Solutions, Colloids & Suspensions Flashcards
(227 cards)
1
Q
What is meant by Active Pharmaceutical Ingredient, API?
A
- substance intended to have pharmacological activity or
- have a direct effect in diagnosis, cure, treatment etc of disease or
- to have direct effect in restoring, correcting or modifying physiological functions
2
Q
Excipient meaning?
A
Any component in medicinal product other than active ingredient
3
Q
Formulation meaning?
A
A means of administering drugs to the body in safe, efficient, accurate etc manner
4
Q
What three areas does formulation improve?
A
- Patient compliance
- API stability
- Pharmacokinetic profile
5
Q
How can poor formulation affect activity?
A
HIGH drug-excipient interaction = poor release
LOW drug-excipient interaction = dump dosing
6
Q
What is meant by ‘invasive’ delivery routes?
A
Methods of drug delivery that access the target via physical trauma e.g. to the skin
7
Q
What is meant by ‘non-invasive’ delivery routes?
A
Methods of drug delivery that access the target without physical damage to the tissue e.g. via crossing epithelium lining organs, mucous membranes etc
8
Q
What is meant by systemic delivery?
A
Drug enters circulation and is transported around the body
9
Q
How do drugs delivered systemically reach their intended targets?
A
- transported to tissues via RBF (regional blood flow)
- diffuses from blood to target
10
Q
What is a benefit to systemic drug delivery?
A
Can target sites inaccessible by local application e.g. myocardium, brain
11
Q
What are some disadvantages to systemic drug delivery?
A
- some sites served poorly by RBF e.g. joint capsules, epidermis
- high doses needed
- non-specific dosing of other tissues occurs, can cause side effects
12
Q
What is meant by local delivery?
A
Drug administered at or close to target site
13
Q
What are the advantages of local drug delivery?
A
- drug restricted to area of application
- rapid onset
- reduced dose
- reduced metabolism (avoids first pass metabolism)
14
Q
What are the disadvantages of local drug delivery?
A
- some tissues difficult to deliver to
- transfer/spread of drug can occur
15
Q
What is the buccal delivery route?
A
Topical route by which drugs are held between the cheek and gum to be distributed through oral mucosa
16
Q
What is the pulmonary drug delivery route?
A
Patients use an inhaler and medications are absorbed into the bloodstream via lung mucous membrane
17
Q
What is bioavailability?
A
The fraction of unchanged drug reaching the systemic circulation by any route
18
Q
What is the % bioavailability following an IV injection?
A
100%
19
Q
Why is bioavailability via oral route not usually 100%?
A
- poor absorption
- first pass metabolism
20
Q
What factors of an entire dose of orally-delivered drug must be met to ensure 100% bioavailability?
A
- be completely released from dosage form
- be fully dissolved into molecular form in GI fluids
- be stable in GI fluids
- pass through GI barrier without metabolising
- pass through liver without metabolising
21
Q
What does a pharmacokinetic profile of a drug show?
A
Varying concentration in systemic circulation
22
Q
What is Cmax on a pharmacokinetic profile?
A
Maximum concentration of a drug in the body following administration
23
Q
What is the aim of a dosage regimen?
A
To maintain constant therapeutic plasma concentration for the duration of the therapy
24
Q
What are the effects of poor patient compliance or low-quality formulations on dosage regimens?
A
- irregular dosing
Can cause sub-optimal plasma concentrations
25
What sorts of formulations can be used to deliver and maintain consistent drug levels in the circulation?
1. Transdermal patch
2. Modified release tablets
3. Depot injections
26
How do IV injections, tablets and oral solutions compare in terms of speed of onset of action?
IV injection > oral solution > tablets
27
Why are tablets slower in terms of speed of onset of action compared to oral solutions?
Drug must be released from tablets then dissolve in GI fluids before crossing GI mucosa and entering systemic circulation
28
What factors should be considered to ensure patient compliance when selecting a formulation?
1. Discomfort e.g. injections unpopular
2. Convenience - self admin and simple regimes better
3. Taste/odour
4. Appearance e.g. colour can affect view of quality
5. Cost - expensive formulation = expensive product
29
Why are excipients included?
To produce a functional formulation, work around the active ingredient(s)
30
What factors should be considered when selecting excipients?
- irritants/toxicity
- compatibility with API/packaging/other excipients
- stability
- colour, flavour, smell
- cost
31
When should adding a preservative (excipient) be considered?
- for all preparations not for immediate use
- especially when water and or natural products are present
32
What are good characteristics for potential preservatives?
- high water solubility (low o/w partition coefficient)
33
What are some consequences to a formulation of microbial contamination?
- hazard to health
- odours or discolouration
- pH changes
34
What are commonly used viscosity modifiers as excipients?
How do they affect viscosity?
- polysaccharides
- water-soluble celluloses
- hydrated silicas
Increase
35
How does density affect a formulation?
The smaller the density difference between phases, the less sedimentation will occur
36
What are some common density modifiers used as excipients?
What are their limitations?
- sucrose
- glycerol
- propylene glycol
Work over limited temperature range
37
Why are antioxidants often included as excipients?
Oils are susceptible to oxidation, can cause rancidity
Antioxidants will slow the oxidation process
38
What is rancidity from oil oxidation?
Why is rancidity bad?
- fatty acid esters become free fatty acids
- rancid oils contain potentially carcinogenic free radicals
39
What is a preferable characteristic of an antioxidant?
Oil soluble
40
What is the role of buffers as excipients?
Influence
- chemical stability
- tonicity
- physiological compatibility
41
What are organoleptic substances?
Act upon the senses e.g. flavourings, colourants, sweeteners
42
For what are organoleptic substances commonly used?
To mask the taste of oily drugs in emulsions
43
What can synthetic sweeteners affect in a formulation? Why?
Flocculation because they are often salts
44
What is the role of humectants in formulations?
What should be considered when adding humectants?
Decrease evaporation of water either from formulation in container or while in use
High concentration will remove water from skin
45
What are some examples of humectants as excipients?
Propylene glycol
Glycerol
Sorbitol
46
Why are sweeteners with high sugar concs potentially a bad idea?
- could be inappropriate for diabetic patients
- affects rheology (flow) of product
47
What is the definition of solution?
A mixture of two or more components that forms a single phase which is homogenous down to the molecular level (monophasic)
48
What is the definition of solute?
Component which is dispersed as discrete molecules/ions in the solvent
49
What is a disperse system containing a solid dispersed phase called?
A suspension
50
What is a disperse system?
Mixture consisting of 2 or more components in a heterogeneous mixture (disperse phase and continuous phase)
51
What is a disperse system with a liquid dispersed phase called?
Emulsion
52
What are the benefits to using a solution as a dosage form?
- drug in molecular form so rapid onset of action. (ESP. Parenteral delivery)
- no dissolution required so rapid uptake following delivery
- homogenous allowing for precise and tailored dosing
- easy to swallow
- straightforward manufacture
53
What are some disadvantages to choosing a solution as a drug form?
- some drugs unstable in solution
- not all drugs have adequate aqueous solubility to make a suitably potent solution
- generally heavier and take up more space than solid oral dosage forms so increased cost and reduced convenience
- challenging packaging
54
What is dissolution?
Transfer of molecules/ions from solid state into solution
55
How does dissolution happen?
Forces that bind adjacent solute molecules together are overcome by attractive forces of molecules of solvent
Liberated molecule comes solvated - surrounded by solvent molecules in solvation shell
56
What three forces/interactions must we be aware of during dissolution?
Solute-solute
Solvent-solvent
Solute-solvent
57
What happens if solvent/solvent forces are too strong?
Solvent molecules stick together so no space made for solute molecules therefore no dissolution
58
What happens if the solute/solute forces are very strong?
Solute will not break apart, solute molecules cannot be liberated for dissolution
59
How can the rate of dissolution be sped up?
- adding heat
- kinetic energy increase
- ultrasonication (transmission of ultrasound waves through liquid)
60
What is the definition of solubility?
How is it expressed?
Extent to which dissolution proceeds under a given set of experimental conditions
Expressed as maximum of in given conditions eg. %w/v, w/w, v/v
61
What is meant by miscibility?
The ability of one liquid to completely dissolve on another liquid solvent
62
What is a saturated solution?
Solution in which no more solvent molecules are available to form salvation shells
63
How does temperature affect solubility?
Higher temperature = higher solubility
64
What are the possible consequences of storing certain solutions at too cool a temperature?
- precipitation of solute which can cause
- irreversible damage to formulation
Taking a dose from a solution containing precipitated active will lead to underdosing
65
What does solubility convey?
The maximum amount of solute that can be dissolved in the solvent
66
How is solubility measured/how are solvent/temperature conditions defined?
1. Pure solute added to solvent to create saturated solution (long mixing time or heating then cooling)
2. Centrifugation separates undissolved solute
3. Supernatant collected, may be diluted for analysis to determine amount of solute present e.g. via UV spec, HPLC
4. Replicates performed to determine accurate value
67
What factors can affect drug solubility?
- molecular structure (FG polarity)
- logP value
- drug ionisation
- drug salts (ionic state can be manipulated to suit route of administration)
- solution pH
68
Why is the free base/acid form used for topical drug delivery?
Lipophilic form will penetrate lipophilic environment of the skin
69
Counterions of drugs in their salt form have no pharmacological action but may affect what?
- ion pair association constant (annoy be too strong)
- toxicity levels of counter ion in formulation
- interactions with excipients/packaging e.g. Cl- is corrosive
70
Drug molecules arranged into a regular pattern are called what?
Crystalline
71
Drug molecules arranged randomly are called what?
Amorphous
72
Drug molecules with multiple crystalline arrangements are called what?
Polymorphic
73
Why can polymorphism create issues in formulation?
Different crystalline forms have different rates of dissolution, stability in storage etc
74
How can poor solubilisation be improved?
- choice of solvent
- employing a cosolvent
- using different drug salt
- manipulation of solution pH
- couple action of cyclodextrins
- producing a different formulation type
75
Why are lipophilic solvents rarely used for oral delivery?
- poor taste
- toxicity
- irritany
- lack of miscibility with physiological fluids
76
What types of formulations can lipophilic solvents be useful in?
- parenteral (depot injections)
- topical formulations
77
What are some examples of non-aqueous solvents?
- alcohols e.g. ethanol, propylene glycol
- fixed vegetable oils
- esters
- dimethyl sulfoxide (DMSO)
78
What is a co-solvent?
A drug is dissolved in a more lipophilic solvent and the resulting solution is mixed with water
79
Why might multiple co-solvents be used?
To maximise the solubility of the drug and optimise efficacy, stability etc of solution
80
A co-solvent must be what?
Miscible with water
81
What is the most commonly used alcohol as a co-solvent?
Ethanol
82
Phenobarbitone is virtually insoluble in water so how can it be made into a clear product?
- dissolving in ethanol
- diluting with glycerol and water
83
What is the indication for phenobarbitone?
Control of seizures
84
Methyl hydroxybenzoate is a preservative in many oral medications with poor water solubility. How is it added?
By dissolving in propylene glycol
85
What are polyethylene glycols?
Long chain polyethers that can be employed as co-solvents
General structure HO-CH2-(CH2-O-CH2)n-CH2-OH
Where if n < 400 then liquid, > then solid
86
What is the most common PEG?
PEG400
87
When manipulating the pH of a solution for use in meds what must be considered?
Balancing dilution of formulation (weak acids/bases) vs. Degradation of drug or excipient (strong //)
88
What is the working range of the buffer Hydrochloric acid + sodium citrate?
PH 1-5
89
What is the working range of the buffer Borax + sodium hydroxide?
PH 9.2-11
90
What are cyclodextrins?
What is their structure?
Semi-synthetic polysaccharides made up of glucose molecules bound together in a cyclic ‘bottomless bucket’ structure
- hydrophobic interior (HC)
- hydrophilic exterior (hydroxyls)
91
How does the type of glucose molecules in cyclodextrins affect their structure?
Alpha - 6 molecules
Beta - 7 molecules
Gamma - 8 molecules
Have different cavity sizes
92
What do cyclodextrins form? What does this allow?
When does it work best?
Guest-host inclusion complexes
- allows dissolution by increasing the aqueous solubility of the guest molecule
Works best when drug molecules have
- lipophilic moiety
- correct size to fit cavity
93
What does the use of guest-host inclusion complexes rely on with regards to drugs reaching their targets?
Dissociation at target membrane
94
What are two other examples of excipient types that may be added to ensure manufacture success/drug compliance etc?
- isotonicity adjusters
- chelating agents
95
In colloids and suspensions, what sorts of particles make up the disperse and continuous phases?
disperse - solid
continuous - liquid
96
What size are the particles in a colloidal dispersion?
How can colloids be distinguished from solutions?
1nm - 1micrometer in diameter (cannot see)
distinguish because of effect that dispersed phase has on light
97
How do colloids differ from suspensions (coarse dispersions) ?
How can the different phases in a colloid be separated?
particles in colloid too small for gravity to have an effect therefore cannot settle
must be separated by centrifugation
98
Why will the particles in a colloid diffuse?
move by random Brownian motion
99
What are some examples of colloids?
milk, blood (plasma proteins not RBC as they settle with time)
100
What are coarse dispersions AKA?
What are the size of the particles in a coarse dispersion?
suspensions
>1 micrometer diameter
101
What must be considered when designing a formulation as a suspension?
- large particles are liable to sedimentation
- formulation must be designed to ensure sedimentation can be reversed e.g. by shaking (energy input)
- sedimentation must be slow enough that a homogeneous dose can be obtained e.g. in syringe, following shaking
102
why are suspensions unsuitable for certain injection formulations?
particle size dictates delivery route - capillary diameter is 8-10 micrometers
103
What are the advantages to disperse systems?
- suitable for drugs susceptible to aqueous degradation
- increased absorption speed compared to solid oral dose
- high SA of active, good for absorption (particle size can be tailored for absorption)
- allows flexibility of formulation e.g. taste masking
104
What are the disadvantages to disperse systems?
- accurate dosing cannot be assured if not shaken properly before each use
(same for all liquid formulations)
- stability problems of API/excipients
- liquids susceptible to microbial contamination
- size/weight/packaging issues
- more difficult to mask taste in liquid than solid
105
Why do particles in suspension have little taste?
particles >10 micrometers cannot enter taste bud pore,
only individual molecules can interact with gustatory cells to elicit response
106
What are some properties of an ideal disperse system?
- even distribution of particles throughout continuous phase
- relatively slow sedimentation rate
- easy re-dispersal of sediment
- easy flow from container
- small and uniform particle size
107
How can colloid systems be classified?
Into what three classes?
based on interaction with dispersed and continuous phases
1. lyophobic - solvent 'hating'
2. lyophilic - solvent 'loving'
3. amphiphilic - 'both loving'
108
What are the characteristics of a lyophobic colloid?
- particles and dispersant have different characteristics therefore
- minimal attraction for dispersant from particles
- thermodynamically unstable system; particles aggregate to lower their surface energy
- require careful formulation
109
what are some examples of lyophobic colloids?
- water insoluble drugs
- clays, oils
110
What are the characteristics of a lyophilic colloid system?
- particles have affinity for dispersant , therefore
- solvation occurs as particles interact with dispersant
- inherently stable therefore
- more straightforward to formulate
111
what is the word to describe solvation when water is the solvent?
hydration
112
why are lyphophilic colloid systems inherently stable?
solvation forms solvent shells - act as protective coat and prevent coagulation
113
what are some examples of lyophilic colloid systems?
starch, gums e.g. acacia in water
114
What are the characteristics of amphiphilic colloids?
- some molecules have regions with different affinities for continuous phase e.g hydrophobic tails
they will orientate themselves so each part is in contact with preferred phase
- molecules will arrange @ surface until no space left
115
what is the 'critical micelle concentration' ?
the concentration at which there is no surface space left for molecules to arrange themselves
amphiphiles will form spherical structures - micelles - to allow them to remain oriented towards preferred phase
116
What is a liposome?
bilayer-containing structures that some amphiphiles will artange themselves in
- 'pocket' of continuous phase within them (can encapsulate lyophilic materials)
117
How can colloidal systems be utilised?
dissolving of lyophobic drugs in micelle or liposome bilayer to 'solubilise' poorly soluble drugs
118
Why are micelles and liposomes referred to as 'association colloids' ?
they constantly disassociate and reassociate with one another to form new structures
119
What are nanoparticles?
What is an advantage to using nanoparticles?
solid particles between 1-100nm diameter
(can be used as disperse phase in some colloids)
their properties can be tailored to maximise their usefulness e.g.
size, surface structures, shape, material
120
What are the optical properties of colloids?
How does particle size influence their optical properties?
colloidal particles can interfere with path of light travelling through
- scatter light depending on particle size
small particles 'bend' light more than big particles
121
What is the Tyndall Effect?
occurs when shining light through colloidal suspension
scattering of light causes beam path to become illuminated
(individual particles visible in suspensions)
122
What two factors influence the light scattering abilities of colloids?
1. particle size
2. wavelength of light
123
How does light wavelength influence light scattering through a colloid?
short wavelength e.g. violet/blue is scattered MORE than
long wavelength e.g. red
124
How can light scattering be utilised to measure particle size in a disperse system?
1. a laser diffraction particle size analyser shines beam of laser light onto particles in single file
2. detector measures amount of deflection of light
3. size of particle is calculated from amount of deflection
125
Why are larger particles (suspensions) more commonly used in formulations than colloids?
- had to generate small enough particulates for some materials as surface energy may cause clumping
- 'wetting' (solvating) can be hard due to air adsorption at the surface of particles
126
What is the definition of a suspension?
a formulation of insoluble solid particles (over 1 micrometer in size) distributed throughout a liquid continuous phase
127
What sorts of drugs are commonly formulated as oily suspensions (depots) ?
Why?
antipsychotics and steroids e.g. hormones
- remain as oily globules after injection
- reduce SA in contact with body fluids
- slowed absorption rate
128
what is meant by 'wetting' ?
why must it be the first stage of forming suspension?
the ability of a solid particle to stay in contact with a liquid
particles will remain on liquid surface, attach to container or form clumps
129
What are diffusible solids?
easily wetted particles so straightforward to suspend in aqueous phase
130
what are indiffusible solids?
show some hydrophobicity, not easily wetted therefore need wetting agent
131
Why are finely divided substances particularly hard to wet?
due to presence of an adsorbed layer of air around the particles
132
how do wetting agents aid wetting and dispersion?
decrease interfacial tension
133
What is interfacial tension? Why does it exist?
- cohesive forces exist between molecules in each phase
- tend to be larger force
- adhesive forces exist between two different phases
inbalance of forces creates tension at surface
134
What is the degree of wettability determined by?
the difference between the adhesive and cohesive forces
135
What are three types of wetting agent?
1. Surface active agents AKA detergents
2. hydrophilic colloids
3. solvents
136
How do detergents (SAAs) work as wetting agents?
HC chains adsorbed to hydrophobic particle surfaces, polar groups enter liquid and become hydrated
137
Why might they cause excessive foaming?
What else can detergents cause?
due to stabilisation of bubbles created when air is mixed in the system
deflocculation of the system
138
How do hydrophilic colloids work as wetting agents?
give particles hydrophilic character by coating them with a layer
- can be used in combo with detergents
- may also cause deflocculation
139
How do solvents work as wetting agents?
water miscible solvents decrease interfacial tension by penetrating powder clumps and displacing air
140
What is the minimum particle size for which gravity becomes significant in causing sedimentation?
0.5 - 1 micrometer
141
What is Ostwald ripening?
when smaller particles dissolve and redeposit onto larger particles
- potential issue in suspensions with a range of particle sizes
142
What is the process of Otswald ripening e.g. when temp increases, decreases
increase in temp means increase in solubility therefore
- loss of molecules to solution from particle surface
- smaller particles have greater SA:mass therefore lose high proportion
when temp decreases again
molecules want to re-join surface of particle ie. precipitate out
- larger SA on large particles therefore more available space for molecules
143
What is the net effect of an increase then decrease in temperature, due to Otswald ripening?
formation of larger particles, higher proportion of large:small
144
Why are 'insoluble' actives favoured to reduce the likelihood of Otswald ripening?
insoluble actives will have vv low solubility in continuous phase
the lower the solubility the better as less likely to lead to Otswald ripening
145
How can substances with borderline solubility have their solubilities reduced to ensure stability of suspension?
1. antisolvents (opposite of cosolvents)
2. pH
3. drug salts
146
What determines the effect of density upon the sedimentation rate?
How can density be altered?
the density difference between the particles and vehicle (continuous phase)
density modifiers - lessen the difference in density between the two phases
147
What is the definition of viscosity?
What is the physical definition?
the resistance of a fluid to flow/movement
the internal friction of a fluid, produced by intermolecular forces within the liquid phase
148
What five factors can influence viscosity?
with explanation
1. molecular size e.g. larger molecules are more viscous
2. molecular shape e.g. influences area for IMFs, branched chain will act smaller (viscosity wise) than straight chain
3. molecular chemistry e.g. polar molecules form H bonds, increase viscosity due to movement resistance
4. molecular concentration - high conc means more molecule interaction, higher viscosity
5. temperature - increasing temp adds energy, more movement, less viscous
plus can break IMFs
149
what is shearing stress?
force per unit area required to cause a liquid to flow
150
what is the 'rate of shear' ?
the difference in velocity between two planes of liquid a given distance apart
(think of liquid as deck of cards, moving top layer; each layer moves at different speed proportional to its distance from the bottom layer, which is stationary)
151
What did Newton notice in regards to flow?
rate of flow of a liquid is directly proportional to the force applied by the constant viscosity
ie. the higher the viscosity, the greater force per unit area required to produce a given flow rate
152
What is Newtonian flow?
substances that continue to flow in the same way, regardless of the forces acting upon them
ie. when pushed/pulled, they move/change shape in proportion to force applied e.g. water
RARE in pharmaceutical formulations
153
What are non-Newtonian substances?
fluids that do not behave in linear ways,
do not have constant viscosity (changes with applied shear force),
properties change in response to movement
154
What is plastic flow characterised by?
When can it be seen?
minimum force beyond which the material flows (yield stress/value)
in concentrated suspensions with flocculated particles and high viscosity continuous phases
155
What is pseudoplastic flow characterised by?
When can it be seen?
viscosity decreases with the rate of shear AKA shear thinning fluid
seen in flocculated dispersions containing long, high molecular weight molecules
156
What is dilatant flow characterised by?
When can it be seen?
viscosity increases with the rate of shear AKA shear thickening fluid
can be seen in dispersions containing a high conc of small, deflocculated particles
157
How does shear thinning/thickening influence particle alignment?
eqbm - random arrangement
shear thinning - in-plane alignment; easier slipping past eachother
shear thickening - out of plane alignment, aggregation (prevents slipping)
158
What is thixotropy?
What is it characterised by?
reversible, time-dependent change in viscosity, in some non-Newtonian fluids
- particles form loose 3D gel structure @ rest
- shear stress (shaking) disrupts bonds, structure, allows aligning of particles, therefore flow (shear thinning)
- when applied stress stops, down curve is displaced to the left of the up curve indicating reform of gel structure (not immediately)
- shear rate is lower on upward curve than downward
159
What must be considered with regards to rheology when designing pharmaceutics?
manufacturing considerations
- mixing
- passing through machinery
- pouring/packing bottles
patient //
- physical stability
- ease of use e.g. spreading
- safety ie. consistent dosing
160
Why is high viscosity preferable during storage?
(low shear stress during storage)
slows/reduces sedimentation
161
Why is low viscosity preferred during shaking?
(high shear stress during shaking)
to redisperse particles
162
What is 'dynamic viscosity' ?
(for a Newtonian liquid)
the coefficient describing the directly proportional relationship between the rate of flow (shear) and applied force (stress)
163
What is 'kinematic viscosity' ?
relates a liquid's viscosity to it's inertial force
- inertial force is equivalent to density
164
What three ways can viscosity be measured practically?
What sorts of equipment might be used?
1. capillary methods - test how fast the sample flows
using capillary viscometers
2. rotating methods - test how hard it is to stir
using rotating viscometers e.g. concentric cylinder or cone-plate
3. falling methods - test how long it takes something to fall through the sample
using falling ball/sphere viscometers
165
In what three ways can a surface acquire an electrical charge when they come into contact with water?
1. ion dissolution
2. ionisation
3. ion adsorption
166
How does ion dissolution cause a surface to have an electrical charge?
- different ions have different solubilities
e.g. silver iodide (Ag+ I-)
solid silver iodide in water
- Ag+ more soluble, dissolve
- I- left behind therefore
surface has overall negative charge
167
How does ionisation result in an electrical charge on a surface?
if particle made of ionisable molecules they may ionise at surface and particle will acquire surface charge
168
What factors influence whether or not a particle will acquire a surface charge due to ionisation?
- pKa of ionisable groups
- pH of dispersant
when pH above pKa of group, neg charged molecule
when pH lower than pKa, pos charged
169
How does ion adsorption result in the production of an electrical charge at a surface?
by unequal adsorption of ions onto the surface e.g. if more anions (-) adsorb, surface will have net neg charge
170
Why are solid particle surfaces more often neg charged than pos due to ion adsorption?
because cations (+) are generally more hydrated than anions (-) so tend to stay in water phase, leaving anions free to adsorb to surface
171
How does the surface charge of particles in a disperse system influence the distribution of ions in the rest of the liquid?
What is the overall effect of this?
the electrical double layer
uneven distribution of ions in a disperse system
172
What is the electrical double layer?
How can it be split?
layer around each particle with different composition from rest of system
inner region - includes charged surface and adsorbed ions of opposite charge to surface (counterions)
diffuse region - lies beyond adsorbed ions and up to edge of electrically neutral region
contains counterions and co-ions
electrically neutral region - outside edl; bulk continuous phase
uniform distribution of ions
173
What is a difference in charge between two areas called?
a potential
174
How are electrical potentials measured in regards to colloids and suspensions?
What will the highest potential be between?
Potential decreases with what? In what pattern?
measured against electrically neutral region (ENR) ie bulk solution
highest potential between ENR and particle surface
decreases with distance from surface of particle (rapidly and linearly to Stern plane)
then gradual exponential decrease to zero?
175
What is the DeBye Huckel length, 1/k ?
What is k and what does it depend on?
the distance to the electrically neutral region
ie. thickness of electrical double layer, covers exponential region of graph
value varies with system - depends on electrolyte conc of liquid phase
176
How can the thickness of the EDL be decreased?
addition of electrolytes; increases k and decreases 1/k
177
What is the Nernst potential?
the potential difference between the actual surface of the particle and the electroneutral region of the solution
178
What is the Stern potential?
potential between the Stern plane and the ENR
179
What is the zeta potential?
What does it indicate?
potential between the shear plane and the ENR - can be used as measure of forces acting in a system
indicates degree of repulsion between adjacent, similarly charged, dispersed particles
180
Why does a higher zeta potential indicate more stability for a system?
What values indicate stable dispersion system?
As zeta value approaches zero, attractive forces exceed repulsive forces and particles stick together
zeta value >+30 or <-30 mv
181
Why do particles tend to associate when they meet?
to decrease their SA in contact with liquid
182
Why is the balance of attractive and repulsive forces between particles important important for system stability?
decides whether particles rebound and stay separate after collisions or stay permanently attached which could lead to irreversible sedimentation
183
What are attractive interactions, Va?
what is the relationship between attraction and distance?
result from VDW forces between molecules in surface layers of interacting particles
attraction decreases as distance between particles increases
184
What are repulsive interactions, Vr?
result from electrical charges on surface of particles due to
- adsorption of charged polymers or surfactants @ interface
- polarity differences between solid and liquid
- ionisation of chemical groups @ surface of particles
- adsorption of small inorganic ions onto particle surfaces
185
Over what distance do repulsive interactions, Vr, act?
approximate thickness of the EDL
186
What is the relationship between repulsive interactions and distance?
Vr decreases with distance but more sharply than Va
187
What is DVLO theory used to describe?
What is the equation?
The interaction between two particles in terms of vdw attractive forces, Va and electrical repulsive forces Vr
Vt = Va + Vr
Where Vt is the total of the attractive and repulsive forces
188
What is the ‘primary minimum’ on a DVLO graph?
When Va (attractive interactions) dominate at very low inter particulate distance (particles close together)
189
What is the primary maximum on a DVLO graph?
What two factors does it’s height depend on?
Occurs at intermediate distances (within thickness of EDL)
- Vr
- surface and zeta potential
190
What is the secondary minimum on a DVLO graph?
What does the depth depend on?
The trough - occurs at v large H value because even though Va decreases with distance, Vr decreases more sharply
Depth depends on particle size
191
What are three types of aggregation?
Are they reversible?
1. Coagulation/full flocculation - irreversible
2. Deflocculation (becoming non-aggregated)
3. Partial flocculation - reversible
192
At what point of a DVLO graph does coagulation occur?
What is formed? How?
Is it possible to redisperse?
The primary minimum
particles settle quickly and are closely aggregated - forms single large aggregate
Difficult or impossible
193
At what point on a DVLO graph does deflocculation occur?
What is happening to the particles?
Why are the particles able to slide past each other as they sediment?
Are the particles redispersable upon shaking?
At primary maximum
Particles remain separate (are small), settle slowly
Vr
Not easily
194
At what point on a DVLO graph does (partial) flocculation occur?
What does flocculation involve?
Why is sedimentation rapid?
At secondary minimum
Formation of loose aggregates of particles which constantly break up and reform
Aggregates are relatively large
195
Why is the sedimentation volume high during flocculation?
How can a homogeneous system be obtained?
Liquid is trapped within and between aggregates
Shaking - can re-disperse the sediment
196
What happens to flocculated particles upon storage?
They become clayed
197
What happens to deflocculated particles upon storage?
They become caked
198
How does distance between particles differ between flocculated and deflocculated material?
Flocculated - clumped particles
Deflocculated - separate particles
199
How does speed of particle settling differ between flocculated and deflocculated materials?
Flocculated - quickly
Deflocculated - slowly
200
How does vehicle trapping differ between flocculated and deflocculated materials?
Flocculated - vehicle is trapped
Deflocculated - vehicle is not trapped
201
How does the appearance of the liquid differ between settled flocculated and deflocculated materials and what do they become?
Flocculated - clayed - clear liquid
Defloccculated - caked - turbid
202
How does sediment packing differ between clayed (flocculated) and caked (deflocculated) materials?
Clayed - loosely packed
Caked - densely packed
203
In clayed and caked sediments, which forces dominate?
Clayed - attractive forces
Caked - repulsive forces
204
Why are pharmaceutical calculations often designed as flocculated instead of de-flocculated?
- easy to re-disperse
- can increase viscosity using modifiers to minimise sedimentation but so it still remains pourable
205
In what three ways can suspensions and colloids be stabilised?
1. Altering zeta potential
2. Bridging agents
3. Steric stabilisation
206
What two factors can be manipulated to change zeta potential?
Electrolyte conc and pH
207
What is the result of adding an electrolyte with the opposite charge of the particle surface?
- electrolyte will associate with the particle
- Vr will decrease, so will zeta potential
Particles will therefore repel less and flocculation can occur
208
How does the amount of electrolyte added alter the degree of flocculation (assuming the electrolyte is oppositely charged to the particles) ?
Small amount - flocculation
Large amount - coagulation
Very large amounts - charge reversal - deflocculation
209
What does the Schultz-Hardy rule show?
Ability of an electrolyte to flocculate particles depends on its valency
Trivalent > divalent > monovalent
210
What two sorts of bridging agents are there?
What can charged SAAs act in combo with?
Non-ionic surface active agents (SAAs) and hydrophilic polymers ie. Long chain branched molecules
Electrolytes
211
How do Surface Active Agents (SAAs) work as bridging agents?
Can adsorb onto more than one particle at once to form bridge and therefore loose flocculated structures
212
How do hydrophilic polymers work as bridging agents?
What does it form?
Part of chain adsorbs onto a particle and the rest bridges to other particles
Forms gel-like network, flocculates system
213
How does steric stabilisation work? What is involved?
Non-ionic polymers can adsorb onto particle surface,
Polymer chain keeps particles apart due to repulsive steric interaction
214
How can suspension stability be assessed?
1. Rate of sedimentation
2. Final volume or height of sediment
3. Ease of redispersion
4. Particle size distribution
215
Why is accelerated stability testing used? Is there a disadvantage?
What two methods are there?
Shortens time of some experiments but not always possible to accurately predict normal behaviour from results
1. Centrifugation
2. Temperature cycling
216
What are the disadvantages to using Centrifugation to assess suspension stability?
1. Increases sedimentation rate by increasing acceleration due to gravity
2. May destroy structure of flocculated system by forming tightly packed sediment (may not have occurred under normal conditions)
217
What is the disadvantage to using temperature cycling as a stability test for suspensions?
Moving between extremes of temp - ie. 40 degrees and zero - increases rate of degradation, esp crystal growth
218
Why do we use sedimentation volume, F?
Plots of F vs time allow comparisons between formulations
219
For a graph of F/time, what does it mean when F plateaus?
Sedimentation is complete
220
For a plot of F/time, what does it mean when F = 1?
1. Volume of sediment = original volume of suspension
2. No clear supernatant is seen on standing
3. Product is in ‘flocculation equilibrium’
221
What is a desirable value for sedimentation volume, F, for a pharmaceutical?
F = 1
222
F is usually < 1 but under what circumstances can F be > 1?
If the flocs in a system are loose and fluffy
223
What is the value beta, for degree of flocculation?
Relates volume of flocculated sediment to that in a deflocculated system
(More useful than F)
224
What can the ‘pocket’ of continuous phase within a liposome be used for?
What other feature of a liposome makes them good for drug delivery?
To encapsulate lyophilic materials to control delivery, protect the, from enzymatic degradation when coming into contact with physiological fluids etc
Lipid bilayer is able to fuse with cell membranes to deliver drugs
225
What would be the consequence if a drug was too small to fit a cavity in a cyclodextrin?
Drug will not interact enough with the cyclodextrin and will not be transported
226
What would be the consequence if the association constant between a drug and the cyclodextrin was too high?
Drug would not be delivered to target site as it would not be released from cyclodextrin
227
What would be the consequence of the association constant between a drug and the cyclodextrin being too low?
The drug will not enter the pore and solubility will not be improved
