Pharmaceutical tablets and formation of compressed tablets Flashcards
1
Q
what is the basic set up for a tablet press?
A
- two punches
- one die
- > the die contains a cavity that will be filled with the powder/granule formulation
- > the punches will come into the die during the compression/compaction phase to form the tablet
2
Q
what are the main types of tablet presses?
A
- Single-punch press also called eccentric press
- > low output; 130-200 tablets per minute - Rotary press
- > large scale production; 10,000 tablets per minute - Compaction stimulator
- > optimises compression setting and predicts any issues
3
Q
How does die filling help the tableting process?
A
- die cavity is filled by gravitational flow
- powder properties effect powder flow
- granulation is removed from the direct compression process
4
Q
How can you use glints to improve powder flow?
A
- glints work by decreasing cohesive forces and are added just before compression
5
Q
How can binders be used in the tabletting process?
A
- binders help promote the formation of interparticular bonds
- binders are usually ductile which is important for the compression process
- for tablets prepared by direct compression a binder can be added as a dry powder
6
Q
when are binders most useful? What are some examples?
A
they are most effective when added as solutions during granulation
examples
- starch, sucrose, gelatin
- polyvinylpyrrolidone
- cellulose derivatives: HPMC, methylcellulose
7
Q
How do glidants, lubricants and anti adherents affect compression-compaction?
A
Glidants; help during initial phases of the process- particle rearrangement
Lubricants; added to lower friction between powder and die wall
Antiadherents; added to prevent adhesion of powder/granules to the die wall or punch tips e.g. talc, starch, magnesium stearate
8
Q
how does high MC allow powder stick?
A
it promotes adhesive forces and makes powder stick to the punches
9
Q
How does friction affect tablet ejection? How can any fracture be avoided?
A
- if friction is high tablets may fracture during the ejection process. Lubricants may be added to reduce friction
10
Q
How can lubricants interfere with compression-compaction and dissolution
A
- bonding with compression-compaction; impact of lubricant on tablet strength can be assessed
- dissolution due to their hydrophobicity; use hydrophilic lubricants and added after the disintegrate to avoid generating lubricant-coated disintegrant particles
11
Q
State the mechanisms of action for fluid lubrication
A
- formation of a fluid layer between solid surfaces
- minimise friction between and die wall during ejection
- not used for tablet formation
- can make tablet surface tacky and mottles
12
Q
state the mechanism of action for boundary lubrication
A
- solid surfaces separated by a thin film of the solid lubricant
- tends to be fine particulate solids
- most effective agents (<1%):
- stearic acid
- stearic acid salts; magnesium stearate
13
Q
What are some examples of some glidants?
A
Talc (1-2%)- works as an anti adherent and is hydrophobic; has impact on wetting/dissolution
Starch- helps disintegration and is used as a binder and diluent
Magnesium stearate (<1%)- used as a lubricant and can promote flow at low concentrations
colloidal silicon dioxide- efficient glidant, small spherical particles, can be hydrophilic and hydrophobic; particles “glide” over each other under pressure
14
Q
What are chewable tablets used for?
A
- paediatric patients
- veterinary use; tailored flavouring and safety of excipients confirmed
- adult patients with swallowing difficulties
15
Q
where does disintegration and drug dissolution occur for chewable tablets?
A
disintegration in the mouth but drug dissolution occurs in the GIT
16
Q
what diluents are often used in chewable tablets? What can they act as and what should be considered?
A
sorbitol or mannitol and can also act as a sweetener
- consider organoleptic properties
17
Q
what drugs disintegrate in the oral cavity?
A
- buccal tablets
- sublingual tablets
- compressed lozenges
18
Q
how do buccal and sublingual tablets allow quick disintegration?
A
they are smaller and more porous to enable quick disintegration
- reduced tablet size will also help limit discomfort to the patient
19
Q
how do compressed lozenges work and how are they prepared?
A
- they dissolve slowly in the mouth, and release some of the drug in the saliva
- they are prepared using high compression forces, which increases mechanical strength
20
Q
what specifications must oro-mucosal tablets meet?
A
- they must be of suitable mechanical strength to allow processing and handling without breaking down
21
Q
what are the means of multiple compression tablets? what are the able to?
A
- separate two or more incompatible APIs
- allow the APIs to be released at different rates
- address mixing issues where uniform distribution of the API cannot be guaranteed
22
Q
how are layered tablets formed via tableting process?
A
- a first powder is compacted by compression, before the second or more powder is added to the die and compressed
23
Q
how are tablets-in-tablets prepared?
A
prepared by compression coating. the core tablet is made first and then moved to a slightly larger die containing the second powder
24
Q
what can occur when two powders are layered together?
A
- an interface can be caused and this can lead to stability issues in cases of incompatibility
25
what are the three different configurations that can be formed with tablets?
1. two API-containing layers separated by a drug-free layer to keep APIs separated
2. two API-containing layers with each layer providing different release layers
3. tablet-in-a-tablet
26
how long does it take for ora-dispersible tablets to disintegrate/dissolve?
3 minutes before being swallowed
| break down in the mouth
27
what are the 4 processes in which ODTs can be prepared?
1. moulding
2. spray-drying
3. compression/compaction
4. lyophilisation
28
what excipients are used in the manufacture of ODTs?
- rapidly dissolving fillers are used and sweetening agents will be required
- usually superdisintegrants will be used
29
what tests can be performed for manufacture of ODTs?
1. wetting time test; relating to porosity and hydrophilicity. the shorter wetting time, the faster the disintegration
2. moisture-uptake test; provides info on the stability of the tablets when exposed to humidity
30
what are the disadvantages and advantages of scored tablets?
```
Advantages
- quick drug release
- good patient acceptability
- convenient
- improved bioavailability
Disadvantages
- high hygroscopicity
- low mechanical strength
- stability issues
- taste masking required
```
31
what are scored tablets?
some tablets when manufactured with scores or scoring lines and the scores are used to facilitate tablet splitting
32
what can splitting or breaking a tablet can affect?
it can affect
- uniformity of dosing, unless API is homogeneously distributed through the tablet
- disintegration or dissolution of the drug from the tablet fragments
- stability of the API and excipients become exposed to the environment
33
what is the definition of coating?
coating is the application of an outer layer to the surface of a solid dosage form
34
what are the reasons we coat tablets and other solid dosage forms?
1. to protect the API from light and moisture
2. to mask a bad taste
3. to make large capsules or tablets easier to swallow
4. to control drug release
5. to sustain drug release and where it occurs
6. to allow quick product identification
7. to reduce contamination risk
35
What are the disadvantages and advantages of sugar coating?
```
Advantages
1. low upfront material cost
2. simple
3. taste masking
4. pleasing tablet appearance and tablet is easier to swallow
Disadvantages
1. trained personnel needed
2. multiple steps
3. harder to add tablet marking
4. time consuming
5. intra and inter batch variability
```
36
what can be the other types of coating?
1. film coating
2. spray coating
3. compression coating
37
what are the common issues with sugar coating? what are the solutions for each one?
1. chips in coating; ensure enough polymer is added and check fillers
2. cracks in the coating; apply a sealing coat to prevent moisture-induced tablet expansion and wait longer between compression and coating
3. coating doesn't dry; caused by excess of invert sugar and avoid heating sucrose under low pH conditions
4. surface colour not uniform; ensure enough coating is used and mixing well has occurred. limit risk of colour migration and ensure surface is smooth before applying the coloured coating
5. sweating; caused by excess moisture so optimise the drying steps
6. marbled colour; caused by uneven color surface and so coating should be smooth before waxes are supplied
38
What are the 3 different types of sprays for spray coating?
1. top spray
2. bottom spray
3. tangenital spray
39
describe the sugar coating process
1. sealing of the tablet cores
2. subcoating
3. smoothing
4. colouring
5. polishing
6. printing; identification and branding
40
why are tablets waterproof?
1. prevent stability issues
| 2. prevent water from penetrating the tablet
41
what is the purpose of sealing in sugar coating process?
sealing prevents the core from breaking down during the coating process
42
what is the purpose of sub coating in sugar coating process? what does it require?
- applied to smooth edges and round off the tablets
| - requires bulking agents, binders and anti adherents
43
describe what occurs with smoothing in sugar coating process?
1. application of a sucrose coating
2. completes the tablet roudning
3. facilitates the colouring process
44
describe what occurs with colouring in sugar coating process?
sucrose and colouring agents are applied
45
describe what occurs with polishing in sugar coating process?
provides glossy finish
46
What is the international pharmacopoeia standard for scored tablets?
1. select 30 tablets at random. break each tablet manually and take one part and reject the others
2. weight each of the 30 parts and then calculate the average mass
3. if no individual mass is outside limits of 75 to 120% and and not more than one individual mass is outside the limit of 85-115% of average mass then tablets comply
47
what are tablets?
- solid dosage form and are usually compressed tablets
48
what are some different types of tablets?
- buccal tablets
- sublingual tablets
- compressed lozenges
49
what goes into the tablet?
- one or more API and different excipients
50
what are the main excipients and their roles? give some examples
1. FIller/diluent; bulk up the powder volume e.g. mannitol, lactose, cellulose
2. Disintegrant; aid disintegration and dissolution e.g starch, sodium starch glycolate
3. binderr; formation of granules and tablets with the right mechanical strength e.g for wet granulation PVP, sucrose, starch, HPMC and for dry granulation PVP, cellulose
4. Glidant; improve flow properties e.g. talc 1-2% and colloidal silica 0.2%
5. Lubricant; ensure successful tablet formation and ejection e.g. stearic and magnesium stearate
51
what are three main methods used in manufacture of compressed tablets?
1. direct granulation
2. wet granulation
3. dry granulation
52
what factors can granules impact?
- flow properties
- mixing quality
- compactibility
- dissolution; if particles are hydrophobic/poorly soluble, dissolution is improved by mixing with hydrophobic filler and binder
53
what is low shear wet granulation? any disadvantages
- low speed planetary mixers are used
- wet mass dried in a tay drier
- > manual transfer of material needed
- > long drying times
- > mixing issues due to tray drying
54
what is high shear granulation? any dis/advantages?
high shear mixer granulators are used
+ lower amounts of water used
+ short processing time
+ end-point of granulation can be monitored
+ closed vessel and possible transfer to fluid bed drier
- risk of overgranulation
55
how does fluidised bed granulation work? dis/advantages?
- drug and excipients are loaded into a fluid bed processor and fluidised with air
- granulation fluid is sprayed onto the bed from above with a continuous stream of hot air
+ all steps completed in same equipment
+ easy for the optimised process to be automated
- initial upfront cost
- extensive development work needed for optimisation
56
how can a spray-drier be used for granulation? dis/advantages
dry granules are obtained from a suspension or solution
+ produces fee-flowing, hollow, spherical particles with good compaction properties
- results in material property changes
57
what are some examples of filler/diluent used in wet granulation?
```
microcrystalline cellulose
- diameter of 50 microns
- good compactibility
lactose
- fine grade to ensure sufficient binding
```
58
during wet granulation, how are binders added
2-10% by weight
- added as a dry powder to drug + filler
- added pre-dissolved in water
- need to balance tablet hardness vs. drug release
59
what are intragranular excipients and extra granular excipients?
intragranular- adding of ingredients to the material after granulation within the granule
- filler/diluent
- binder
extragranular- adding of ingredients to the material after granulation outside the granule
- disintegrant
60
how does dry granulation work ands what are its advantages?
the granules are formed under high pressure through slugging and roller compaction
```
+ cost effective
+ versatile method
+ easy to scale- up
+ uniform mechanical strength
+ gentler than slugging
```
61
what are moulded tablets?
prepared by moulding rather than compression in a tablet
+ soft and disintegrates quickly
- small in size, limiting their use to low dose usage
62
how are moulded tablets prepared?
- drug is mixed with a diluent; water-soluble diluents are preferred e.g. lactose, sucrose, mannitol
- > check for incompatibilities of the drug with sugars
- a liquid is added to the powder to wet the powder and allow moulding
- tablet generated after evaporation under vacuum
63
why is dry granulation preferred?
as water can interact with drugs and excipients
| - granules can also be sensitive to moisture
64
what filler should be used for roller compaction?
MCC or anhydrous lactose due to re-compaction properties of product
65
what type of binder should be used for dry granulation?
dry binders
- cross-linked PVP
- pre gelatinised starch
66
what is wet and dry granulation?
wet granulation; high sheer blending/fluidisation with binding liquid; drying and milling
dry granulation; light compression of blend and milling
67
what is the process steps for direct compression?
1. particle size reduction
2. mixing
3. tablet press
68
what is the process for wet granulation?
1. grind the drug
2. blend the drug whilst adding the intra-granular excipients
3. add granulator fluid into the granulator and then wet screen
5. pass through sieve to start reducing the size
6. drying occurs with air inlet and air exhaust; removes the liquid
6. dry screening occurs
7. after granulation process extra-granular excipients are added and blended in with drug
8. compaction occurs to produce tablet
69
what will happen to liquid bridges formed by melted binder
these bridges turn into solid bridges, consolidating the granule formation
70
what are the properties of a hot-melt binder that allow it to be used in melt granulation?
1. hydrophobic wax
2. semi-solid hydrophilic polymer
3. solid hydrophilic polymer
71
what occurs with melt granulation?
hot-melt binder added to drug at room temp and then melted
the binder is then sprayed onto the powder to allow its distribution
then coalescence will occur producing the product
72
what is the movement of punches during the tableting process to produce compressed tablets?
1. upper punch is lifted; lower punch is dropped
2. hopper moves over the die and fills it
3. hopper moves back and upper punch starts coming down
4. upper and lower punches move up
5. tablet is ejected
73
what are the different type of presses used for manufacture of compressed tablets?
1. single-punch press; 200tablets/min
2. rotary press; lower punch moves down to allow die cavity to be filled; at lowest during compression stage so the upper punch will move down
74
what does tablet appearance depend on?
1. shape of the die; oval, circular, oblong
2. distance between punches; tablet thickness depends on this
3. configuration of punch tips
- > flat, convex or bevelled edges
- > score marks
- > markings; debossed= indent on tablets and embossed= raised from tablet
75
what is the process for producing lyophilised tablets?
1. mixing of drug with gelatine and sugars
2. filling of blister
3. freezing
4. freeze-drying and sealing
- produces fast disintegrating tablets
76
in vitro, what can trigger tablet disintegration?
saliva from the mouth
77
what does freezing rate affect?
the ice crystals size and the pores size in tablets
78
why does a tablet need to be porous enough?
so that water can enter quickly and disintegration occur quickly but so that tablet is strong enough not to break easily
79
what type of derivatives can be used for immediate release coating in tablet coating?
cellulose derivatives
vinyl derivatives
aminoalkyl methacrylates
80
what is an example of cellulose derivates for IR coating? what properties make it suitable?
HPMC
- water-soluble
- good film properties
- easy to apply
- +/- colouring agent
81
what is an example of vinyl derivates for IR coating? what properties make it suitable?
- copovidone
- polyvinyl alcohol
- > good film properties
- > PVA = good barrier and protects tablet from tablet and moisture
82
what properties make aminoalkyl methacrylates suitable for IR coating?
- soluble at acidic pH
- taste masking
- for coating; organic solution and aqueous dispersion
83
MR release coating is water insoluble and immediate release coating is water soluble. True or False?
True
| MR solubility depends on pH
84
what type of derivatives can be used for MR coating in tablet coating?
- cellulose derivatives
- methyl methacrylate
- phthalate esters
- methacrylic acid copolymers
85
what is an example of cellulose derivates for MR coating? what properties make it suitable?
ethyl cellulose
- water insoluble
- organic solution
- aqueous dispersion
86
what properties of methyl methacrylate make it suitable for MR coating?
- water insoluble
- permeability
- aqueous dispersions
87
what properties of methacrylic acid copolymers make it suitable for MR coating?
- gastro-resistant coating
- insoluble at low pH
- delivered as aqueous dispersions
88
what properties of phthalate esters make it suitable for MR coating?
- delayed release
| - delivered as an organic solution or aqueous dispersions
89
what defects can occur with tablets due to coating process or due to the formulation?
coating process
- overweening
- overdrying
formulation
- issue with mechanical strength
- > tablet; breakage and erosion
- > coating; cracking, chipping and peeling
90
what additional materials can be used for film coating formulations and why?
```
Plasticizer
- reduce brittleness
- increase film flexibility; triethyl acetate, polyethylene
Colouring agents
- water-soluble dyes; mottling
- water - soluble pigments; opacity, coverage, pigmentation
solvents
- volatile; acetone, methanol
- issues with; environment, safety, cost, traces
surfactants
- spreadability
flavour
sweetener
glossant
```
91
what factors of polymers should be considered for film coating?
- solubility
- viscosity
- permeability
- mechanical properties
92
what goes into a tablet?
API, filler, colour/flavour, disintegrant, binder and a lubricant
93
what do you need to consider for tablet optimisation?
the manufacturing process (technical feasibility) and performance (bioavailability)
94
what properties should a good diluent have?
- inert
- hydrophilic
- non-hygroscopic
- biocompatible
- cost effective
95
what role does a diluent play in tablets?
- bulk up powder volume to ease processing and handling
96
what does it mean by compression and compaction?
```
compression= reduction of bulk volume under applied force; reduction in bulk volume
compaction= formation of a solid with defined geometry and strength
```
97
how can compression be obtained?
re-arrangement- low pressure
OR deformation or densification - moderate pressure
OR fragmentation - use high pressure as it will create new surfaces that may behave differently
98
what phase is the compression phase in tablet manufacture followed by?
compaction phase
| - inter-particular bonds are created that will allow formation of the final tablet will acceptable mechanical strength
99
when manufacturing tablets, what must you be careful not to do? what can this lead to?
you must be careful not to 'over-compress' the tablets and this can lead to the fracture of the tablet through capping or lamination
100
how could you test the compressibility of a material?
1. testing the resulting tablets
| 2. testing compression/decompression events
101
how can the compatibility of a formulation can be measured by
testing the tablet hardness
102
what are the essential properties of a good tablet?
1. be acceptable to patient
2. contain the right drug and right drug content
3. have a pleasing appearance
4. consistent weight, size, appearance
5. release drug in producible and predictable manner
6. good chemical, physical and microbiological stability
7. suitable packaging; maintains tablets integrity
8. strong enough to keep shape during all processes
9. not have any contaminants/excipients that might lead to toxicity
103
why is tablet testing needed?
ensures products quality when finalised
104
if there are problems in the manufacture of tablets what issues can this lead to?
this can lead to issues in
- content uniformity
- uniformity of weight
- appearance changes
105
name the typical tests performed on tablets?
- appearance; checked to avoid cracks, chipped edges and colour
- thickness; useful for packaging
- diameter; useful for packaging
- hardness
- friability
- disintegration/dissolution
- uniformity of content/weight
106
if there is fixed compression forces, tablet thickness will depend on...?
1. die filling
2. tablet weight
3. particle size and distribution
4. packing during compression
107
if the die fill vol. is fixed, tablet thickness will depend on?
compression forces
108
how is thickness measured? what is the max percentage of mean thickness the variation shouldn't exceed?
measured using calipers
| - the variation shouldn't exceed 5% of mean thickness
109
what are the percentage values for diameter in which it can vary?
can vary by:
1. 3% for tablets with a diameter 12.5 mm and above
2. 5% for tablets with a diameter less than 12.5mm
110
what does friability measure?
the tendency to powder, chip or fragment during handling
- placed in a friabilator, dropped and rotated
- mass loss shouldn't exceed 1%
111
what is disintegration?
- disintegration is the break-down of compressed tablets into smaller fragments after admin.
- requires destruction of bonds formed during compaction
- force strong enough needed to overcome inter-particular forces
112
why is disintegration needed for tablets?
- allows drug to be released and absorbed
| - if tablet doesn't break down, only small amount of drug is released
113
how do disintegrants work in allowing tablet breakdown?
- enables water entry
- allows tablet swelling
- releases gaseous materials; acid base reaction allowing co2 release
- > the co2 release means effervescent tablets can disintegrate
114
what are some other methods by which disintegration can occur?
- expansion caused by heating entrapped air; exothermic reaction with h20 causes expansion of air in pores
- disintegrating forces; secondary forces for non-sellable disintegrants
- deformation + recovery; this increases size leads to tablet disintegration due to deformed particles recovering their shape after powder wetting due to h20
- enzymatic degradation; degradation of binder due to enzymes added as excipients or enzymes in body
115
what do enzymes like amylases, proteases and cellulases degrade?
amylases degrade starch
proteases degrade gelatin
cellulases degrade cellulose and cellulose derivatives
116
what are some examples of glidants that can be used and how are they good?
Talc 1-2%; hydrophobic, impact on wetting/dissolution
Colloidal silicon dioxide; efficient, small spherical particles that glide over each other under pressure; can be hydrophilic/phobic
Starch; large quantities needed, helps disintegration, used as a binder/diluent
Magnesium stearate <1%; used as a lubricant and promotes flow at low conc.
117
what can lubricants interfere with?
- bonding during compression-compaction
| - dissolution due to their hydrophobicity
118
Explain what fluid and boundary lubrication is?
Fluid lubrication
- formation of fluid between solid surfaces
- minimises friction between tablet and die wall during ejection
- can makes tablet surfaces tacky
- not used for tablet formation
Boundary lubrication
- solid surfaces separated by thin film of solid lubricant
- find particulate solids
- most effective agents are stearic acid or stearic acid salts
119
what are some examples of diluent/filler?
- lactose, sucrose, glucose
120
why is direct compression or direct compaction good to use in tablet manufacture?
- might achieve faster disintegration and drug dissolution
good for
- relatively soluble drugs with good compatibility for faster drug release
- potent drugs can be mixed with DC excipients
121
what can cause risk of segregation?
wide size distribution/ large particle size
| - working with coarse particles
122
what is the process for compression and compaction of a tablet?
1. rearrangement; re-organisation of powder particles or granules under applied force; low pressure and decreased porosity; has a wide-size distribution so small particles shift through pores
2. deformation; applying pressure- deformation-> densification -> fragmentation-> attrition
3. bonding; formation of interarticular bonds; tablet generated and bulk volume decreases
123
what can the yield point of powders be affected by?
- polymorphism
- salt form
- moisture content
- particle size
- compression rate
124
what occurs with fragmentation?
particle breaks down into smaller size particles
- new surfaces
- small particles can now sift through void spaces
- further stress
125
what is meant by yield stress?
the pressure to move from elastic to plastic
126
elastic deformation is permanent and plastic deformation is only temporary. True or False?
false
when pressure is removed, elastic particles regain shape
plastic deformation is permanent
127
for granules, what can compression lead to?
- changes in the physical properties of the primary powder particles
- changes in physical properties of granules
- depends on primary particles and granules properties
128
for what type of particles is rearrangement limited?
coarse particles
129
for granules what process can occur with the particles?
attrition/erosion; more likely; granules collide with each other or the wall of dye county
fragmentation
elastic or plastic deformation
130
how can compressibility be assessed?
- looking at ejected tablet properties
1. scanning electron microscopy to study fragmentation
2. size and size distribution of degaggregated tablets
- looking at compression/decompression events
1. upper punch vs. lower punch pressure
2. tablet volume/porosity vs. UPP
131
what type of bonding does compression promote?
inter-particular bonding
132
how is bonding most likely to occur for dry powders?
solid bridges
- mixing at the interface between solid
- for tablets it is more likely
adsorption bonding
- result of reduced inter-particular distances
- for tablets made from granules with a binder; binder-binder bonds, binder-substrate bonds, substrate-substrate bonds
mechanical interlocking
- inerparticular locking of irregularly- shaped rough particles
133
how does high compatibility affect tablets?
- a good resistance to fracture
| - a low tendency to cap or laminate
134
what is measured during the hardness test?
compactibility
135
what is capping and laminating?
capping- partial or total fracture of the top/bottom layers In a tablet
lamination- separation of tablet into layers
136
elastic deformation has a negative impact on compactability. True or False?
True
| it causes low tablet strength and higher capping/lamination propensity
137
How does tablet size affect tablet strength?
smaller particles are thought to lead to increased tablet strength
138
how do fragmentation and plastic deformation associate to affect tablet strength?
they associate to increase tablet strength
- fragmentation helps in forming smaller particles and so decreased porosity
- plastic deformation increases area of contact between particles
139
how do binders affect granules compression and compactability?
binders allow granule deformation to occur and bond strength to increase for stronger bonds
140
how is drug content measured?
measured either using uniformity of mass or uniformity of content
it passes for UoM if API content is > or same as 25mg or contributes to > or same as 25% wt
it passes for UoC if < or same as 25mg or contributes to < or same as 25 wt%
141
how to calculate to the uniformity of mass/weight? What are the values of % deviation it should stay in?
1. weigh individually 20 units taken at random and determine the average mass.
2. Not more than 2 of the individual masses deviate from the average mass by more the percentage deviation from BP and non deviates by more than twice that percentage
For 80mg and less= 10%
more than 80 but less than 250mg= 7.5%
250mg or more= 5%
142
for UoC what must the tablet API content comply with to pass the test?
each individual content is between 85% and 115% of the average content.
if individual value is outside this range or outside limits 75% or 125% of the average content it doesn't pass and comply with Test A
if in the 75-125% range then determine individual contents of another 20 random dosage units
143
what is the process of tablet disintegration?
the tablet is wetted -> fluid enters pores -> disintegration; leads to drug dissolution and release and absorption
144
what are the two ways disintegration can occur?
1. wicking
- liquid is absorbed into solid mass by capillary action
2. swelling
- impact of porosity
- fluid absorption leads to disintegrant size increasing
- this breaks down the inter-particular bonds holding the tablet together
145
what does water uptake in process of wetting depend on?
- wettability
- pore size distribution
- disintegrant addition
- compression force
146
what type of disintegrant addition an you add?
intragranular addition ; before granulation
extra granular addition ; after granulation
combo; both before and after
147
how does tablet disintegration occur when in an aqueous media?
it will disintegrate into granules (extra-granular) and then disintegrate into fine particles (intra-granular) and be absorbed into the blood stream
148
out of tablets, granules and fine particles, rank them from fastest to slowest drug dissolution rate
1. tablet- slowest rate of drug dissolution
2, granules- moderate rate
3. fine particles- fastest rate due to increased SA
149
what properties should ideal disintegrants have?
- small particle size for high SA
- gas-liberating
- hygroscopic material
150
what is a superdisintegrant?
- modified starch
- modified cellulose
- effective at low conc.
- good hygroscopicity
- good at swelling
151
what does dissolution determine?
the drug release rate and is linked to in vivo performance
152
how long should conventional and sublingual tablets take in the disintegration test?
- conventional; 5-30 min
| - sublingual tablets; 3 min
153
is dissolution or disintegration the rate-limiting step?
dissolution
154
how can dissolution rates for BCS II drugs be improved
use a polymorph, salt or amorphous form
- particle size reduction
- using a matrix former to increase dissolution rate
- using a dissolution enhancer
155
how does disintegration time change when quantity of disintegrant increases?
disintegration time decreases
156
when a compression force is used how does disintegration time change?
it will decrease and there will be a dip but then it will increase as powder is porous but doesn't trigger dissolution process
157
what factors affect disintegration and dissolution?
- solubility of powder formulation
- type and quantity of disintegrant
- type and quantity of binder
- addition of lubricant; can coat disintegrant decreasing efficacy
- manufacture process selected
158
what factors affecting dissolution must be standardised?
affects drug solubility
- composition, pH and temp of dissolution medium
- agitation speed
- apparatus
- fluid flow inside chamber
- conc. of dissolved substances
- analytical method choice
