle size and density of the granules
What are the processes in the granulation?
- Formation of the nucleaus
- consolidation
- agglomeration
- breakages
nuclei phase?
it is the phase where the granulation liquid is constantly distrubted over the granulation material
Why do consolidation happends
Due to the impacts of the impeller and the wall of the machine on the granulation material
What happend during consolidation?
Water is pushed to the outer surface of the granules, leading to densification and so to particles growth
which forces act for further growth of the particles?
cohesive force between the wet surface of the particles
what is the equilibrium in the granulation process?
it is an equilibrium between growth of the particles and the breakages of the agglomerates
When is the end of the granulation process?
at the equilibrium point, no futher growth is possible
What are the 5 different phases of a granulation process
Phase 1 Phase 2 ( funicular) p3: transition p4: capillary p5: suspension
Describe phase 1
adding of the liquid, no measurement of torque due to less resistance of the dry powder against the impeller
describe phase 2 (funicular)
a rapid increase in torque, due to the occurences of agglomeration. Particles are weakly bound to each other
phase 3 (transition state)
No change in the cohesive force between the particles.
the reached of the equilibrium of torque
Phase 4 ( capillary state)
shape increse of torque with increasing liquid volume (filling up of the pores spaces)
Flututation of the torque
Phase 5 (suspension state)
slurry formation, no resistance of the wet mass against the impeller
Learn to draw the diagram of the torque measurement
Do you know how to do it?
what are the parameter that influences torque?
Granules size
liquid amount, deformation property of the granules material and the stickines ability of the wet mass
How is torque defind?
as the measure of the amount of energy needed to rotet the impeller during the granulation process
Stickiness and torque
Stickiness has the highest impact on the increase in torque
Why is stickiness important
it increases the capillary force between the granules and the wall or bewteen granules and another granules
influence of plastic material of torque?
the deformation of platsic material is time dependent, which increases the deformability and the surface properties of the wet granules, leading to increase stickiness–> increase of torque
when happend to granualtion process if a plastic material is used?
the increase of the torque and so reaching the torque equilibrium sate, will require a higher amount of liquid
what’s the ad of using a plastic material?
the equilibrium state stays longer when using plastic material, making it more robust to variation in L/S ratio
which parameter are important to obtained a narrow granule size distribution?
binder selection, its concentration, physical chemical properties of excipeints
process parameters such as impeller speed
PSD granules produced via TSG and HSG
granules from TSG has a narrow PSD than that of HSG
ada of the TSG compared to HSG
TSG, more uniform and efficient distribution at the surface of granules
the two behaviour of the granules growth (learn how to draw them)
Steady growth (easy to control, high deformation system) Induction behaviour (low deformation system
FBG, process
Charging process
fluidization
spraying
drying
Which material can and can’t be be used in FBG
Used:
aeratable material and larger particles with low density
Not used: very small particles, cohesive
Learn how to draw the FBG proces and describe it
inlet air passes the bed with high pressure,
increase air velocity leads to a decrease of the pressure –> increase of the pressure drop
Fuidize motion, where every particle is surrounded by air (faster drying)
What is the boiling fluid bed’?
describe the point, where an increase air velocity doesn’t change the pressure drop.
What are the three ways to apply the nozzle in a fluided-bed?
Top spray fluid
Tangential spray
bottom spray
What are the process variables in TSFB diagram (learn how to draw it)
liquid addition rate inlet air temperature fluidization air volume process air humdity Atomization air pressure
Why is FBG a one-step enclosed operation?
Because serval ingredients can be mixed, granulted, and dried in the same vessel.
what is the ad von FBG- granules?
there are highly dispersible, having porous structure that enhances wettability
for what is the BSFB used?
mainly for coating, because it produces a superior film
Process for the FBG
- Spraying,
- Mositening ( liquid bridge)
- solidification
- finisch agglomerates
what happend after spraying is stopped?
the liquid evaporates, creating solid binder bounds.
what is the property of the agglomerates?
void, as such permitting modified size ad porosity of the agglomerates
Components of the TSFB
air-handling system
product container and expanion chamber
an exhaust system
What is the key parameter in the TSFB
the atomization air volume
what is the effects of the a faster rate of liquid binder addition?
it result in a larger average granules size and less-friable granules
increase in the inlet air temp.
leads to an decrease in average granules size
increase in the atomization air pressure
it leads in a decrease in average granules size because of smaller liquid droplet size
What are the two most significant parameters in TSFB
atomization air pressure and the liquid addition rate
Binder in Wet granulation
gelatin, starch, polyvinylpyrrolidone
On what does the formation of granules depends?
it depends on the type of binder, concentration
how are the granules produced with water as binder solution?
they have loose structure and are friable
What is the main ad von using water as binder solution?
it improves the flowability and disperibility of the powder
what are the three main forces in the TSTB and what are their function?
centriifugal, lifting and gravity force. Thoes forces provide good mixing and results in granules with good content unformity
draw the levels of the FFD have 3 factors
A:-+-+
B: –+–+
C—-++++
