Science of Medicines Week 27 Flashcards
1
Q
define emulsion
A
disperse systems in which an insoluble liquid is dispersed in a second liquid phase
2
Q
define disperse phase (internal phase)
A
the liquid phase that is broken into tiny droplets and dispersed through the system
3
Q
define continuous phase (external phase)
A
the phase in which the disperse phase is distributed
4
Q
What are examples of uses of emulsions in pharmacy?
A
cream formulations, parenteral nutrition, oral administration, rectal administration of anti-epileptic agents
5
Q
What are the 2 main types of emulsion?
A
oil-in-water and water-in-oil
6
Q
define oil-in-water emulsion
A
the oil is the disperse phase and water is the continuous phase
7
Q
define water-in-oil emulsion
A
the water is the disperse phase and oil is the continuous phase
8
Q
What are the advantages of emulsions?
A
- delivery of drugs with low aqueous solubility
- taste masking
- oils with therapeutic effects
- avoids irritation of mucosa as drug is dissolved in the internal phase
- patients may have difficulty swallowing tablets
- total parenteral nutrition
9
Q
What are the disadvantages of emulsions?
A
- unstable - need to ensure the two phases do not separate
- may be hard to manufacture due to this
10
Q
What is the 3rd type of emulsion?
A
multiple emulsion (w/o/w)
emulsions in which the disperse phase contains droplets of another phase
11
Q
What are the features of acceptable pharmaceutical emulsions?
A
- physical stability!
- flow properties
- ideal viscosity (think creams)
- aesthetically pleasing
- suitable flavour
- correct texture
12
Q
What are the 3 components of an emulsion?
A
water, oil and an emulsifying agent
13
Q
What is the emulsion type determined by?
A
the stability of the disperse phase - the less stable phase merges, forming the continuous phase
14
Q
What are the 3 main factors that determine the type of emulsion produced?
A
- the phase volume of the internal phase
- the chemical properties of the emulsifying agent surrounding the internal phase
- the viscosity of the internal and external phases
15
Q
How does the phase volume of the internal phase determine the emulsion produced?
A
- the dispersed phase (internal phase) must be less than 50% of the total volume for stability
- if the dispersed phase exceeds 50%, phase inversion may occur and the system becomes unstable
16
Q
How do the chemical properties of the emulsifying agent determine the emulsion formed?
A
- the emulsifying agent forms a protective film around the disperse phase
- hydrophilic emulsifiers favour O/W emulsions
- lipophilic emulsifiers favour W/O emulsions
17
Q
How does the viscosity of the phases determine the emulsion formed?
A
- a higher viscosity in the external phase slows down droplet movement, reducing merging and increasing stability
- a lower viscosity of the external phase compared to the internal phase means droplets move freely, increasing the chance of merging and reducing stability
18
Q
What are the 3 different tests for identifying emulsion types?
A
- miscibility testing
- staining tests by incorporation of an oil-soluble dye
- conductivity tests
19
Q
How do you use miscibility tests to test for emulsion types?
A
O/W = are miscible with water but not oil
W/O = are miscible with oil but not water
20
Q
How do you use staining tests by incorporation of an oil-soluble dye to test for emulsion types?
A
O/W = macroscopic shows a paler colour than W/O (dye goes into droplets, so continuous phase has less colour)
microscopic shows coloured dots on a colourless background
W/O = macroscopic shows a more intense colour as dye goes into continuous phase
microscopic shows colourless dots against a coloured background
21
Q
How do you use conductivity tests to test for emulsion types?
A
O/W = conducts electricity
W/O = does not conduct, the lamp in the circuit will only flicker or not glow at all
22
Q
What are the 4 emulsion instability issues?
A
- flocculation
- creaming
- breaking or cracking
- coalescence
23
Q
define cracking (breaking)
A
the complete merging of the internal phase, resulting in the separation of the emulsion into two layers
24
Q
Is cracking reversible or irreversible?
A
irreversible - emulsion cannot be recovered by shaking
25
What is cracking caused by?
the destruction of the emulsifying agent at the interface between the disperse and continuous phase
26
What are reasons why cracking may occur?
1. incorrect emulsifying agent used
2. incompatible excipients
3. temperature
4. microbial spoilage
27
What is flocculation?
where droplets of the disperse phase loosely aggregate together
28
Why does flocculation occur?
secondary interactions (VDW) forces keep droplets at a defined distance of separation within the secondary minimum
29
Is flocculation reversible?
yes, with shaking
30
What is coalescence?
when droplets of the disperse phase merge together to form larger droplets
31
define creaming
an unstable state caused by a density difference between the oil and water phases and involves either sedimentation or elevation of droplets of the dispersed phase
32
Can creaming be reversed?
yes with shaking
33
Which equation is creaming given by?
Stokes equation - essentially the same as sedimentation in suspensions
34
Which factors reduce the rate of creaming?
decreasing the average particle size of the disperse phase and increasing the viscosity of the emulsion
35
define phase inversion
switching of an o/w emulsion to a w/o emulsion or vice versa
36
When does phase inversion occur?
when the critical value of the phase volume ratio has been exceeded - ideally should be 50/50
37
What is the critical volume ratio for an O/W emulsion?
74:26
38
What is the critical volume ratio for a W/O emulsion?
40:60
39
What do hydrophilic polymers do in emulsions?
they adsorb at the interface between the disperse and continuous phase
40
What are adsorbed particles added into suspensions for?
they are finely divided solid particles that are sufficiently wetted by both phases of the emulsion - so stabilise them
41
If adsorbed particles are preferably wetted by the aqueous phase, which emulsion forms?
O/W emulsion
42
If adsorbed particles are preferably wetted by the oil phase, which emulsion forms?
W/O emulsion
43
What are examples of adsorbed particles used for O/W emulsions?
aluminium hydroxide, magnesium hydroxide, bentonite, kaolin
44
What are examples of adsorbed particles used for W/O emulsions?
talc, black carbon
45
Which 3 main factors need to be considered when formulating an emulsion?
1. the volume of the disperse phase
2. droplet size
3. the viscosity of the internal and external phases
46
Why must we consider the volume of the disperse phase?
if the volume of the disperse phase is too high, it may cause merging of droplets, causing phase inversion
47
Why must we consider the droplet size in emulsions?
decreasing the droplet size by colloid milling increases the stability of the emulsion by reducing the rate of creaming
48
Why must we consider the viscosity of the internal and external phases?
increasing viscosity of both phases helps to stabilise the emulsion by reducing the rate of creaming
49
Which 2 factors does the emulsifying agent used determine?
1. the type of emulsion
2. the clinical use and toxicity
50
For an O/W emulsion, which type of emulsifier is needed for the internal phase?
a hydrophilic emulsifier - higher HLB
51
For an W/O emulsion, which type of emulsifier is needed for the internal phase?
a lipophilic emulsifier - lower HLB
52
How do emulsifying agents work?
in an O/W emulsion, the hydrophilic part of the emulsifier is attracted to the water phase, allowing it to stabilise the oil droplets in the disperse phase and form a protective layer around them, preventing the, from coalescing (merging together)
53
Why are HLB requirements of the internal phase so important?
they help determine which emulsifiers can be used and in what proportions to get the required emulsion type
54
What is the equation for working out a HLB proportion mix?
For example, span 60 (4.7) and tween 80 (15), want HLB of 10
HLB = (weight of A x HLB of A) + (weight of B x HLB of B)
10 = 4.7x + (1-x) x 15
55
What happens if you combine a very low and high HLB surfactant?
you may end up with instability or improper emulsification as the surfactants may not properly balance either phase
56
What are the 4 main types of surfactants used in emulsions?
1. natural source
2. anionic emulsifying wax
3. non-ionic emulsifying wax
4. beeswax
57
What is the vehicle used for the aqueous phase in emulsions?
purified water - we also need buffers to control pH
58
What is the vehicle used for the oil phase in emulsions?
vegetable oils such as cottonseed oil, almond oil
59
What is needed after dissolution of both phases when manufacturing an emulsion?
turbulent mixing conditions - at a lab scale, it is done by a stirrer and in production-scale batches, done by mechanical stirrers, homogenisers, colloid mills and ultrasonifers
60
What are the reasons we do not administer pure drugs?
1. dose
2. taste
3. physical properties - excipients control solubility, bioavailability etc
4. control rate of absorption
5. administration via specific routes
6. handling, transport and marketing
61
What is the difference between Panadol and Panadol actifast?
Panadol actifast has the exact same ingredients BUT also sodium carbonate which is a super-disintegrant to increase rate of dissolution
62
What does sodium carbonate in effervescent tablets do?
increases the rate of integration, dissolution and gastric emptying - faster rate of absorption and drug onset
63
define excipient
all the other components of a formulation other than the API
64
What properties must an excipient have?
1. chemically and physiologically inert
2. meet the moral or religious requirements of some patients
65
What are the 4 main uses for excipients?
1. aid processing during manufacturing
2. protect and support the bioavailability, stability of the drug
3. help in product identification
4. enhance the overall safety and effectiveness of the drug product during storage and use
66
define diluent
inert substances which are added to the API to make a reasonable sized tablet
67
What is the most common diluent?
lactose - it has a good taste, quickly dissolves in water and is not hygroscopic
68
What is the issue with using starches as diluents?
they are very hygroscopic with over 14% moisture
69
What is an example of a very popular compression diluent?
microcrystalline cellulose (MCC)
70
What are the benefits of microcrystalline cellulose?
- good compressability
- gives good tablet strength from low compression forces
- some lubricant and disintegrating properties
71
What is the issue with using microcrystalline cellulose?
- it is sensitive to lubricant, and lubricants hinder the strong bonds forming between the layer of microcrystalline cellulose weakening the tablet
- also slightly hygroscopic
72
define lubricant
a substance required to prevent adherence of the tablet to punches and dies and ensure the smooth ejection of the tablet from the die
73
What are the 2 most effective punch lubricants?
talc and magnesium stearate
74
What is the most effective die lubricant?
stearic acid
75
What are the benefits of magnesium stearate as a lubricant?
a thin layer around the granules is just as effective as a thick layer - so only need around 1% w/w
76
What are the disadvantages of magnesium stearate as a lubricant?
- additional processing steps needed to add it into the tablet
- an increased concentration decrease tablet disintegration time as it is hydrophobic
- it reduces wetting of the tablet
- it is incompatible with many drugs, for example it reacts with aspirin's API
77
define glidant
materials added to tablet formulations to improve the flow properties of the granules
78
How do flow agents work?
they reduce the friction between particles and help powders flow more smoothly during manufacturing
79
What is the most commonly used glidant?
fumed silica - a synthetic amorphous colloidal silicon dioxide
80
define disintegrant
a substance ALWAYS needed in tablets to promote the breakdown of tablets in vivo
81
What are 4 examples of mechanisms of tablet disintegration? (don't need to remember)
1. swelling
2. porosity and capillary action
3. deformation
4. gas production
82
What is the most common distintegrant?
starch - others include polyvinylpyrrolidone (PVP), modified starches and celluloses
83
How do super-disintegrants work?
they SWELL when absorbing water, helping the tablet to break apart
84
What is the benefit of using modified starch as a disintegrant?
it has rapid swelling without becoming gel-like and is more effective in lower concentration, so less bulk is added to the tablet
85
define binding agent
a substance that binds powders together in the wet granulation process or granules during direct compression
86
In which 2 ways can binding agents be added?
1. as a powder into the formulation
2. as a solution to the mixed powders in wet granulation
87
What is the main issue with binding agents?
they may affect the dissolution rate
88
What is the most important binding agent?
polyvinylpyrrolidone (PVP) - it is soluble in water and alcohol and allows rapid release of the drug
89
define adsorbent
a substance which can hold quantities of fluids in an apparently dry state
90
What are examples of tablet ingredients that can be mixed with adsorbents when formulating a tablet?
liquid flavourings, fluid extracts, oils
91
What are commonly used adsorbents?
fumed silica, microcrystalline cellulose, kaolin, magnesium carbonate
92
