Unit processes Flashcards
1
Q
Part 1: size reduction
first step in manufacture of many dosage forms?
A
Particle size reduction
Some powders might form clumps during storage - must be broken-up before the powder can be used.
2
Q
5 aims/ benefits of Particle size reduction?
A
- improve mixing
- increase specific SA: impacts dissolution rate and flow properties
- control texture and feel (organoleptic properties)
- ensure ease of administration, e.g. injectables, mostly for suspensions
- promote stability, e.g. in suspensions
3
Q
define toughness?
A
Toughness is a measure of a material’s resistance to fracture.
4
Q
brittle vs tough material and examples of each?
A
Brittle: fracture/break when subjected to stress. not much energy req. Glass
Tough: requires more energy to break. more difficult to reduce size. Steel
5
Q
difference between plastic and elastic deformation?
examples
A
elastic deformation: change in shape under tensile stress. reversible once stress removed unless if stressed beyond limit
elastic band
plastic deformation:change in shape under stress, permanent once stress removed
clingfilm
6
Q
how do fractures occur in brittle materials?
and in ductile?
A
A brittle material will experience little elastic or plastic deformation before it breaks, fracture will happen through crack propagation; while, a ductile material will undergo significant plastic deformation before it brakes.
7
Q
whats hardness a measure of and what material will be at top/bottom of Mohs scale?
A
measure of material’s ability to resist plastic deformation through indentation or abrasion.
Mohs scale: to compare hardness of diff minerals. Diamonds at top,
talc, a soft material- bottom.
8
Q
why do particle size reduction mechanisms matter?
i.e. what 2 factors influence the process?
A
Both toughness and hardness are likely to influence the particle size reduction process.
9
Q
what phenomenon does particle size red. work through?
A
Crack propagation, i.e. fracture of a brittle material under stress.
10
Q
will deformation from crack propagation -> particle size red. be permanent or temporary? why?
A
deformation = permanent as the stress ->bond rupture.
The crack is propagated along the flaws in the material and happens at high speed in the solid.
11
Q
what affects the efficacy of the particle size reduction process?
A
the ability of the material to resist crack propagation or brittle fracture will affect the efficacy of the particle size reduction process.
12
Q
only little energy provided to system is used to reduce particle size. not very efficient!!
how is most energy lost?
A
most of the energy is lost through
heat, friction, vibration, crack initiation or elastic/plastic deformation.
13
Q
how does PSR of harder materials compare with very soft?
A
both can be difficult!
hard = wear and tear to equipment
very soft e.g. rubber- also problematic
14
Q
what is beneficial about rubber and other waxy/sticky materials that allows PSR to be performed (at low temps)?
A
become brittle when cooled at low temps (often well below freezing point)
15
Q
reason for PSR (linked to behaviour of powder)?
A
PSR = narrow size distribution = impacts behaviour
16
Q
how does particle size affect PSR process?
2 responses to milling
A
will respond diff
bigger: change size
can be
- bimodal: alr reduction in size
- unimodal (normal distribution)
17
Q
after time, what ahppens to the normal distribution unimodal curve in milling/PSR process?
% freq/ diameter graph
A
peak moves to left (i.e. smaller diameter)
overall particle size reduced :)
18
Q
in PSR process, why do we not want to reduce size too much?
A
cohesive (like) forces increase
implications on powder flow
19
Q
4 Different types of mechanical stress that can be used to break down particles. (PSR methods)
A
cutting
compression
impact
attrition
20
Q
PSR reduction methods
what is compression? how is it done in lab
A
Pressure applied to break down the powder.
In the lab- mortar and pestle
21
Q
PSR reduction methods
how is impact done?
A
powder hit by hammers or porcelain/stainless steel balls
22
Q
PSR reduction methods
whats attrition?
A
Fragments breaking away from a larger powder particle under shear, friction, agitation, etc.
23
Q
what are each of the 5 mills in PSR used for?
cutting mill roller mill hammer mill ball mill fluid energy mill
A
cutting mill: cutting
roller mill: compression
hammer mill: impact
ball mill: impact and attrition
fluid energy mill:impact and attrition
24
Q
particle size range that can be used in each of the 5 mills of PSR? i.e. put in order smallest-biggest
cutting mill roller mill hammer mill ball mill fluid energy mill
A
ball mill
hammer mill
cutting mill
roller mill
fluid energy mill (anything up to 50,000 microns)
25
whats the principle of cutting mill?
Particles fractured between 2 sets of knives.
| A stationary set on the mill casing and a set attached to the rotor.
26
whats the principle of roller mill?
Powder is compressed between two rotating cylinders.
27
whats the principle of hammer mill?
Particle size is reduced upon impact driven by 4 (or more) rotating hammers
28
whats the principle of ball mill?
rotating cylinder filled to 30-50% with balls. The mill can be filled with a variety of ball sizes to improve the size reduction process.
29
whats the principle of fluid energy mill?
Air is injected at a high-pressure, creating turbulence = particle collision with other particles and with the wall of the mill.
30
what does Particle size reduction: method selection depend on?
intended use of the powder
Beyond this, method selection will depend on particle properties (i.e. toughness and hardness).
31
!!
what PSR method used to produce VERY coarse powders (> 1000 microns)
Cutting methods for tough/soft particles
| Roller or hammer mill for harder particles
32
!!
what PSR method used to produce coarse powders (50-1000 microns)
Soft/tough materials: size reduction performed under liquid nitrogen
Cutting still possible for soft materials, under liquid nitrogen
33
!!
what PSR method used to produce fine powders (<50 microns)
Ball or vibration mill
| under liquid nitrogen for soft materials
34
how can Size separation be performed? 3 methods
Size separation can be performed using:
1. sieving methods
2. sedimentation
3. elutration
35
size separation:
| 1. sieving methods can be used with or without help of?
w/w out agitation, brushing, centirfugation
36
what is 2. sedimentation based on?
similar principle as sedimentation-based particle size analysis
37
what is 3. Elutration?
separation under a fluid layer moving upwards
38
What is the difference between a brittle and plastic material?
Plastic materials change shape permanently
Brittle materials undergo limited elastic or plastic deformation before breaking
39
benefits of PSR?
Increased Dissolution Rate.
Improved Drug Delivery.
Increase therapeutic effectiveness of certain drugs Pharmaceutical suspensions require finer particle size. Reduces rate of sedimentation.
40
How does particle size reduction affect size distribution?
| what should be seen at end of PSR process and during initial?
should see a decrease in the size distribution.
| In the initial stages, distribution might be widened.
41
factors to take into consideration when choosing a particle reduction method
intended use,
target particle size
or powder properties (e.g. hardness/toughness)
42
TRUE or FALSE: A cutter mill can be used to produce fine particles from a hard material
FALSE: cutting mill is used to produce coarse and very coarse powders.
43
Part 2: mixing
3 ingredients mixing can involve?
Solids
e.g. tablets, capsules, sachets, bulk powders
Liquids
e.g. emulsion
Solids in liquids or semi-solids
e.g. pastes, suspensions
44
Mechanisms of mixing
STATE the different types of mixing/mixtures (3)
Positive (simplest)
Neutral
Negative
45
Describe the main mechanisms leading to mixing (2)
Small scale mixing: using simple equipment
- mortar and pestle
- glass tile
- closed container
Large scale mixing: Industrial-scale
Convection
Shear
Diffusion
46
Explain what demixing is and how it can be prevented
separation of individual powders from a powder blend = huge implications for quality and uniformity of solid dosage form
Powder blends are neutral mixtures: so easiest way to avoid demixing = limit handling of the powder bed.
47
why is PSR often a pre-requisite to mixing?
helps incorporation and more efficient mixixng, successful outcome quicker
48
what = ideal mix (of both powders evenly distributed in powder blend)?
true if both powders:
- similar quantities
- similar powder properties
49
whether mixing and demixing is spontaneous or not has an influence on what?
The type of mixing:
| positive (simplest), neutral or negative mixture
50
What mixture category do powder blends fall into and what does this mean?
neutral mixture category
mixing and demixing = NOT spontaneous
- energy input required for powders to mix/ demix
51
describe the type of mix most likely to result form mixing 2 powders
random mix (not ideal mix)
not completely uniform.
zones with higher conc of Powder A/B.
52
a caution when taking small samples of random mix of 2 powders etc.?
can work with this but ensure good distribution of both powders when you take small samples
53
technique used for small scale mixing (when unequal amounts of powders are mixed together)?
use mortar and pestle
Doubling-up technique can also help achieve a good distribution when unequal amounts of powders are mixed together.
54
Describe the different types of mixing/mixtures (3)
- is mixing spontaneous or not?
- is energy needed?
Positive (simplest)
- spontaneous mixing
- energy only req if time constraint
Neutral
- non-spontaneous mixing and demixing
- need energy input
Negative
- spontaneous demixing: fast/slow
- need energy input
55
which type of mixing is least problematic in drug formulation?
positive.
leats likely to demix
also spontaneous mixing- can occur between miscible liquids, gases e.g. air
56
when is segregation/demixing of powders likely in a neutral mixture?
only if its disturbed
57
why is negative mixing a challenge in drug formulation?
spontaneously demix- can happen fast or slow
58
example of negative mixing?
emulsions w no stabiliser- must input energy to mix oil and water
once mixture left to rest, O and W will spontaneously demix
59
3 steps/ mechanisms of large scale industrial mixing?
1. convection
2. shear
3. diffusion
60
large scale: what is 1. convection mixing?
| what is it the main mixing mechanism for?
powder moved in bulk from one part of powder to another.
Convection = main mixing mechanism for agitator mixers
61
2 types of convection mixers and what do they acheive?
planetary mixers and ribbon mixers
achieve macromixing (i.e. mixing of large groups of particles), which is large scale mixing under stirring.
62
convection mixers: 2 pros, 1 con?
+ can mix powders with poor flow properties
+ lower risk of segregation/demixing vs tumble mixers
- dead spots (where no mixing) in hard to reach corners. hard to avoid
63
large scale: what is 2. shear mixing?
| 2 types?
layers of bulk powder are moved during the mixing process.
| v blender and High-shear mixer granulator
64
what mixing is acheived in shear mixing (large scale)?
what is this process the main mechanism for?
semi-micromixing, intermediate between the macromixing of agitators and micromixing (i.e. mixing of individual particles) of diffusion methods.
Shear mixing is the main mechanism for:
Tumbling agitators
65
large scale: what is 3. diffusion mixing and type?
individual particles are moved during the mixing process.
| This allows micromixing as particles rearrange as they mix.
66
Diffusion mixing is the main mechanism for?
| and whats the method typically used for?
Fluidised bed mixers
Typically used to dry and coat granules, but can allow for mixing of powders before granulation
67
3. diffusion mixing: 2 pros 1 con?
(+) Allows mixing and granulation in the same bowl
(+) True random mix
(-) Low mixing rate
68
State the different types of demixing: 3 methods
Percolation
Trajectory Segregation
Dusting out
69
3 possible causes of demixing?
(lack of uniformity)
Demixing is more likely in powders with a wide distribution of
- sizes
- densities
- shapes
- surface properties
70
density of powders is a more considerable factor in what pharmaceutical prep, which may then induce demixing?
fluidised beds
71
how do different shapes (wide distribution) of powders cause demixing?
spherical = better flow = better mixing BUT also higher risk of demixing
irregular = more cohesive = lower risk of demixing
72
what may lead to a non-homogenous distribution of the different components within powder bed.
and what powders may demixing be more likely in?
Powder particles with similar properties will accumulate in different zones within the powder bed, leading to a non-homogenous distribution of the different components.
Demixing may also be more likely in powder with good flow properties!!!!
73
demixing: when may shape of powder particles vary? and affect demixing?
shape may vary as the powder is process/handled, for example through attrition
74
what type of demixing is PERCOLATION and when does it occur?
size based separation
happens when powder moved about:
- vibration
- shaking
- pouring
75
examples of situations when percolation may occur?
brazil nut effect: shake and larger nuts float to top as smaller ones occupy the tight spaces at bottom.
same with cereal: shavings fall to bottom
76
what type of demixing is TRAJECTORY SEGREGATION and when does it occur?
size based separation
difference in kinetic energy
77
how does trajectory segregation demixing occur? mechanism
larger larticles farther than smaller before settling.
happens on conveyer belts
(pile of powder)
78
what particles can trajectory segregation occur for?
difference in kinetic energy of larger vs. small particles or for particles of similar sizes but different densities
smaller particles around periphery of powder heap
79
how does demixing method DUSTING OUT occur?
small particles are lifted and settle at the top of the powder bed
done by air flow
80
what is dusting out method also called? (2)
fluidisation segregation
| elutriation segregation
81
what is being referred to in the following terms of particle density:
a) particular density (m/Vp)
b) granular (m/Vg)
c) bulk (m/Vb)
a) vol occupied by 1 particle
b) similar to a, aggregates of individual powder particles
c) vol occupied by powder bulk
82
when is particular and granular density equal?
if particles are not porous
83
how are the following measured?
a) Vp (particular density
b) Vg (granular density)
c) Vb (bulk density)
a) displacement of helium
b) " of mercury
b) in a measuring cyclinder- inc void spaces
84
how is DENSITY BASED SEPARATION done?
downward movement of dense particles
gravity = main issue
impact on:
- trajec segregation
- percolation (denser + smaller)
85
how is SHAPE BASED SEPARATION done?
sphere: better flow, higher risk of demixing
irregular: more cohesive, lower risk of demixing
86
what are the 5 mechanisms of demixing?
size:
- percolation (cereal)
- traject segregation (heap)
- dusting out (air flow)
density:
- downward movement of dense parts)
shape:
- spherical vs non
87
Suggest methods to prevent/ lower the risk of demixing (4)
size based separation (particle shape/size reduction
density based separation: avoid large differences
shape based sep: processing
general:
- granulation: even distrib
- reduce vibration/movement/ disruptions
- reduce processing
88
whats ordered mixing?
adhesion (diff) of small particles (<5microM) on large carrier particle
89
why is ordered mixing done i.e. benefits?
imporve powder flow: small parts are cohesive: negative impact on flowability.
adding them onto carrier particles = larger size better flow :)
90
problem with ordered mixing?
demixing still possible!
- large size distrib of carrier particle
- displacement segregation- binding sites ot CP competition
- not enough CPs for all small ones. few small left :(
91
testing mixing efficacy: how is it done? (formula)
mixing index = (content stdec random mix) / (content stdev sample)
92
testing the mixing efficacy formula for mixing index is reliable if what? (2)
sufficient num of samples tested (min 10 from powder bed)
| suitable analytical technique (Near infrared!)
93
when is near infrared analysis used in pharm?
to test mixing efficacy (index)
most pharms absorb in NIR region 800-2500nm
94
Are powder blends positive, negative or neutral mixtures..
| and What does this means for their ability to mix and demix?
NEUTRAL mixtures
| Powder blends will not mix or demix spontaneously.
95
Explain the difference between convection, shear and diffusion mixing
Convection: the powder is moved in bulk from one part of the powder to another
Shear: layers of bulk powder are moved during the mixing process
Diffusion: individual particles are moved during the mixing process
96
What is percolation?
Why does it occur?
How can differences in density make it worse?
What? accumulation of small particles at the bottom of a powder bed
Why? increased risk if the powder is disturbed
Density? can be potentiated if the small particles also have a higher density
97
ow can granulation prevent demixing?
by reducing size distribution and uniformising particle density
98
Section 3: Granulation
Explain how granulation affects powder properties
Explain how granules are formed
What are the 3/4 main granulation bonding processes/mechanisms?
adhesion and cohesion
liquid bridges
Solid bridges and other attractive forces
99
when do adhesion and cohesion forces occur and how do they form granules?
forces occur when have small amount of liquid
thin liquid layer= enough to bring parts together and increase conpact pores, stick to powder parts, sticky, aggregation of granules
100
when is absorbed small amout of moisture (from increased contact area) useful in granule formation? i.e. what process
adhesion and cohesion
normally - effect on powder flow = stickier.
but flow of powder prevented with adhesion and cohesion. part of process for granulation!
101
role of viscous adhesive solution in granulation? (increased contact area)
intervening to exploit adhesion and cohesion= form stronger granules: relatively stronger bond e.g. starch mucilage as gran fluid
102
what are liquid bridges? (granulation: bonding mechanism 2)
interfacial forces in mobile liquid films
103
(liquid bridges) whats wet granulation and hows it done?
given vol of gran lfuid mixed into powder.
| done using diff mixers e.g. planetary
104
5 states/stages of liquid bonding to form granules?
dry state: individual powders, no strong bonds, some moisture
pendular: GF forms some bonds, some void spaces (decrease as more GF added)
funicular
capillary: GF and surface tension create strong bonds
suspension
105
whats happened in final stage of liquid bridges- suspension?
| and why is it not desired?
GF and solute parts suspended in drug.
most drugs DONT WANT THIS! too much GF.
dry to move back to state 4: capillary
106
why is liquid bonding stages of granulation reversible?
liquids! dry to go back stages/ add GF to go forward
107
whys liquid bridges an important process i.e. what does it create between parts?
create more permanent bonds between and strengthens bonds
ideal: want dmthn stronger and permanent at end so wont fluctuate too much
108
what else in liquid bridges mechanism will also help to move through the different stages, for example, from funicular to capillary stage.
agitation
109
Granulation mechanism 3: solid bridges- what do they replace?
liquid bridge formed during gran process
turn into something more permanent
110
how are solid bridges formed? after liquid bridges
| 3 possible mechanisms
during drying after wet granulation.
drying through:
- crystallisation of solutes
- hardening binders!!
- partial melting
111
how is crystallisation of solutes done? (to form solid bridges in granulation mechanism 3)
dissolution in GF
then that dissolved solid will recrystallise upon drying (form solid bridges between parts)
e.g. lactose when water used as GF
112
what does crystal size of solutes in gran mechanism depend on?
crystal size depends on drying size
longer = bigger crystals
113
relying on crystallisation of API, consequences?
size are important, impact on dissolution rate!
114
how is hardening binders process done? (to form solid bridges in granulation mechanism 3)
binders used in wet gran.
harden/crystallise during drying
adhesive soluble in GF
granules dry, this recystallises and form bonds
115
3 examples of hardening binders used in wet gran?
polyvinylpyrrolidone
cellulose derivatives
pregelatinised starch
116
how does crystallisation of solutes, and use of hardening binders differ in process of forming solid bridges?
with HB: not relying on dissolution of random solute,
| adding excipient to form so it contributes to formation of solid bridges
117
common mechanism for solid bridge formation during wet gran? out of 3 options
hardening binders
118
how is partial melting done? (to form solid bridges in granulation mechanism 3)
melting of solid under pressure
- dry gran! pressure to powder, particles closer, form aggregates
- binding upon recrystallisation
not usually most important mechanism
118
how is partial melting done? (to form solid bridges in granulation mechanism 3)
melting of solid under pressure
- dry gran! pressure to powder, particles closer, form aggregates
- binding upon recrystallisation
not usually most important mechanism
119
what forces used for granulation when no solid/liquid bridges can form?
other attractive forces:
electrostatic: rel weak
van der Waals: stronger.
- granule strength during dry gran.
- stronger at short interparticular distances
120
granule formation
3 steps?
nucleation: powder particles come together, liquid bridge bonding (adhesiom)
transition: nuceli growth. pendular bridges, nuc aggregation, wide size distr
ball growth: into granules
121
why is final step in granule formation (ball growth) not really wanted?
as issues associated with excessive growth.
tabs/caps usually stop at stage 2: transition
122
what 2 states of granules usually in step 1 of gran fomration (nucleation)?
pendular
| capillary
123
4 possible mechanisms of ball growth to form granules (final step out of 3)?
coalescence: 2 granules fuse-> bigger
breakage: stong and weak grans. weak break and absorb others
abrasion transfer: friction between, some absorb on surface
layering: spheronisation (controlled release grans) add 2nd powder, absorb on surface of parts
124
possible issue? with the 4 mechanisms of ball growth and why is it therefore desired to stop at transition step?
excessive growth, i.e. all 4 mechanisms may overlap and happen at same time, hard to identify which responsible.
coalescence:
breakage:
abrasion transfer:
layering: spheronisation
125
What are granules? How do they differ from dry powder particles? (2)
Granules are aggregates of powder particles. Granules will have a larger size and a different particle density (granular density)
126
How does granulation affect/ improve powder flow?
Biggest impact will likely be through an increase in size
127
How does granulate affect particle size and size distribution?
Increase in size and (hopefully) decrease in size distribution
128
TRUE or FALSE: Stopping granule formation at the transition stage is adequate for granules used in capsule or tablet manufacture.
TRUE
129
TRUE or FALSE: Demixing is impossible if granules are used. Justify your answer
FALSE. Demixing can still happen, depending on the quality of the granules.
130
last unit process: drying
Explain the difference between bound and unbound water
unbound = easily remoevd by drying (FREE moisture content)
bound = not removed easily, use specific methods after drying
unbound (EQM moisture content)
- gelatin capsules etc.
131
moisture content is the sum of what 2 types of MC?
moisture content
-> total moisture content
1-> free moisture content- unbound water - drying
2-> equilibrium moisture content - bound water- hydrates
132
how is bound water present in a formulation? (2) and a key word
absorbed on surface of solid/
| integrated within chem structure (mono hydrate)
133
Explain how relative humidity can affect drying
at high % rel hum: MC decreases because unbound/free water lost easily
then, % rel hum decrease: eqm water harder to remove and slower curve
134
what are dessicators and give examples?
protect from humidity e.g. silica gel beads in bag/shoes
absorb humidity form air and shift curve of EQM MC
135
why is it hard to maintain a very low MC (drying curve)?
| i.e. why does MC increase in atmosphere?
because EQM water will change w rel hum, goes back up
moisture good but too little = problem (static charge: prevents flow)
136
What makes drying efficient? (4)
A large contact SA
Efficient heat transfer
Efficient mass transfer
Efficient vapour removal
= same factors that will mean clothes or a mopped floor will dry faster!
137
considerations for drying method selection? (7)
```
Properties of the powder
Sensitivity to heat
Physical properties
Nature of the liquid to be removed
Amount of powder to dry
Need for sterility
Available source of heat
```
138
name the 5 main drying mechanisms?
Convection: bulk movement of heated air (e.g. convection oven at home)
Conduction: heating by contact with a hot surface (e.g. fan oven)
Radiation: heat transfer by radiation (e.g. microwave oven)
Spray drying: drying of liquid into a solid particle
Freeze-drying: drying through sublimation
139
Convection drying: Advantages? (7)
- bulk movement of heated air (e.g. convection oven at home)
```
High drying rates
Shorter heat exposure
Constant rate
Uniform
Attrition
Free flowing particles
Decreased risk
- Migration
- Aggregation
```
140
Convection drying: Disadvantages? (5)
- bulk movement of heated air (e.g. convection oven at home)
```
Dust production
Segregation
Small particles trapped on filters
Static electricity
Risk of explosion!
```
141
example of 1. convection drying
fluidised bed dryer (as seen before)
142
Describe conduction drying? and give example
- heating by contact with a hot surface (e.g. fan oven)
Wet solid in contact with hot surface
e. g Vacuum oven/ tray drying
- Drying at lower temperatures
- Reduction in pressure reduces temperature required water can be removed at 25-35 °C
143
Radiation drying 5 advantages?
- heat transfer by radiation (e.g. microwave oven)
Rapid drying at low temperatures
High thermal efficiency
No dust/attrition
Reduced solute migration
144
Radiation drying 2 disadvantages?
- heat transfer by radiation (e.g. microwave oven)
For smaller batch sizes
| Hazardous radiation
145
what is spray drying and give 2 example applications
drying of liquid into a solid particleDrying of individual liquid droplets to generate individual solid particle
- Atomizer
- Drying chamber
Applications:
- Thermolabile compounds
- Dry powder inhalers
146
Spray drying 3 ads
Efficient heat/mass transfer
Rapid evaporation
Improved flow
147
spray drying 2 disads?
Cost (money and space)
| Low thermal efficiency
148
Freeze-drying (lyophilisation) process used for?
drying through sublimation
```
Heat-sensitive materials
Sublimation
- Solid to gas
Light and porous solid produced
- Quick dissolution
- Hygroscopic!
Powders for injection
```
149
Suggest an appropriate method to dry a wet powder/ wet solid in contact with hot surface
conduction drying (vaccuum oven)
150
Explain what solute migration is
solution moving towards surface
| and taking any solid dissolved within it
151
consequences solute migration can have
then give two other things which may happen
surface becomes populated by the solid
changes solute conc: uniformity issues
loss of drug on granule surface
also
- mottling in coloured tabs (intragran mig of colour)
- migration of solute binder
152
drying issues: describe the 2 types of solute migration
intergranular
- gran-gran, short intergran distances (Tray drying)
intragranular
- movement wihtin a single gran
- solute moving to gran surface
153
how is mottling in coloured tabs (drying issue consequence) fixed? (3)
fix high colour density on surface by:
decrease gran size
change GF
adsorbption on alumina particles
154
what does migration of soluble binder mean for the strength and bonding of granules?
(drying issues consequences)
layer of binder on gran surface
= harder grans
, may help bonding during compaction
155
how to prevent solute migration? 6 ways
- Add an absorbent powder
- Control solubility: limit affinity for the fluid
- Use viscous granulation fluids
- Select the drying method carefully
- Limit the initial moisture content
- Control the granule size
156
2 examples of absorbent powders to add to prevent solute migration and role?
Starch, microcrystalline cellulose
will increase affinity of solute for granule, rather than GF.
157
why use viscous granulation fluids to prevent solute migration?
method 3
diffusion rate reduced in viscous liquids
158
how to select drying method carefully to prevent solute migration?
ensure that heat is distributed uniformly
- lower risk with microwave vs tray drying on static surface
keeping the particle moving might help
- intragranular migration still an issue
159
how does moisture content affect/induce solute migration?
the higher the initial moisture content, the more likely issues will be
160
why will Controlling the granule size prevent solute migration?
the larger the granules = more likely drying issues
| use the smallest size that will not impede flow
161
What can happen if granules are overdried (i.e. moisture content is too low)?
Granules can break down to individual powder particles.
162
What are the main differences between bound and unbound water?
Differences include the fact that unbound water is easily removed by drying using common techniques. Bound water is equilibrium moisture content and can change with the % relative humidity.
163
Name one advantage and two disadvantages of water as a granulation fluid.
See feedback to LabPrac 2-3 as this was one of the questions!
You need to think also about the temperature/time needed to remove water and what this could mean for solute migration and chemical stability
164
What is sublimation and how can it be applied for drying?
Sublimation is the transition from solid to gas. For example, from ice to vapour. Sublimation is exploited in freeze-drying.
165
Name an application of spray-drying, other than as a drying method
At the time this question was set in week 5, mixing was the most likely answer. However, you should now be able to suggest other applications, including for coating and granulation
