B2. Drying and Pellets Flashcards
Defination of drying
is the removal of fluids, through evaporation, vaporization or subblimation
what is the most used desiccant?
air
what is evaporation?
when drying occurs below the boling point
what is vaporisation?
when drying occures at a temperature close to the boling point and similar vapor pressure
Sublimation
conversion from solid ice to water vapour
how can heat be transfer?
convection, radiation and conduction
defination of convection
density diffrences, moving gas or liquid
radiation
wave motion on material
conduction
molecular contact solid
types of drying method
freeze drying
fluidized bed drying
cabinet or vacuum drying
microwave drying
freeze drying is also know as?
lyophilization
When is FD used?
for thermolabile and hydrolsis sensitive agents (hormones, vitamines and proteins)
the three steps in freezing drying
freezing, primary drying and secondary drying
Learn to draw the FD process
do you know how to do it?
Learn to draw the FD process on the water phase diagram and show were the position of the drying chamber and condenser is
do you know how to do it
why is the freezing phase of a product crucial?
because it determines the morphology and the pore size of the dried product later on
what is the target in FD
it is to solidify all the solutes in crystalline or glass form
describe the initial cooling phase
it is the initial nucleation, when a small fraction of the water crystallizes out , leading to saturation of the solution
which is reaction is crystallisation?
it is an exothermic process
what’s the impact of the exothermic process in crystallization
it leads to an increse of tempertaure, which slightly prevent the solidification
when do we have an increase of the freezing point depression
during the saturation of the solution
what is the results of the increase of the freezing point depression?
Further cooling is required for the solutes and the water to crystallised and completely solidiy
what is the rule of thumb for freezing?
10 K less than the eutectic temperature /tg pf the mixture
what other factor has to be consider beside the freezing temperature
cooling rate
why is the cooling rate important
because it’s influences the nucleation. the faster the cooling rate is the less time there would be for nucleation
What’s the results of less nucleation during the freezing process?
less nulceation would lead to
smaller crystal, smaller pores left behine after sublimation
Primary drying
where most water content is removed
what is important during freezing drying
a constant reduction of the pressure during the all process, to ensure sublimation
How does the reduction of pressure affect the vapor pressure of water?
the vapor pressure reduceses as well, leading to a pressure gradient
What’s the importance of the pressure gradient?
it eases the sublimation of the water crystal. Leaving behind a porous structure
what is the principle of the freezing drying technique?
the vapour pressure of frozen water is significant, which allows the sublimation of water to vapour and it’s removed
how is the pressure gradient maintain?
through continuoulsy removal of the vapour that sublimes
what have to be done inoder to maintain the pressure gradient?
the temperature and the pressure of the condenser should be lower than the drying chamber
when is th end of primary drying step?
when the pressure equalizes on either side of the closed valve marking no further vapour movement
what happend at the secondary drying step
the temp. slwoly raosed allowing the loss of the remaining water by diffusion and desorption
the temperature rise is accompanied with?
a decrease in pressure to facilitete the diffusion of the after vapor
what is spray drying?
is the transformation of fluid feed into dried solid particles by spaying the liquid into gaseouse hot drying medium
three steps of spray drying
atomisation, drying and collection of dried products
what is the process of spray drying
adiabetic process
what is an adiabetic processs?
where th enthalpy of the whole system remains the same at all time
the enthalpy is?
the exchanged between the drying air and the vapour released
meaning of atomisation
it is the dispersion with the size reduction of the feed to be dried
results of atomisation
an increase in the total surface area facilitating prompt evaporation of the liquid
Spray drying: why is the atomisation important?
it could affect the pysicochemical properties and morphology of the product
types of nebuliser
rotary, pneumatic and hydraulic atomizer
rotary atomizer
is in the shape of a disc that revolves, centrigual force atomies the feed
Single fluid nozzle?
the liquid is pumped at higher pressure through a small opening causing the liquid to move in a spiral motion in the swirl chamber
what is the results of the motion in the swirl chamber of the rotary nozzle?
it results in the breaking of the liquid film into tiny droplets as it leaves the nozzle
what is the pneumatic nozzle?
as multi-fluid nozzles that operate by pumping the liquid feed into a stream of compressed gas carrier
what does the resulting friction from the stream of compressed gas carrier caused?
it causes the disintegration of the liquid
spray drying: what happend after atomization?
the liquid then enters the drying chamber where a stream of hot air/ gas dries out the moisture from the particles
what are the direction of the air/gas flow?
co-current, counter current and the combination of both
co-current direction
droplet come in contact with the hottest air
what is ad of the co-current direction?
it results in faster reaching of the locking point for the droplet
what’s the results of the faster drying?
it results to a prompt crust formation
why a crust formation?
Because the remaining moisture is release as the particle falls through the chamber
Spray drying, co current air flow what is the results in a spiral movement
it increase the residence time of the droplets in the chamber till they are completely dry.
counter current
the temp comes in contect with the droplets as it exits the nozzels it lower
what’s the results of the decrease of temp in the counter current air flow?
it results in a delay in the locking point and the shrinkage of the droplets before drying
what is one of the draw backs of the counter flow?
the hottest air hit the driest particle first which increase the thermal load on the particles in the chamber
how are the particles from the co-current
it results in larger particles than thoes from counter current
how does particles in the counter current dried?
it dry slowly meeting the hottest air at the end of the flow
spray dryer: step after drying?
dried particles now are vacuumed to the cyclone separator
what’s the function of the cyclone separator?
it is responsible for the separation of fines
how are the fines separated?
through the sprial air flow in the cyclone the fines centrifuge out with the air flow while the larger particle are weighed down to the bottom for collection
what affects the size of the particles to be seperated?
through the dimensions of the cyclone and the rate of air flow
what are the parameters in spray drying?
outlet temp. , particle size, yield, final humidity product
how does the increase of the inet temp influence the parameter?
it increase the outlet temperature, particle size and yield
final humidity of the product decreases
increase in pumpt rate
increase of the particle size and product final humidty, decrease of the outlet air temperature
increase of the aspirator rate?
increase of the outlet tem, final humity and yield
increase of spray air flow
decresse of the outlet temp, the particle size
why do freezing drying results in faster dissolution?
due to more pores structure, which are formed from the gaps left behind after the sublimation of water crystals
spray drying products?
faster drying due to smaller size, allowing higher surface area for contact with the dissolving
what is the composition of tray dryer?
embedded iron or steel with a high insulted chamber where stainless stell trays are positioned on transferable trolleys.
how does the dry air passed through the material
through a controlled flow way in a circulation form
tray dryer: on what does the effectivness depends?
on circulation and on the supply of regular air
what is important during the tray drying process?
to keep a constant temp and proper airflow throughout the whole process
what will be the effect of a non- proper flow during tray drying?
the deficient flow of air can impacht on uniform drying of the material
why is vacuum applied?
when drying thermally-sensitive products
what does the vacuum does?
so that the evaporated water can get into gas process faster through vacuum pump at a lower temp.
what can be achieve with the FBD?
a homogenous drying of particles
what’s the disad von FBD?
it time and coste intensive, but the temp. can be maintained
why can a better drying process be achieve with FBD
due to compulsory airflow velcoity and temp. a thermodynamic equilibrium is guaranteed
what’s the first step of FBD
the hot air passes through the bed of wet particles with high pressure
2 steps in FBD?
the steam of air comes through the bottom, wich is the fluidized state
how is the vaporized liquid carried out
through drying gases
what’s the ad von the fluidized state?
one has a continuous fluidization , which allows individual solid particles to be freely suspened in the upward flowing air
why does the airspeed increases?
due to the corrresponding to the underlying gravitational forces
what influences most the drying process
the choose of the inlet temp.
what is the effect of a high inlet air?
a crust can be form
how does the moisture evaporates?
from the surface of the granules
how are the evaporated moisture carried out?
through capillaries from the innermost granules of the surface
what does crust formation means?
the innermost part of the particles remain wet
what are the four different method to determine the drying kinetics
periodic sampling/weighting
continuous weighting
intermitten weighting
indirect methods
periodic sampling
during the drying process samples are taken at different times intervals
reused of the samples
continuous weighing
the weight of the sample is continous measured, high noise in the measurement
intermittent weighing
the airstream is cut off when the sample is measured
indirect methods
the air humidity coming out of the chamber can be measured
how can you plot the drying process (learn how to draw them)
the amount of water against time
drying rate against the time
was is the drying rate
the amount of water removed per kg of dry air per time
what is the rate-moisture plot
a combination of the drying curve an dthe drying rate curve
the last plot is?
a temperature-time plot
when can the temp-time plot be obtained?
when the product temp in the drying chamber is plotted gainst time
how is the moisture content measured
using a moisture analyzer
how does the moisture analyzer works?
it uses a thermogravimetric method to determine the mositure content of the sample
what is the process of the moisture analyzer
the sample of an initial weight is insert inside the instrument and by applying heat, the sample will loss by mass by drying
how is the end of the measurement set
set by time or by % of variation weight in certain period of time
what are pellets?
special kind of granules, part of the multiparticulate dosage forms
what’s the size of pharmaceutical pellets?
between 0.2 and 2 mm
use of pellets?
compression process, encapsulated and in clinical studies
what is the main applications of pellets?
for modified or controlled release systems
why pellets for modified release?
due to their spherical shape, good for coating processess
what are the ad von pellets modified relases dosage forms
less dose spread, easily disperse at the GI (leass irritation)
less risk of adverse effects
less plasma fluctuation
Manufacturing process of pellets?
Extrusion-spheronization process
what’s are some drawbacks of the Es process
several complex unit operations
what are the steps in ES?
combination, extrusion, spheronization and drying
combination?
mixing of the powder with liquid in certain L/S
what are the equipment used for the combination process
HSM. planetary and paddle mixers
what’s the aim of the combination steps
to obtained a homogeneous wet mass
what are properties of the wet mass
cohesive plastic mass with self-lubricating peoperties
what should be wet mass not be
non-adhesive
what’s the aim of the Extrusion step?
to increase the density and form cylindrical extrudate
what influences the density and characteristic of the extrudates?
the type of the extrusion
what’s the function of the diameter?
it determine the size of the pellets
which pressure is apply on the extrudates?
it depends on the length of the die
what does the length/radius ratio gives?
the density of the extrudates
what is a good extrudate?
the one with a high density and as well as some cracks
why are cracks beneficial?
to break into regular particles for futher rounding
why should big fractures be avioded?
because they could lead to a big portion of fines
what are the characteristic for futher speronization?
must have mechanical strength to maintain their structure
also brittle to break into uniform lengths equal to their diamter
low friability
induce plasticity
why is plasticity imprtant?
to be converted into sperical pellets
non-adhesion between pelltes, to prevent agglomeration or sticking
spheronisation
broken of the extrudates into small pieces and rounded by two firction forces
what are the two forces during speronisation
particles-particle and particle equipment
what is the aids use in pelletization?
MCC
why is MCC used as aid?
because it is brittle enough for the extrudates that can fragment into small particles an dplastic to deformate into spheres
on what does the breaking and deformation depends?
on the plate type, spheronization time, velocity and the load of the mass
rough plate
more friction, more mechanical energy to be transfer into kinetic energy
low load
i leads into non-spherical pellet, not enough material to particle-particle friction forces acts
high load
the interaction particle-equipment will also be low to achieve disire pellet shape
what is the pelletization process
a convension of the cylindrical extrudates into spherical pellets
drying
the final step of ES process, removal of excesses moisture
the drying of the pellets takes place in?
tray drier of FBD
the characterization parameter of the pettels are?
shape and size of the pellets
why are the two parameters used?
to determined the quality of pellets
Aspect ratio
know the equation
know to draw the aspect ratio
is based on Feret measuremnet which relates the length or maximum feret diamter and the ortho Feret diameter
equivalent diameter
the area of each pellet which relates the pellet size
when are pellets consider as good?
AR below 1.1 and D eq lower than 1400µm
overwetted mass over dry mass
low liquid mass needs higher forces to extrudates, high possibility to fraction into dust due to its dryness
overwetted mass, faciliate th eextrusion
what is the downside of overwetted mass?
cause of uncontrollable agglomerations, especially at high radial velocity
what is another aid to used?
bentonite
what is athe use of the aid?
they are used to retain solvent that is added to the powder
the choice of aid depends on what?
if the system is moisture sensitive and prefer the absend of water
how are the pellets made with MCC
they have low tendency to abrasion and a high yiels strength
spheronization process
smaller rods rounded dumb-bell structures ellipsoid structure sperical particles
why can one not generalized the impact of the frictions plates on the quality of the pellets
because of different parameters such as speed of rotation, moisture content and spheronization time
what’s the essence of the rough plates?
for a shorter spheronization time, a rough plate could form rounder partciles
smooth friction plate?
smooth particle
what are the most important parameter when chossing the friction plate?
spheronization time and the radial velocity
what has to be consider with high feed load?
it could cause agglomeration of the particles
what is granulac?
alphe lactoce monohydrate
which parameter are infleunce by the radial velocity?
AR and Deq, it decreases with high radial velocity
why do the AR and Deq decreases with higher radial velocity?
it results into higher kinetic energy causing particles to get in contact more often, fasten the abrasion process
what is the affect of higher sp. time
longer sp. time would lead to better AR and smaller Deq
is there any significant infleunce of the friction plate on the quality of the pelletes
no differennce in suing the friction plates regarding the aspect ratio
rough plates leads to
higher Deq, bigger partciles size
are the parameter of spe. process indenpend of each other
no
what is the downside of using MCC as aid?
MCC acts as a matrix in which the pellts stays intact even after the API is dissolved
what is the operating principle of the IR moisture analyzer
thermo-gravimetery, Loss in drying
thermo-gravimetry process
to assess the mass loss that occurs when heating up a material
learn to draw the LOD cuve of tray dryer and FBD
do you know
why is the adiabatic process short in tray drying
because of the satuartion of the air, close to the saturation line in the mollier diagram
partciles in tray dryer and FBD are
TD- static, FBD fluidizing
what’s the effect of the several layers during drying in the TD
limitation of diffusion of the air to the deep layers
inhomogeneous and inefficient
what are the process of drying in a FBD?
constant rate period
falling drying
constant rate period
stage where solvent is removed from the saturated surface of the solid particles
which kinetics follows the constant rate period
zero order kinetics
where is the critial moisture content point?
no significant change of the LoD
falling drying
smaller slope, slower drying process
why slower drying during falling drying
drying depends on diffucion
kinetic of the falling drying
first order kinetic
defination of relative humidity?
(partial vapour pressure /saturated vapour pressure )* 100
the amount of moisture the air actually holds and how much it can hold at that temp
dew point
when the moisture in the air cannot be hold back and it depends on the actual amount of moisture in the air
on what does the water qulity depends?
on the bounding capacity of water
high bounding capacity means?
lower is the removal of the water
low bounding effect
free water
example of water with high and low bounding capacity?
high: hydration, adsorbed, hydrate water
low: adhesive, capillary and swelling water
what can be used to determine the water quality?
relative humidity
draw the sorption isotherm diagram and define it
it is the relation between the moisture content of a sample and the water activity
convection
conduction
heat radiation
convection: heat transfer by moving molecules of a gas or a liquid
conduction: takes place in a solid
radiation: heat from a warm body through empty or ga filled space
absorb body in heat radiation
back ( adsorb all hear rays) and white bodyies (reflect)
name example of drying method which are convection and conduction
convection: FBD, Spray and tray dryer
conduction: freez dryer and vaccum drying oven
the mollier H-x diagram is
relationship between the raltive humidity, enthalpy, absolute humdity and temperature
