Modified Release Flashcards
1
Q
L.O:
* To understand, recognise, describe and assess the strategies available for the design of modified-release drug delivery systems.
* To identify the advantages and limitations of controlled release formulations
* To understand the release profiles afforded by these mechanisms
* To distinguish between first order, zero order release kinetics of modified release formulation
* To appreciate the design variables which enable release rates to be controlled
* To identify the effects of device geometry on release profile
* Where appropriate, to quote a product which uses each mode of control above
* To deduce the likely control mechanism of modified release systems from SmPC or patient information sheets
A
2
Q
what is a MR dosage form? (and how is it different to IR)
A
Dosage forms that release drugs in a fashion other than the conventional IR
describes drug released differently from conventional
3
Q
why are MR dosage forms used over conventional IR? (3)
A
- delivering drug at specific rate/time
- extending drug release over specific duration
- delaying drug release to a pre-determined time point
4
Q
why would we delay a drug release to a pre-determined time point (2)
A
to target a drug release to a specific area
or
avoid drug release in a specific area (e.g. drugs acid labile and would be rendered inactive to stomach conditions/ drugs that irritate stomach and cause unwanted SEs)
5
Q
What are the 2 subcategories of a modified release dosage form?
A
Extended release
Delayed release
6
Q
3 subcategories within the subcategory: EXTENDED release?
A
- sustained release
- controlled release
- long acting
7
Q
What is a sustained release dosage form?(how does it work)
A
will extend the peak/time that drug is therapeutic
… prolongs duration of action
8
Q
how does sustained release differ from IR?
A
similar to IR but will continue for longer period of time, prolong action
9
Q
what does controlled release dosage form do?
A
controls amount of drug released into blood for predetermined time.
Can control plasma conc of drug in blood for that time
10
Q
long acting dosage form is a combination of what 2 types of df?
A
sustained and controlled release (the other 2 in subcategory of extended release
11
Q
What are the 2 types of delayed release dosage forms?
A
- Site specific targetting
- Enteric coating
12
Q
benefit of enteric coating?
A
protect drug from stomach/ stomach from drug
13
Q
advantages of extended release dosage forms? 4
A
- Less frequent dosing (reduce by 50%)
- More stable plasma conc than IR - Less fluctuations … better pain management
- Better px compliance
- chronotherapy - administering drug related to the body rhythm e.g. circadian rhythm (sleep wake cycle) so dont need to admin when asleep + effect maintained overnight
14
Q
What is the purpose of DELAYED release dosage forms?
A
Drug release into different location than stomach
15
Q
DELAYED release dosage forms protect?
A
acid sensitive (labile) drugs from the stomach
and
stomach from irritating drugs e.g. NSAIDs
16
Q
IR dosage form has highest/lowest drug plasma conc?
A
highest
17
Q
5 advantages of delayed release?
A
- protect labile drugs
- protect stomach from irritating drugs
- remain intact in small intestine to release drug in colon for local action
- time lag before drug release
- can also have DR followed by IR or extended release
18
Q
what advantage does MR have over IR?
A
Less SE as conc wont get to higher levels
19
Q
what is the most common design for delayed release? why?
A
enteric coating as it is pH sensitive
… will enable the drug to reach the small intestine for release in the colon
20
Q
MR advantages
A
cost effective
better convenience + compliance
lower frequency of administration
reduced side effects
Protect acid sensitive drugs, dissolve later/ elsewhere
Fluctuations in Cp eliminated
Maintains MEC over 24hrs (minimum effective conc)
21
Q
what are the different types of MR release kinetics? 3
A
zero order
first order
higuchi √ time
22
Q
what is zero order release?
A
where rate of drug release is INDEPENDANT of drug conc in dosage form, because constant conc gradient maintained
23
Q
constant conc gradient maintained between what?
and what does this influence?(zero order release)
A
barrier of dosage formulation (interface) and surrounding environments (gastric fluids).
As long as kept constant, amount of drug release also kept constant :)
24
Q
when do kinetics of a drug that follow zero order change to first? and why?
A
follow zero order until next dosing interval, the drug conc depletes, therefore changing release profile into first order
25
what kinetic order has the best control over the drug plasma concentration?
zero order
26
what order of kinetics does controlled release formulations have?
zero order
Constant amount of drug released per time
27
whats the equation of drug release with zero order?
Q = Q0 + K0 t
(Y=mx+c)
Q = amount of drug released
Q0 = initial amount of drug in solution (usually zero) if starts at origin
K0 = zero order release constant
(see graphs!!)
28
3 examples of zero order formulation designs?
- osmotic systems
- matrix tablets with poorly soluble drugs
- reservoir systems
29
what is first order release?
where rate of drug release is DEPENDANT on the drug conc in dosage form.
30
describe first order graph
Initial rapid drug release then decline in release rate (match up w amount of drug left in dosage form until eventually exhaust all of drug from it)
31
what kind of kinetics does sustained release follow?
first order release
32
how does rate of drug release change with drug conc in first order?
Rate of drug release decreases with a decrease in drug conc
33
2 examples of first order formulation designs?
conventional tablets
water soluble drugs in a porous matrix system
34
what does Higuchi of √ time release profile describe?
drug release from matrix systems
When there is a change in drug release because there is a change in distance over time that the drug molecules have to travel
35
what is the higuchi release profile?
Longer the distance (for drug mol to travel) - longer for drug to leave matrix system
So when change in distance/time… follows model
e.g. time for lecture hall people outer quicker to leave than middle
36
Other release patterns for MR? 2
Delayed release
Bimodal release
37
When is a bimodal release graph seen in dosage formulations?
in long acting formulations
38
What is the equation for zero order drug release where there is a constant drug release over time?
M infinity = Initial [ ] of drug in formulation
Ft = Kt
(check notes)
39
What is the equation for release profiles other than zero order?
Where the value of n will vary according to the type of release profile i.e. first order or higuchi
(check notes !!!)
40
What is the equation for first order release profiles?
Ft = e^Kt
Ft = fraction of dose released at time t
41
What system follows the first order release profile?
A water soluble drug in a porous matrix
42
What is the equation for higuchi release profiles?
and what systems follow it?
Ft = Kt^0.5
This is seen in systems with a matrix
43
zero order equation used for what systems?
osmotic
44
'drug conc in formulation is much higher than in surroundings' for what model?
all 3: zero, first, higuchi
45
'drug release from formulation starts fast and slows down as drug conc in formulation decreases' for which models?
first order and higuchi
...
zero order: drug release from formulation is rapid, changes to first order
46
Why are poorly soluble drugs not appropriate for MR drugs?
release of drug already delayed (rate limiting step) so making the drug MR would delay it further and make the drug show less therapeutic effect
47
4 things to consider about the MR formulation?
drug substance
disease condition
GI physiology
px
48
What 5 factors of 'drug substances' must be considered for MR dosage forms?
- sufficient solubility +permeability
- Dose: lower = better as further excipients need to be added otherwise would be too bulky
- Good GI stability: withstand harsh conditions
- Half life shouldn't be too long
49
Why should some drugs not be MR in terms of the DISEASE CONDITION that they have?
Some treatments require rapid onset/ prolonged response so long acting/combination better
E.g for diarrhoea then MR not best as you want quick action
50
MR better for acute or chronic therapy?
Good for chronic diseases where you want reduced frequency
51
Why is the GI transit time important in MR dosage forms?
GI transit time: set time, if drug not released then, will exit body without achieving active component = no therapeutic effect
52
Why is the patient's ability to use the MR product as directed so important?
reduced dosage frequency should improve px adherence as becomes more convenient to take med
do not crush: reduces therapeutic effect :(
53
why is it important to counsel your patient on MR formulations? how?
do not crush etc. so release profile for drug remains intact + subtherapeutic effects felt
by making sure px comfortable using drug/ may prefer diff formulation
54
MR lec 2
the 4 release mechanisms of ER formulations?
* Dissolution controlled formulations
* Diffusion controlled formulations
* Osmotically controlled formulations
* Ion exchange systems formulations
55
Dissolution controlled formulations
What is the dissolution mechanism of extended release formulations?
And explained by which equation?
drug solutes dissolve into the surrounding medium AKA the bulk which is explained by the Noyes Whitney equation
56
What does the dissolution of the ER drug depend on? 4
(see eqn)
- Drug solubility: higher solubility faster dissolution (thickness of boundary and how linked to drug sol)
- solvent into which the ER drug dissolves into
- particle size - Larger particles diffuse slower as they have less SA
57
How does the enteric coating control dissolution of ER drug?
polymer chosen to coat the API for ER will ensure it does not dissolve in stomach but the desired site in the GIT e.g. SI/LI
58
What are MUPS and why are they used in ER tablets?
Multiunit particulate systems
multiple sized particles. thickness = diff rates of dissolving and drug release. with MUPS can extend release of API
59
what formulation is extended release?
multiunit particluate systems (MUPS)
60
what formulations are delayed release?
MUPS or tablet with an enteric coating to prevent dissolution within the stomach
61
... How are the enteric coating of ER and DR formulations different?
both types of MRs can be MUPS but:
delayed tablets could also just be tablets as all that needs to be achieved is an enteric coating enough to protect content from stomach and later be released where needed in GIT
62
Diffusion controlled formulations:
What 3 simple factors affect the rate of diffusion?
- SA + DISTANCE that particles are moving to
- How STEEP conc gradient is
- diffusion coefficient
63
describe Diffusion controlled formulations
how it works
* Diffusion of dissolved drug controls release
* Drug dissolves in surrounding fluid
* Conc grad drives diffusion: High conc in dosage form and low outside = imbalance so moves out into fluid --> Low conc.
64
what is flux and how calculated? (see notes)
rate of diffusion.
M/t = CAKD/l
conc grad
surface area
partition coefficient
diffusion coefficient
over memb thickness
65
what are the two types of systems diffusion controlled dosage forms used?
matrix systems
reservoir systems
66
describe matrix system in an MR dosage form? + describe the kinetics involved
drug evenly dispersed within a polymer matrix = zero order.
change in conc. gradient --> first order kinetics
change in diffusion distance --> higuchi release
67
What is a matrix system in an MR dosage form?
where drug dispersed within a polymer matrix which creates a barrier between the API and the dissolution medium
68
release profile of ER with a matrix system if there is a change in concentration gradient?
first order release profile
as rate of release is dependent on the concentration of the drug
69
release profile of ER with a matrix system if there is a change in diffusion distance?
higuchi release profile
as drug release dependent on distance that drug particles moving through medium
70
what are reservoir systems? and relation to kinetics order
drug present in the core of a semi-permeable membrane
constant conc. gradient = zero order
71
why are reservoir systems zero order?
membrane acts as channel of release. Constant conc gradient over time = zero order.
when cant be maintained towards end, release profile change to first order
72
4 examples of matrix systems?
insoluble polymer matrix
soluble (erodible) polymer matrix
soluble (swellable) polymer matrix
lipid matrix
73
3 factors affecting drug release in an insoluble polymer matrix?
polymer porosity
polymer tortuosity
drug solubility
74
effect of polymer porosity on drug release in an insoluble polymer matrix?
more porous = faster solubility
75
effect of polymer tortuosity on drug release in an insoluble polymer matrix?
more torturous, slower rate of release
76
properties of suitable polymers to use in insoluble polymer matrix? + 4 examples?
Don’t dissolve or change shape in water
* Ethyl cellulose,
* Methyl acrylate metacrylate copolymer,
* Polyvinyl chloride
* Polyethylene
77
3 excipients used in insoluble polymer matrix?
* Mg stearate
* Sodium carboxymethylcellulose
* Hypromellose
78
release profile of a system with an insoluble polymer matrix?
higuchi release profile
as insolubility means water will only be able to enter through pores so API further in dosage form: take longer to dissolve than those on surface
79
what type of matrix is glucophage SR ( API meformin hydrochloride 500mg) an example of?
insoluble polymer matrix
80
Mechanism of action of a soluble (erodible) polymer matrix
Drug in water soluble polymer - dissolve + erode once in contact with fluid
-> Drug dissolution + drug diffuses through pores
Formulation size decreases (as time inc)... e.g. dipping marshmallow in water, gets smaller with time
81
2 types of erosion for soluble (erodible) polymer matrix and which soluble polymer erodes that way?
surface erosion: hydrophobic
bulk erosion: hydrophilic
82
Release profile of drugs with hydrophobic polymers?
Zero order (if completely homogenous) as undergo surface erosion = better control + drug not rapidly dissolving into the medium
83
What is the release profile of drugs with hydrophilic polymers?
First order as undergo bulk erosion.
increase in drug diffusion where rapid release then as conc decreases, release rate also depletes
84
3 factors that affect drug release from soluble polymer matrices?
* Polymer concentration
* Drug vs polymer dissolution rate
* Additional erosion from GI motility
85
what makes the following polymers suitable to be used for soluble polymer matrices?
poly lactic acid
poly vinyl caprolactone
polyethylene glycol
polyethylene glycol monostearate
they are water soluble
86
what matrix system is Tildiem SR (API Diltazem hydrochloride 90mg) an example of?
soluble polymer matrix
87
What is the MoA of a soluble (swellable) polymer matrix
drug dispersed in swellable and water soluble polymer
Water in contact with fluid - polymer swells to form a gel layer
Gel erodes and drug dissolves
88
list 4 factors that affect soluble swellable polymer matrices?
polymer hydration/ swelling rate
Rate of dissolution vs polymer swelling rate
Tortuosity and porosity of polymer gel
Polymer conc- Higher the [ ] of polymer - lower release of drug
89
why are the following polymers suitable for soluble swellable polymer matrices?
HPMC
HEC
sodium carboxymethyl cellulose
they swell in water
90
what type of matrix is cardioplen XL (API felodipine 5mg) an example of?
soluble swellable polymer matrix
91
3.
what other type of matrix system are lipid matrix systems similar to?
insoluble polymer matrix
92
MoA of lipid matrices: whys a channelling agent required? + type? + example?
as no pores in lipid matrices, water soluble channeling agent is needed e.g. NaCl so water can enter and so drug has suitable water solubility and can leave the matrix
93
API for lipid matrices need to have ...?
suitable water solubility (as dont have many channels for water ingress)
94
What is the release profile of a drug dispersed in a lipid matrix?
Higuchi - amount of drug released proportional to square root of time
95
How are reservoir systems different to matrix systems?
2 components including the core + `semi-permeable membrane
96
how does drug release occur in reservoir systems (membrane controlled)?
- drug in core surrounded by semi permeable membrane
- contact with fluid causes water ingress
- drug must diffuse through membrane
97
Where is the drug found in a reservoir system?
In core of system surrounded by a semi-permeable membrane
98
release profile of a drug dispersed in a reservoir system? why?
Zero order as long as constant number of drug molecules leaving core, you maintain a conc grad
Once gradient lost --> first order
99
3 factors that affect drug release of reservoir systems?
- Polymer thickness (semi-permeable membrane)
- Polymer porosity
- Drug solubility in GI fluids
100
why is membrane integrity crucial for reservoir systems/ what is the risk of happening if integrity is not maintained?
poor membrane integrity: risk of dose dumping which can -> toxic SE + OD
101
what formulation consideration is made to reservoir systems to avoid dose dumping?
pellets not tablets as unlikely to have all membranes compromised at once. If only few do then effect not as fatal.
MUPS - Multiple membranes
102
2 possible causes of dose dumping in reservoir systems?
poor membrane integrity
crushing tabs: rip membrane, all released at once
103
Outline how drug release occurs from osmotic systems?
- drug present in core which is osmotic agent
- core surrounded by insoluble semi permeable membrane
- build up of hydrostatic pressure
- drug pushed out through pre drilled orifice (controlled)
104
what is osmotic drug release driven by?
conc grad.
build up of HP.
controlled drug release through pre drilled orifice to push out
105
What is an osmotic system? + release kinetics?
One that contains an orifice in dosage form to ensure set number of drug mols leaving at any time which maintains zero order release
106
outline how drug is released from resin in ion exchange formulations?
- complex of insoluble resin +ionic group linked with drug
- enters acidic physiological fluid
- ion exchange occurs with competing ion from GI fluids
- drug released from resin
(image in notes)
i.e....
Complex created with drug and insoluble resin + ionic group mixed with acidic physiological fluid (hydrochloric acid)
This enables ion exchange where the drug will complex with either the acidic or alkaline resin
107
NaCl = giveaway clue to which mechanism/ system?
osmotic agent excipient thus osmotic system
108
what controls drug release in ion exchange formulations?
diffusion of ions into the resin
exchange then drug released
109
What are examples of cation exchangers? and what do they have in common?
This is where the resin ionisable group is acidic
eg sulfonic, carboxylic, phenolic
110
Where will ion exchange happen if the drug is attached to a cation exchanger?
At a higher basic pH like colon
111
What are examples of anion exchangers? and what do they have in common?
This is where the resin group is basic
eg amine or quaternary ammonium groups
112
Where will ion exchange happen when the drug is attached to an anion exchanger?
At a lower, more acidic pH like the stomach
113
check dissolution controlled form practice qs in notes !!
114
MR lec 3
which part of the Gi tract is characterised by a thick mucus layer, short residence time and low absorption?
stomach
115
which part of the GIT has a minimal mucus layer, 4-6 hr transit time, long residence time, large SA and high absorption?
small intestine
116
which part of the GIT has a long residence time, low SA, low blood perfusion, dry environment and low absorption?
large intestine
117
rank regiosn of GIT based on transit time
stomach: 0.5
SI: 4-6 hours
LI: 12-24 hours
118
What does the rate and extent of drug moving along the GIT depend on?
drug properties/ physiology of GIT:
- thickness of mucus layer - thin in the SI compared to stomach and large intestine
- SIs take up majority of GI surface - rich blood supply, long in length - more absorption than in LI which has smaller SA and perfusion
119
where are most drug and food nutrients absorbed in GIT and why?
SI: Rich blood supply on surface
Designed for nutrient and drug absorption into bloodstream = high absorption rate
120
why low absorption in LI/colon?
* Low blood perfusion: less blood vessels than SI: low absorption
* Very dry= whatever is absorbed goes into dissolution first. If something cant dissolve here, absorption wont happen.
121
What happens to drugs in the GI tract? (conventional tabs)
disintegrate -> granules + drug now in solution
Drug can then be absorbed by the gut wall + eliminated via the liver/ go -> rest of circulation for pharmacological effect
122
Where do conventional tablets get absorbed in the GIT?
SI.
(disintegrate in stomach and void in LI : polymer degraded/ API absorbed/ if insoluble matrix polymers, polymer just empty and ready to leave body whilst drug absorbed)
123
Where would disintegration of MR tablets that are for colon delivery be absorbed in GIT?
absorbed in LI
(intact in stomach and SI)
124
Where would disintegration of MR tablets that are ER, CR, SR be absorbed in the GI tract?
intact in stomach
absorbed in SI
void in LI: polymer degraded/ API absorbed/ if insoluble matrix polymers, polymer just empty and ready to leave body whilst drug absorbed
125
what formns are absorbed in SI?
conventional tabs
MR: ER, CR, SR
126
what formns are absorbed in LI?
MR: colon delivery
127
stomach reduced size of MR tabs (conventional disintegrate in stomach). effect if it hasnt?
chance being held in stomach longer than usual. Everything leaving stomach -> should have reduced in size BUT if hasn’t become smaller, may be held up in stomach and not reaching SI to absorb
= delays onset of action!
128
why do you need to advise px about eating food when taking MR tabs?
Fasting: gastric emptying of stomach every 1-2 hours.
Fed: process prolonged as stomach must force break down food and release components +drug into SI. If drug held up w food and size not released, lower part of stomach recycles dosage form, thinking of it as unbroken food particle= takes longer to get to SI.
Enteric coating: worry about the coating (acidic, remain intact in stomach- acidic environment. Higher pH in SI, coating dissolves and drug released and absorbed). Basically, don’t want drug exposed to stomach: would destroy drug/ become negatively affected by drug.
Undigested vs digested solids
129
Tabs vs caps: movement speed of MUPS (multiple unit pellet systems) vs intact tabs?
MUPS move faster
130
why do MUPS move faster than intact tabs in GIT?
don’t have to worry about size + gastric emptying factor: GE doesn’t affect MUPS as theyre smaller, more effect on single tablets.
131
Why must MR drug not be released too slowly? What excipient to add cautiously to prevent drug being released too slowly?
If all drug not absorbed quick enough, the unreleased drug will move to LI
amount of polymer used important as it can prevent drug release leading to suboptimal therapeutic effect
132
why is it important that drugs that are designed for colon delivery are not only soluble in colon chyme but in a volume of less than 50ml?
fluid volume in colon is 20-50 ml
LI: dry environment, need high drug solubility
133
what do formulations designed for colon delivery need to be stable against in the colon?
microbial degredation
lots present in colon/LI
134
3 mechanisms that can target the colon to trigger drug release?
pH
time
microbiological
135
MR colon delivery: why consider pH of coating (+integrity) used?
should not remain intact = not permeable= drug not released.
coating integrity otherwise dose dumping: so doesn’t erode. API ,has to be stable in colon environment, not the coating (as want drug release)
e.g. PPIs are degraded by acids (stomach is acidic, if give PPI w/out modification, in stomach will become inactive and no therapeutic effect)
136
Why target the colon
Local treatment of diseases e.g. IBS like ulcerative colitis
137
PH triggered drug release is achieved via use of pH sensitive polymers and can be used to coat what 3 things?
compressed tablet, pellets or beads
138
what pH sensitive polymer is appropriate for a threshold pH of...
6
7
5.6
5
4.5-4.8
eudragit L100
eudragit S100
eudragit L30-O
polyvinyl acetate pthalate
hydroxypropyl methylcellulose pthalate
139
what is the name of the dual pH and microbiota triggered coating for fail safe colonic drug release?
phloral.. used in Microbiologically triggered drug
release
140
Microbiologically triggered drug
release.. phloral... exploits what?
Exploits changes in GI pH in combination with enzymatic activity of microbiota as independent but complementary release mechanisms to guarantee site-specific release
141
Enteric coated formulations: type of disoslution
pH dependant dissolution, e.g. acidic coating will dissolve in basic environment not stomach acidic
use for DR
142
- Methyl acrylate-methacrylic acid copolymers
- Cellulose acetate succinate
- Hydroxy propyl methyl cellulose phthalate
- polyvinyl acetate phthalate (PVAP)
are all suitable polymers for enteric coating, why?
acidic polymers that dissolve as the pH of the intestine increases
143
Enteric coated formulation example?
Naprosyn EC
144
how long is gastric emptying in fasted state? + how does it compare with fed state?
1-2 hrs, longer in fed state
145
what does Type of food e.g. high fat meal vs apple juice affect?
Onset vs extent of absorption
If stay in stomach too long, affects onset of absorption but not extent because when gets to stomach, will eventually get to SI then will still say e.g. 6 hours in SI
Effect on gastric emptying slow vs fast
Effect on bile acid production and dose dumping: if have foods that secrete bile acids and taking enteric coated formulation, form will degrade and would lose drug.
146
how does GI motility look in def state and why.
which systems will absorb quicker?
Additional GI motility in fed state as stomach trying to break food into smaller parts. Matrix systems.= polymer degrade faster, quicker abs.
147
effect of alcohol on coating? GIT
degrades coating and can have dose dumping effect: lot of drug released into system in short time.
148
what is the rationale behind takign naproxen with food?
reduces gastric effects (GI irritation)
149
what is the rationale behind taking esomeprazole on an empty stomach?
faster onset
150
what is the rationale behind taking quetiapine on an empty stomach?
high fat meal significantly increases extent of absorption
151
why can Losec MUPS be taken with/out food?
small pellets granules so presence of food in stomach has no significant affect on them
152
what type of extended release formulation runs the risk of dose dumping where contents are rapidly released into the blood, leading to toxicity and death?
CR: daily dose of drug
153
Give 3 causes of dose dumping?
alcohol interactions, breaking tablets, pH interactions
154
do gastro retentive dosage formulations have an increased or decreased residence time in the stomach?
increased, usually short
155
use of gastric retention systems
increased residence time in stomach and prolong exposure in SI.
Treat conditions in stomach e.g. H. pylori infection
156
what are the 3 different design mechanisms of gastric retention systems?
floating dosage forms,
bioadhesive multiparticulates
swelling single unit systems
157
disadvantage of floating dosage forms?
on top of stomach contents.
if something in stomach prevents floating, and then leave. Similar mechanism by Gaviscon for heartburn and indigestion: create film on stomach
158
what do Bioadhesive multiparticulates do?
make mucus layer on stomach (unsuccessful in humans)
159
which design mechanism of gastric retensive nature involves polymers that swell in the stomach becoming larger than the pyloric opening and increase BA of drugs absorbed by active transport?
swelling single unit systems.
most promising design
160
Gastric retention systems involve drugs that rely on what?
carrier-mediated active transport(ers) in body for absorption. Usually located in certain parts of body e.g. stomach upper SI. If go down to LI e.g. and some drug still there, wont be absorbed.
161
Gastro-retentive dosage formulations must be(2)
* Acid stable (e.g. against microbial for enteric coating)
* Withstand motility in stomach
162
drug release testing for delayed and extended release tablets and capsules is done via what testing?
dissolution
163
Dissolution testing: pH consideration
* pH (dissolve in acidic?), agitation and timings: optimise so drug released within time dosage form will spend in GIT, especially in SI
* Use of enzymes if relevant to delivery mechanism
* May wish to compare products, batches, consider dose adjustments from conventional products
164
in relation to bioavailabiity testing, are the side effects lower for MR or IR?
MR as Cmax is lower than IR so of side effects are lower
165
dosing intervals for bioavailability testing (3)
- Size of dose
- Release rate
- Not half like IR
166
(2 bioequivalent MR formulations may not have same release mechanism why?)
... also check graphs in notes
- A matrix tab may be bioequivalent to an osmotic tab
- Can you switch between MR formulations? No because consider: RELEASE RATE and release mechanism differences. Release may be same for matrix and osmotic tab BUT release profile may differ. Would have to check
- https://bnf.nice.org.uk/drugs/diltiazem-hydrochloride/
167
Bioavailibility & Bioequivalence (modified release) 3 things to consider?
from graphs
* Cmax
* Time lag in formulation B
* Minimum effective conc (MEC)
168
why should PPIs be taken on an empty stomach? (30min before meal)
need to empty from stomach to be released and produce an effect on stomach acid secretion
169
Counselling patients
Delayed release solids
* Take with ...
glass of water/ apple juice (increases rate of gastric emptying = quicker onset of action etc. would advise with this) + on empty stomach
170
counselling points for ER solids?
* Take with glass of water/ apple juice
* Food does not sig affect bioavailability of extended release tabs and caps
* State whether the dosage form can be cut
* Don't chew or crush
* Non-erodible dosage form "ghosts" appear in the stool
* Confirm onset, frequency and storage
171
are non erodible dosage form ghosts appearing in the stool associated with delayed or extended release solids?
extended
172
does food significantly affect the bioavailability of extended release tablets and capsules?
no
173
What factors can alter the amount of drug delivered from osmotic dosage form?
Osmotic agents
Size of pre drilled orifice
Type of polymer
Conc of drug in system
Drug solubility
174
why can PLGA (common synthetic polymer for microspheres) be suitable for use to form soluble/ erodible polymer matrix systems?
not water soluble but biodegrades -> lactic + glycolic acid => normal metabolic products.
175
useful polymer to form soluble/ erodible polymer matrix systems?
PLGA
176
For drugs that are not stable in the GIT, modified release can still be achieved how?
other ROA eg parenteral
177
Clinical consequences of admin depot formulation like prostap IV as bolus injection (suspension, supposed to be IM/SC only)
o Rapid+ dangerous release of lot of drug to bloodstream -> toxic/ AEs
o Lack of sustained release
Potential disruption of microsphere matrix, - affect intended release profile of the drug and efficacy
178
why are suspensions not appropriate for IV administration?
risk of particle embolism, -> serious adverse events
