D7 Disintegrants and tablet disintegration Flashcards
(102 cards)
1
Q
what do disintegrants do?
A
- aid disintegration and deaggregation process of tablets
- disintegrants normally cause rapid disintegration of the tablet upon exposure to moisture (conventional tablets)
2
Q
what environments do disintegrants work in?
A
- has no purpose in a dry environment but starts working in a wet environment
- starts disintegrating tablet into fine particles
3
Q
what 2 mechanisms can disintegrants be divided into?
A
- gelatin
- wicking excipients
4
Q
describe the gelatin division of disintegrants mechanism of action
A
- sits as a dry powder without water present
- takes water and starts swelling and pushes particles around and makes tablet disintegrate
5
Q
describe the wicking excipients of disintegrants mechanism of action
A
- wicking materials sit in tablets as long particles not doing anything when its dry
- when water is available they pull lots of water into the tablet along their length
- macromolecule has an extremely high affinity for water and take all the water to the inside of the tablet so it falls apart
6
Q
what state must a drug be in to be absorbed through GI epithelium?
A
drug must be dissolved in GI lumen
7
Q
how can the rate of drug absorption be determined in relation to disintegration / dissolution?
A
can be determined by the rate of drug dissolution from tablet
8
Q
which drugs may require rapid dissolution?
A
those that need to be absorbed in upper part of GIT
9
Q
state the 6 steps of disintegrants mechanism of action in order
A
- wicking
- swelling, strain recovery, dissolution
- interruption of particle-particle bonds
- disintegration
10
Q
explain the wicking process of a disintegrant’s mechanism of action
A
- water imbibition into the powder compact
- improve penetration of water / aqueous medium into tablet (microcrystalline cellulose)
- results in disintegration, by rupturing the intra-particle cohesive forces that hold the tablet together
11
Q
describe the swelling stage of a disintegrant’s mechanism of action
A
particles enlarge omni-directionally
12
Q
describe the strain recovery stage of a disintegrant’s mechanism of action
A
particles enlarge uni-directionally
13
Q
describe the dissolution stage of a disintegrant’s mechanism of action
A
dissolves excipients from the pore walls
14
Q
describe the action of disintegrants regarding how they increase water penetration
A
- primarily swells hydrate and change volume
- the channels for penetration are widened by physical rupture and the penetration rate of water into the tablet increased
15
Q
what are the most commonly used conventional disintegrants currently?
A
starch
microcrystalline cellulose
16
Q
describe starch as a conventional disintegrant
A
- the most common
- cheap
- granular
- native (starch-maize, potato) or pre-gelled starch
- 2-20% used
17
Q
describe the mechanism of starch as a disintegrant
A
predominantly deformation and swelling
18
Q
what is microcrystalline cellulose more familiar as? (rather than a conventional disintegrant)
A
- more familiar as a compression aid
- but also aids disintegration
19
Q
how does microcrystalline cellulose aid disintegration?
A
by having good water transport properties
20
Q
what is the mechanism of microcrystalline cellulose as a disintegrant?
A
predominantly wicking
21
Q
state 3 examples of the many other water-imbibing materials used as disintegrants
A
- alginic acid
- carboxymethyl cellulose
- magnesium aluminium silicate
22
Q
what is alginic acid?
A
an insoluble polusaccharide
23
Q
what is carboxymethyl cellulose?
A
a soluble polysaccharide derivative
24
Q
what is magnesium aluminium silicate?
A
a mineral - Veegum
25
what are 'super-disintegrants'?
new 'processed materials'
26
state 3 examples of 'super-disintegrants'
- sodium starch glycolate
- croscarmellose type A
- crospovidone
27
describe sodium starch glycolate as a 'super-disintegrant'
- Explotab, Primojel
- cross-linked, carboxymethylated potato starch
28
what is the mechanism of sodium starch glycolate as a super-disintegrant?
- extensive swelling
- claimed to swell 100% original volume
29
describe croscarmellose type A as a super-disintegrant
- Ac-Di-Sol
- cross-linked, carboxymethylated cellulose
30
what is the mechanism of croscarmellose type A as a super-disintegrant?
fast wicking action and significant fibre swelling
31
describe crospovidone as a super-disintegrant
- Kollidon XL, polyplasdone XL
- cross-linked PVP (polyvinylpyrrolidone)
32
what is the mechanism of crospovidone as a super-disintegrant?
wicking with virtually no swelling
33
describe a graph showing the drug concentration over time for immediate release, immediate release repeated dosing, extended release and delayed release tablets
34
how does pH influence when delayed-release coated tablets dissolve?
they dissolve in higher pH of small intestine, not low pH of stomach
35
describe a graph showing the variation in drug release from delayed release Asacol tablets in varying pH environments
36
what does the FDA prescribing info for Asacol modified-release say?
there is a large inter- subject and intra- subject variability in the plasma concentrations of mesalamine and N-acetyl-5-aminosalicylic acid and in their elimination half-lives following administration of Asacol
37
how should Asacol MR tablets be taken?
- swallow Asacol tablet whole
- do not cut, break or chew the tablets
38
what has been reported by those taking Asacol MR tablets? what should patients be instructed to do?
- intact, partially intact and / or tablet shells have been reported in the stool
- instruct patients to contact their physician if this occurs repeatedly
39
what is noted in the BNF regarding other medicines affecting mesalazine?
preparations that lower stool pH (eg. lactulose_ may prevent release of mesalazine
40
give an example of a hydrophilic swelling polymer that is used as an excipient
- hydroxypropyl methylcellulose (HPMC)
41
describe the mechanism of hydrophilic swelling polymers as excipients
- matrix swelling
- followed by matrix / gel erosion
42
explain the matrix swelling stage of the mechanism of hydrophilic swelling polymer excipients. what kind of drugs is this step most important for?
- surface hydrates and creates viscous gel structure
- gel is a barrier to liquid ingress into tablet and drug diffusion out
- this stage is important for release of water-soluble drugs
43
explain the matrix / gel erosion stage of the mechanism of hydrophilic swelling polymer excipients. what kind of drugs is this step most important for?
- gradually gel matrix erodes in GIT
- this stage is important for release of water-insoluble drugs
44
state 8 examples of modified release formulations in the BNF
Madopar CR
Sinemet
Caramet
Oruvail
Voltarol
Verapress
Entocort
Colofac
45
what are Madopar CR, Sinemet and Caramet?
dopaminergic drugs used in Parkinson's
46
what is Oruvail?
drug used in rheumatic diseases and gout
47
what is dissolution?
a process where solid dissolves at the solid-liquid interface, dissolved molecules diffuse to the bulk solution
48
what are the 3 models used for describing tablet dissolution mechanisms?
- diffusion layer model
- interfacial barrier model
- Danckwert's model
49
what are the 3 stages of tablet dissolution in the order they occur?
disintegration
disaggregation
dissolution
50
what drugs is the diffusion layer model of tablet dissolution relevant for?
water-soluble drugs
51
what is another name for the diffusion layer model of drug dissolution?
Noyes-Whitney model
52
what does the diffusion layer model of tablet dissolution assume?
- that a layer of liquid, H, adjacent to the solid surface remains stagnant
- the dissolution at the solid-liquid interface is assumed to be instantaneous forming a saturated solution, Cs, of the solid in the static liquid film
53
what is the Noyes-Whitney equation?
54
what does dW / dt represent in the NW equation?
- dissolution rate
- I.e. the rate of increase of the amount of material present in solution dissolving from a solid, mass / time
55
what does k represent in the NW equation?
dissolution rate constant
56
what does Cs represent in the NW equation?
- solubility at saturation of the solvate in the bulk
- mass / volume
57
what does C represent in the NW equation?
- actual concentration of the solvate in bulk solution
- mass / volume
58
what is the formula for k in the NW equation?
- D = diffusion coefficient of the dissolved solute
- A = area of solid particle exposed to the solvent
- h = thickness of the diffusion layer
59
state 7 factors affecting drug dissolution rate
temperature
agitation
viscosity
gettability
pH
particle size
polymorphic form
60
explain temperature as a factor affecting drug dissolution rate
- affects solubility (Cs) and diffusion (D)
- often you warm up to dissolve
61
explain agitation as a factor affecting drug dissolution rate
- affects static layer (h)
- stirring of medium (eg. stirring sugar into tea)
62
explain viscosity as a factor affecting drug dissolution rate
affects diffusion (D)
63
explain wettability as a factor affecting drug dissolution rate
- affects area for drug release (A)
- eg. hydrophobic lubricant reduces gettability and hence surface area for release
64
explain pH as a factor affecting drug dissolution rate
- affects drug solubility (Cs)
- when drug has pH dependent solubility (weak acid and bases)
65
explain particle size as a factor affecting drug dissolution rate
- affects surface area (A)
- decreasing particles size improves dissolution and bioavailability of drug with poor solubility
66
what is considered poor solubility?
< 0.05 g/L
67
explain polymorphic form as a factor affecting drug dissolution rate
- different crystal structures of the same drug means different solubility
- Cs is affected
68
what is polymorphic form particularly important for as a factor affecting drug dissolution rate?
poorly soluble drugs
69
what is assumed in the interfacial barrier model of tablet dissolution?
- the process at the solid/liquid interface is not instantaneous due to a high activation free energy barrier which has to be overcome before the solid can dissolve
- once the barrier is overcome, the dissolution mechanism is essentially the same as in the diffusion layer model
70
what drugs is the interfacial barrier model for tablet dissolution relevant to?
poorly soluble drugs
71
describe the rate of diffusion in the static layer in the interfacial barrier model
rate of diffusion in the static layer is relatively fast in comparison with the surmounting of the energy barrier which therefore becomes rate limiting in the dissolution process
72
what does the Danckwert's model of tablet dissolution assume?
- packets of solvent reach the solid/liquid interface by diffusion in some random fashion
73
describe the Danckwert's model of tablet dissolution
- this model correlates with mixing of solutions
- at the interface, the packet of water is able to absorb solute according to the laws of diffusion and is then replaced by a new packet of solvent
- this surface renewal process is related to the solute transport rate and hence to the dissolution rate
74
describe the action of wetting agents as excipients regarding disintegration
- wetting agents in tablet formulation promote surface interaction with water and water penetration into tablet
- enhance disintegration
75
what can a surfactant improve regarding dissolution?
an interracially adsorbing agent (surfactant) can improve the dissolution rate by changing surface properties of drug particles
76
when are tablets evaluated to ensure their microbiological quality?
manufacture
packaging
storage
distribution
77
what is the test for uniformity of content of single-dose preparations based on?
the assay of the individual contents of active substance(s) of a number of single-dose units to determine whether the individual contents are within limits set with reference to the average content of the sample
78
describe the method for the uniformity of content test to evaluate tablets
- using a suitable analytical method, determine the individual contents of active substance(s) of 10 dosage units taken at random
- TEST A for tablets, etc formulations
79
regarding the uniformity of content test for evaluating tablets, what are the requirements for compliance and failure of the test?
- preparation complies with the test if each individual content is between 85% and 115% of the average content
- preparation fails if more than one individual content is outside these limits or if one individual content is outside the limits of 75% to 125% of the average content
80
state a quality-assurance measure assessing the disintegration of tablets
- determine in vitro whether tablets disintegrate within prescribed time placed in a liquid medium under the prescribed experimental conditions
- not a true predictor of how well the dosage form disintegrates and releases drug in vivo
81
what apparatus is used for tablet dissolution testing? why?
- vessel with a stirrer and defined dimensions
- ensures reproducibility between experiments
82
what is the tablet hardness test intended to do?
determine, under defined conditions, the resistance to crushing of tablets, measured by the force needed to disrupt them by crushing
83
what is tablet hardness important for?
water penetration and disintegration
84
what does friability testing test?
tablet resistance to abrasion
85
what is done during fragility testing of tablets?
measure the weight loss on subjecting tablets to a standard degree of agitation for a standard time
86
what are fast dissolving oral delivery formulations more commonly known as?
melts
orodispersible tablets
87
what are melts?
solid dosage forms that dissolve or disintegrate rapidly in the oral cavity resulting in solution or suspension without the need of water
88
where does the drug in melts go to when it breaks down in the mouth?
- dissolves or disperses in the saliva
- for some drugs, a portion may be absorbed from the mouth, pharynx and oesophagus as the saliva passes towards the stomach (potentially increased absorption / bioavailability)
89
what speed of dissolution is achieved by melts?
- fast dissolution of formulation in the mouth is achieved
90
how is fast dissolution of melts achieved?
- formulations are either very porous or soft moulded matrices or compressed into tablets with very low compression force
- often require specialised 'peel-off blister' packaging
91
in the GIT, where are the majority of bacteria located?
in the distal gut
92
are colonic bacteria anaerobic or aerobic?
predominantly anaerobic
93
what do colonic bacteria secrete?
enzymes capable of metabolising endogenous and exogenous substances which escape digestion in the upper GIT
94
how could drug delivery be targeted to the colon relating to colonic bacteria?
materials that are susceptible to bacterial fermentation in the colon (while remaining stable in the stomach and small intestine) could be utilised to target drug delivery to the colon
95
compare absorption potential in the small intestine and colon
colon doesn't have absorption properties as good as the small intestine but the contents is there for longer
96
state the 4 types of gastroretentive strategies
- low density system
- bioadhesive system
- expanding system
- high density system
97
describe the low density system gastroretentive strategy
- floating systems demonstrate buoyancy in the gastric media
- prerequisite: presence of stomach content
98
describe the bioadhesive system gastroretentive strategy
- exploit the mucus layer coating the stomach walls
- a major constituent of this mucus is the protein mucin which has a negative charge allowing interactions with polycations (eg. chitosan)
99
describe the expanding system gastroretentive strategy
- increase in size the stomach medium until too large to pass through the pylorus
100
state 2 limitations of the expanding system gastroretentive strategy
- potential for premature expansion in the oesophagus
- inter-patient variability in pyloric diameter
101
describe the high density system gastroretentive strategy
density higher than that of the gastric contents achieved by coating the system with heavy, inert metal allowing the system to settle in the curvature at the base of the stomach
102
what are gastroretentive strategies used for?
improving drug bioavailability by gastric retention
