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Lab 3 > Modified Release > Flashcards

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
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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

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3
Q

why are MR dosage forms used over conventional IR? (3)

A
  1. delivering drug at specific rate/time
  2. extending drug release over specific duration
  3. delaying drug release to a pre-determined time point
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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)

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5
Q

What are the 2 subcategories of a modified release dosage form?

A

Extended release

Delayed release

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6
Q

3 subcategories within the subcategory: EXTENDED release?

A
  • sustained release
  • controlled release
  • long acting
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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

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8
Q

how does sustained release differ from IR?

A

similar to IR but will continue for longer period of time, prolong action

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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

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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

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11
Q

What are the 2 types of delayed release dosage forms?

A
  • Site specific targetting
  • Enteric coating
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12
Q

benefit of enteric coating?

A

protect drug from stomach/ stomach from drug

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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
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14
Q

What is the purpose of DELAYED release dosage forms?

A

Drug release into different location than stomach

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15
Q

DELAYED release dosage forms protect?

A

acid sensitive (labile) drugs from the stomach
and
stomach from irritating drugs e.g. NSAIDs

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16
Q

IR dosage form has highest/lowest drug plasma conc?

A

highest

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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
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18
Q

what advantage does MR have over IR?

A

Less SE as conc wont get to higher levels

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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

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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)

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21
Q

what are the different types of MR release kinetics? 3

A

zero order
first order
higuchi √ time

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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

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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 :)

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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

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25
Q

what kinetic order has the best control over the drug plasma concentration?

A

zero order

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26
Q

what order of kinetics does controlled release formulations have?

A

zero order
Constant amount of drug released per time

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27
Q

whats the equation of drug release with zero order?

A

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!!)

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28
Q

3 examples of zero order formulation designs?

A
  • osmotic systems
  • matrix tablets with poorly soluble drugs
  • reservoir systems
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29
Q

what is first order release?

A

where rate of drug release is DEPENDANT on the drug conc in dosage form.

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30
Q

describe first order graph

A

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)

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31
Q

what kind of kinetics does sustained release follow?

A

first order release

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32
Q

how does rate of drug release change with drug conc in first order?

A

Rate of drug release decreases with a decrease in drug conc

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33
Q

2 examples of first order formulation designs?

A

conventional tablets
water soluble drugs in a porous matrix system

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34
Q

what does Higuchi of √ time release profile describe?

A

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

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35
Q

what is the higuchi release profile?

A

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

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36
Q

Other release patterns for MR? 2

A

Delayed release
Bimodal release

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37
Q

When is a bimodal release graph seen in dosage formulations?

A

in long acting formulations

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38
Q

What is the equation for zero order drug release where there is a constant drug release over time?

A

M infinity = Initial [ ] of drug in formulation

Ft = Kt

(check notes)

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39
Q

What is the equation for release profiles other than zero order?

A

Where the value of n will vary according to the type of release profile i.e. first order or higuchi

(check notes !!!)

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40
Q

What is the equation for first order release profiles?

A

Ft = e^Kt

Ft = fraction of dose released at time t

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41
Q

What system follows the first order release profile?

A

A water soluble drug in a porous matrix

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42
Q

What is the equation for higuchi release profiles?
and what systems follow it?

A

Ft = Kt^0.5

This is seen in systems with a matrix

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43
Q

zero order equation used for what systems?

A

osmotic

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44
Q

‘drug conc in formulation is much higher than in surroundings’ for what model?

A

all 3: zero, first, higuchi

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45
Q

‘drug release from formulation starts fast and slows down as drug conc in formulation decreases’ for which models?

A

first order and higuchi
…
zero order: drug release from formulation is rapid, changes to first order

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46
Q

Why are poorly soluble drugs not appropriate for MR drugs?

A

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

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47
Q

4 things to consider about the MR formulation?

A

drug substance
disease condition
GI physiology
px

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48
Q

What 5 factors of ‘drug substances’ must be considered for MR dosage forms?

A
  • 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
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49
Q

Why should some drugs not be MR in terms of the DISEASE CONDITION that they have?

A

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

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50
Q

MR better for acute or chronic therapy?

A

Good for chronic diseases where you want reduced frequency

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51
Q

Why is the GI transit time important in MR dosage forms?

A

GI transit time: set time, if drug not released then, will exit body without achieving active component = no therapeutic effect

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52
Q

Why is the patient’s ability to use the MR product as directed so important?

A

reduced dosage frequency should improve px adherence as becomes more convenient to take med

do not crush: reduces therapeutic effect :(

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53
Q

why is it important to counsel your patient on MR formulations? how?

A

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

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54
Q

MR lec 2

the 4 release mechanisms of ER formulations?

A
  • Dissolution controlled formulations
  • Diffusion controlled formulations
  • Osmotically controlled formulations
  • Ion exchange systems formulations
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55
Q

Dissolution controlled formulations
What is the dissolution mechanism of extended release formulations?
And explained by which equation?

A

drug solutes dissolve into the surrounding medium AKA the bulk which is explained by the Noyes Whitney equation

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56
Q

What does the dissolution of the ER drug depend on? 4

A

(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
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57
Q

How does the enteric coating control dissolution of ER drug?

A

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

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58
Q

What are MUPS and why are they used in ER tablets?

A

Multiunit particulate systems
multiple sized particles. thickness = diff rates of dissolving and drug release. with MUPS can extend release of API

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59
Q

what formulation is extended release?

A

multiunit particluate systems (MUPS)

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60
Q

what formulations are delayed release?

A

MUPS or tablet with an enteric coating to prevent dissolution within the stomach

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61
Q

… How are the enteric coating of ER and DR formulations different?

A

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

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62
Q

Diffusion controlled formulations:

What 3 simple factors affect the rate of diffusion?

A
  • SA + DISTANCE that particles are moving to
  • How STEEP conc gradient is
  • diffusion coefficient
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63
Q

describe Diffusion controlled formulations
how it works

A
  • 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.
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64
Q

what is flux and how calculated? (see notes)

A

rate of diffusion.
M/t = CAKD/l

conc grad
surface area
partition coefficient
diffusion coefficient
over memb thickness

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65
Q

what are the two types of systems diffusion controlled dosage forms used?

A

matrix systems
reservoir systems

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66
Q

describe matrix system in an MR dosage form? + describe the kinetics involved

A

drug evenly dispersed within a polymer matrix = zero order.

change in conc. gradient –> first order kinetics

change in diffusion distance –> higuchi release

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67
Q

What is a matrix system in an MR dosage form?

A

where drug dispersed within a polymer matrix which creates a barrier between the API and the dissolution medium

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68
Q

release profile of ER with a matrix system if there is a change in concentration gradient?

A

first order release profile
as rate of release is dependent on the concentration of the drug

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69
Q

release profile of ER with a matrix system if there is a change in diffusion distance?

A

higuchi release profile
as drug release dependent on distance that drug particles moving through medium

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70
Q

what are reservoir systems? and relation to kinetics order

A

drug present in the core of a semi-permeable membrane
constant conc. gradient = zero order

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71
Q

why are reservoir systems zero order?

A

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

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72
Q

4 examples of matrix systems?

A

insoluble polymer matrix
soluble (erodible) polymer matrix
soluble (swellable) polymer matrix
lipid matrix

73
Q

3 factors affecting drug release in an insoluble polymer matrix?

A

polymer porosity
polymer tortuosity
drug solubility

74
Q

effect of polymer porosity on drug release in an insoluble polymer matrix?

A

more porous = faster solubility

75
Q

effect of polymer tortuosity on drug release in an insoluble polymer matrix?

A

more torturous, slower rate of release

76
Q

properties of suitable polymers to use in insoluble polymer matrix? + 4 examples?

A

Don’t dissolve or change shape in water
* Ethyl cellulose,
* Methyl acrylate metacrylate copolymer,
* Polyvinyl chloride
* Polyethylene

77
Q

3 excipients used in insoluble polymer matrix?

A
  • Mg stearate
  • Sodium carboxymethylcellulose
  • Hypromellose
78
Q

release profile of a system with an insoluble polymer matrix?

A

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
Q

what type of matrix is glucophage SR ( API meformin hydrochloride 500mg) an example of?

A

insoluble polymer matrix

80
Q

Mechanism of action of a soluble (erodible) polymer matrix

A

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
Q

2 types of erosion for soluble (erodible) polymer matrix and which soluble polymer erodes that way?

A

surface erosion: hydrophobic

bulk erosion: hydrophilic

82
Q

Release profile of drugs with hydrophobic polymers?

A

Zero order (if completely homogenous) as undergo surface erosion = better control + drug not rapidly dissolving into the medium

83
Q

What is the release profile of drugs with hydrophilic polymers?

A

First order as undergo bulk erosion.
increase in drug diffusion where rapid release then as conc decreases, release rate also depletes

84
Q

3 factors that affect drug release from soluble polymer matrices?

A
  • Polymer concentration
  • Drug vs polymer dissolution rate
  • Additional erosion from GI motility
85
Q

what makes the following polymers suitable to be used for soluble polymer matrices?

poly lactic acid
poly vinyl caprolactone
polyethylene glycol
polyethylene glycol monostearate

A

they are water soluble

86
Q

what matrix system is Tildiem SR (API Diltazem hydrochloride 90mg) an example of?

A

soluble polymer matrix

87
Q

What is the MoA of a soluble (swellable) polymer matrix

A

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
Q

list 4 factors that affect soluble swellable polymer matrices?

A

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
Q

why are the following polymers suitable for soluble swellable polymer matrices?

HPMC
HEC
sodium carboxymethyl cellulose

A

they swell in water

90
Q

what type of matrix is cardioplen XL (API felodipine 5mg) an example of?

A

soluble swellable polymer matrix

91
Q
  1. what other type of matrix system are lipid matrix systems similar to?
A

insoluble polymer matrix

92
Q

MoA of lipid matrices: whys a channelling agent required? + type? + example?

A

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
Q

API for lipid matrices need to have …?

A

suitable water solubility (as dont have many channels for water ingress)

94
Q

What is the release profile of a drug dispersed in a lipid matrix?

A

Higuchi - amount of drug released proportional to square root of time

95
Q

How are reservoir systems different to matrix systems?

A

2 components including the core + `semi-permeable membrane

96
Q

how does drug release occur in reservoir systems (membrane controlled)?

A
  • drug in core surrounded by semi permeable membrane
  • contact with fluid causes water ingress
  • drug must diffuse through membrane
97
Q

Where is the drug found in a reservoir system?

A

In core of system surrounded by a semi-permeable membrane

98
Q

release profile of a drug dispersed in a reservoir system? why?

A

Zero order as long as constant number of drug molecules leaving core, you maintain a conc grad

Once gradient lost –> first order

99
Q

3 factors that affect drug release of reservoir systems?

A
  • Polymer thickness (semi-permeable membrane)
  • Polymer porosity
  • Drug solubility in GI fluids
100
Q

why is membrane integrity crucial for reservoir systems/ what is the risk of happening if integrity is not maintained?

A

poor membrane integrity: risk of dose dumping which can -> toxic SE + OD

101
Q

what formulation consideration is made to reservoir systems to avoid dose dumping?

A

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
Q

2 possible causes of dose dumping in reservoir systems?

A

poor membrane integrity
crushing tabs: rip membrane, all released at once

103
Q

Outline how drug release occurs from osmotic systems?

A
  • 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
Q

what is osmotic drug release driven by?

A

conc grad.
build up of HP.
controlled drug release through pre drilled orifice to push out

105
Q

What is an osmotic system? + release kinetics?

A

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
Q

outline how drug is released from resin in ion exchange formulations?

A
  • 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
Q

NaCl = giveaway clue to which mechanism/ system?

A

osmotic agent excipient thus osmotic system

108
Q

what controls drug release in ion exchange formulations?

A

diffusion of ions into the resin
exchange then drug released

109
Q

What are examples of cation exchangers? and what do they have in common?

A

This is where the resin ionisable group is acidic
eg sulfonic, carboxylic, phenolic

110
Q

Where will ion exchange happen if the drug is attached to a cation exchanger?

A

At a higher basic pH like colon

111
Q

What are examples of anion exchangers? and what do they have in common?

A

This is where the resin group is basic
eg amine or quaternary ammonium groups

112
Q

Where will ion exchange happen when the drug is attached to an anion exchanger?

A

At a lower, more acidic pH like the stomach

113
Q

check dissolution controlled form practice qs in notes !!

A
114
Q

MR lec 3

which part of the Gi tract is characterised by a thick mucus layer, short residence time and low absorption?

A

stomach

115
Q

which part of the GIT has a minimal mucus layer, 4-6 hr transit time, long residence time, large SA and high absorption?

A

small intestine

116
Q

which part of the GIT has a long residence time, low SA, low blood perfusion, dry environment and low absorption?

A

large intestine

117
Q

rank regiosn of GIT based on transit time

A

stomach: 0.5
SI: 4-6 hours
LI: 12-24 hours

118
Q

What does the rate and extent of drug moving along the GIT depend on?

A

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
Q

where are most drug and food nutrients absorbed in GIT and why?

A

SI: Rich blood supply on surface
Designed for nutrient and drug absorption into bloodstream = high absorption rate

120
Q

why low absorption in LI/colon?

A
  • 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
Q

What happens to drugs in the GI tract? (conventional tabs)

A

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
Q

Where do conventional tablets get absorbed in the GIT?

A

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
Q

Where would disintegration of MR tablets that are for colon delivery be absorbed in GIT?

A

absorbed in LI
(intact in stomach and SI)

124
Q

Where would disintegration of MR tablets that are ER, CR, SR be absorbed in the GI tract?

A

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
Q

what formns are absorbed in SI?

A

conventional tabs
MR: ER, CR, SR

126
Q

what formns are absorbed in LI?

A

MR: colon delivery

127
Q

stomach reduced size of MR tabs (conventional disintegrate in stomach). effect if it hasnt?

A

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
Q

why do you need to advise px about eating food when taking MR tabs?

A

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
Q

Tabs vs caps: movement speed of MUPS (multiple unit pellet systems) vs intact tabs?

A

MUPS move faster

130
Q

why do MUPS move faster than intact tabs in GIT?

A

don’t have to worry about size + gastric emptying factor: GE doesn’t affect MUPS as theyre smaller, more effect on single tablets.

131
Q

Why must MR drug not be released too slowly? What excipient to add cautiously to prevent drug being released too slowly?

A

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
Q

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?

A

fluid volume in colon is 20-50 ml
LI: dry environment, need high drug solubility

133
Q

what do formulations designed for colon delivery need to be stable against in the colon?

A

microbial degredation
lots present in colon/LI

134
Q

3 mechanisms that can target the colon to trigger drug release?

A

pH
time
microbiological

135
Q

MR colon delivery: why consider pH of coating (+integrity) used?

A

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
Q

Why target the colon

A

Local treatment of diseases e.g. IBS like ulcerative colitis

137
Q

PH triggered drug release is achieved via use of pH sensitive polymers and can be used to coat what 3 things?

A

compressed tablet, pellets or beads

138
Q

what pH sensitive polymer is appropriate for a threshold pH of…
6
7
5.6
5
4.5-4.8

A

eudragit L100
eudragit S100
eudragit L30-O
polyvinyl acetate pthalate
hydroxypropyl methylcellulose pthalate

139
Q

what is the name of the dual pH and microbiota triggered coating for fail safe colonic drug release?

A

phloral.. used in Microbiologically triggered drug
release

140
Q

Microbiologically triggered drug
release.. phloral… exploits what?

A

Exploits changes in GI pH in combination with enzymatic activity of microbiota as independent but complementary release mechanisms to guarantee site-specific release

141
Q

Enteric coated formulations: type of disoslution

A

pH dependant dissolution, e.g. acidic coating will dissolve in basic environment not stomach acidic
use for DR

142
Q
  • 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?

A

acidic polymers that dissolve as the pH of the intestine increases

143
Q

Enteric coated formulation example?

A

Naprosyn EC

144
Q

how long is gastric emptying in fasted state? + how does it compare with fed state?

A

1-2 hrs, longer in fed state

145
Q

what does Type of food e.g. high fat meal vs apple juice affect?

A

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
Q

how does GI motility look in def state and why.
which systems will absorb quicker?

A

Additional GI motility in fed state as stomach trying to break food into smaller parts. Matrix systems.= polymer degrade faster, quicker abs.

147
Q

effect of alcohol on coating? GIT

A

degrades coating and can have dose dumping effect: lot of drug released into system in short time.

148
Q

what is the rationale behind takign naproxen with food?

A

reduces gastric effects (GI irritation)

149
Q

what is the rationale behind taking esomeprazole on an empty stomach?

A

faster onset

150
Q

what is the rationale behind taking quetiapine on an empty stomach?

A

high fat meal significantly increases extent of absorption

151
Q

why can Losec MUPS be taken with/out food?

A

small pellets granules so presence of food in stomach has no significant affect on them

152
Q

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?

A

CR: daily dose of drug

153
Q

Give 3 causes of dose dumping?

A

alcohol interactions, breaking tablets, pH interactions

154
Q

do gastro retentive dosage formulations have an increased or decreased residence time in the stomach?

A

increased, usually short

155
Q

use of gastric retention systems

A

increased residence time in stomach and prolong exposure in SI.
Treat conditions in stomach e.g. H. pylori infection

156
Q

what are the 3 different design mechanisms of gastric retention systems?

A

floating dosage forms,
bioadhesive multiparticulates
swelling single unit systems

157
Q

disadvantage of floating dosage forms?

A

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
Q

what do Bioadhesive multiparticulates do?

A

make mucus layer on stomach (unsuccessful in humans)

159
Q

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?

A

swelling single unit systems.
most promising design

160
Q

Gastric retention systems involve drugs that rely on what?

A

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
Q

Gastro-retentive dosage formulations must be(2)

A
  • Acid stable (e.g. against microbial for enteric coating)
  • Withstand motility in stomach
162
Q

drug release testing for delayed and extended release tablets and capsules is done via what testing?

A

dissolution

163
Q

Dissolution testing: pH consideration

A
  • 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
Q

in relation to bioavailabiity testing, are the side effects lower for MR or IR?

A

MR as Cmax is lower than IR so of side effects are lower

165
Q

dosing intervals for bioavailability testing (3)

A
  • Size of dose
  • Release rate
  • Not half like IR
166
Q

(2 bioequivalent MR formulations may not have same release mechanism why?)
… also check graphs in notes

A
  • 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
Q

Bioavailibility & Bioequivalence (modified release) 3 things to consider?
from graphs

A
  • Cmax
  • Time lag in formulation B
  • Minimum effective conc (MEC)
168
Q

why should PPIs be taken on an empty stomach? (30min before meal)

A

need to empty from stomach to be released and produce an effect on stomach acid secretion

169
Q

Counselling patients
Delayed release solids
* Take with …

A

glass of water/ apple juice (increases rate of gastric emptying = quicker onset of action etc. would advise with this) + on empty stomach

170
Q

counselling points for ER solids?

A
  • 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
Q

are non erodible dosage form ghosts appearing in the stool associated with delayed or extended release solids?

A

extended

172
Q

does food significantly affect the bioavailability of extended release tablets and capsules?

A

no

173
Q

What factors can alter the amount of drug delivered from osmotic dosage form?

A

Osmotic agents
Size of pre drilled orifice
Type of polymer
Conc of drug in system
Drug solubility

174
Q

why can PLGA (common synthetic polymer for microspheres) be suitable for use to form soluble/ erodible polymer matrix systems?

A

not water soluble but biodegrades -> lactic + glycolic acid => normal metabolic products.

175
Q

useful polymer to form soluble/ erodible polymer matrix systems?

A

PLGA

176
Q

For drugs that are not stable in the GIT, modified release can still be achieved how?

A

other ROA eg parenteral

177
Q

Clinical consequences of admin depot formulation like prostap IV as bolus injection (suspension, supposed to be IM/SC only)

A

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
Q

why are suspensions not appropriate for IV administration?

A

risk of particle embolism, -> serious adverse events

Lab 3 (21 decks)

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