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F&T II > Emulsions > Flashcards

Emulsions Flashcards

1
Q

What is the definition of an emulsion?

A
  • An emulsion is a system comprising two immiscible liquid phases, one of which is dispersed as fine globules throughout the other.
  • This system is stabilised by the addition of an emulsifying agent.
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2
Q

What are the components of an emulsion

A

disperse and continuous phase

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3
Q

What are the advantages and limitations of emulsions over other dosage forms?

A

Advantages:

  1. Pharmaceutical emulsions may be used to deliver drugs that are poorly soluble in water but readily soluble in oils and vice versa.
  2. Pharmaceutical emulsions may be used to mask the bitter taste and odour of drugs.
  3. Provide protection to drugs that are susceptible to oxidation or hydrolysis.

Disadvantages:

  1. Pharmaceutical emulsions are thermodynamically stable, process to stabilise them is complex.
  2. Bulky, difficult to transport, and prone to container breakages.
  3. Liable to microbial contamination which can lead to cracking.
  4. Uniform and accurate dose may not be achieved.
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4
Q

What are the different types of emulsions?

A
  1. Simple emulsions
    - o/w emulsion, w/o emulsion
  2. Multiple emulsions
    - w/o/w emulsion, o/w/o emulsion
  3. Microemulsions
    - extremely small globules (10-75nm) dispersed in the continuous phase.
    - appears transparent to the naked eye.
  4. Micellar emulsions
    - relatively high concentration of surfactant and a small proportion of disperse phase which is solubilised by the surfactant.
    - surfactant exists as micelles (5-20nm) which are extremely small, therefore these emulsions appear transparent to the naked eye.

Two types:
- Oil-in-water micellar emulsion
» oil found in the non-polar interior of the micelles, which are present in an aqueous continuous phase.
- Reverse micellar emulsion
» consists of water which is found in the polar interior of the micelles which are present in an oily continuous phase.

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5
Q

What are the different components of an emulsion?

A
  • oil phase
  • emulsifying agents
  • water
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6
Q

What are some characteristics of the oil phase?

A
  • comprise a wide variety of lipids or lipophilic materials (e.g. mineral oils, vegetable oils, silicones and waxes)
  • the following properties of the oil phase are important, affect the performance of the emulsion:
    » Consistency
    » “Feel” or tactile characteristic
    » Stability
    » Drug solubility
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7
Q

What are the different types of emulsifying agents?

A
  • surfactants
  • hydrophilic colloids
  • finely divided solids
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8
Q

What are the factors affecting the selection of emulsifying agents?

A
  • type of emulsion (o/w or w/o)
  • compatibility with other components
  • toxicity of emulsifying agent
  • cost of emulsifying agent
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9
Q

What is the general structure of a surfactant?

A
  • surfactants have a hydrophilic group and lipophilic group in their molecular structure.
  • amphipathic nature causes the molecules to become attached to interfaces, thereby lowering interfacial tension.
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10
Q

What are four major groups of surfactants?

A
  • anionic
  • cationic
  • amphoteric
  • nonionic
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11
Q

What are the properties of anionic surfactants?

A
  • generally employed for external preparations.
  • incompatible with cationic compounds, low pH and high concentration of electrolytes.
  • effectiveness enhanced by nonionic surfactants.
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12
Q

What are the different types of anionic surfactants?

A
  • soaps of monovalent bases
  • soaps of polyvalent bases
  • amine soaps
  • sulphated and sulphonated fatty acids and alcohols
  • quillaia saponins
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13
Q

What are the examples, emulsion type and properties of soaps of monovalent bases?

A

Examples: sodium stearate, potassium stearate, ammonium stearate

Emulsion type: o/w

Properties: presence of polyvalent cations will cause phase inversion.
- sodium and potassium soaps have high pH and are unsuitable for emulsions where a high pH cannot be tolerated.

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14
Q

What are the examples, emulsion type and properties of soaps of polyvalent bases?

A

Examples: calcium oleate, zinc oleate

Emulsion type: w/o

Properties: presence of monovalent cations will cause phase inversion.

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15
Q

What are the examples, emulsion type and properties of amine soaps?

A

Example: triethanolamine stearate

Emulsion type: o/w

Properties: suitable for o/w emulsions where a high pH cannot be tolerated.

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16
Q

What are the examples, emulsion type and properties of sulphated and sulphonated fatty acids and alcohols?

A

Examples: sodium lauryl sulphate, sodium cetyl sulphate

Emulsion type: o/w

Properties: generally more effective than other types but strongly alkaline
SLS + CSA –> Emulsifying Wax

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17
Q

What are the examples and characteristics of cationic surfactants?

A
  • Examples include: quaternary ammonium compounds, such as cetrimide, cetyl pyridinium chloride and benzalkonium chloride.
  • possess emulsifying and antiseptic properties
  • incompatible with anionic compounds
  • promote the formation of o/w compounds.
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18
Q

What are the examples and characteristics of amphoteric surfactants?

A
  • Examples include: lecithin for I/V fat emulsions
  • These surfactants are cationic at low pH and anionic at high pH.
  • Not widely used.
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19
Q

What are the characteristics of nonionic surfactants?

A
  • Low toxicity and irritancy
  • Less sensitive to pH changes and addition of electrolytes
  • For external as well as internal preparations
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20
Q

What are the different types of nonionic surfactants?

A

(1) . Sorbitan esters (SPAN) and polyoxyethylene sorbitan esters (TWEEN)
- blends of sorbitan ester and polyoxyethylene sorbitan ester are usually applied.
- depending on the HLB of the blend, it may promote the formation of o/w or w/o emulsions.

(2) . Glycol and glycerol esters
- e.g. glyceryl monostearate
- promote formation of o/w emulsions
- effectiveness enhanced by soaps of monovalent bases and amine soaps.

(3) . Fatty acid polyglycol esters (POE fatty acid esters)
- e.g. POE(40) stearate
- promote formation of o/w emulsions
- effectiveness enhanced by stearyl alcohol.

(4) . Fatty alcohol polyglycol ethers (POE fatty ethers, macrogol ethers)
- e.g. cetomacrogol 1000
- blends of hydrophilic and lipophilic members are usually employed.
- depending on HLB of the blend, it may promote the formation of o/w or w/o emulsions.
- cetomacrogol 1000 + cetostearyl alcohol –> cetomacrogol emulsifying wax

(5) . Higher fatty acid alcohols
- e.g. cetostearyl alcohol
- auxiliary emulsifying agents

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21
Q

What are the characteristics of hydrophilic colloids?

A
  • These substances are more useful as auxiliary emulsifying agents and as thickening agents.
  • They generally favour the formation of o/w emulsions.
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22
Q

What are the different types of hydrophilic colloids?

A

(1) . Natural and synthetic clays
- e.g. bentonite
- swells in the presence of water but raises the viscosity of the medium only at pH 6 or higher.

(2) . Natural and synthetic gums
- e.g. acacia, tragacanth, sodium alginate
- these are polysaccharides
- they exhibit incompatibility with certain cations or pH.
- sodium alginate and sodium CMC are incompatible with acids,
- methyl cellulose is less soluble in hot water.

(3) . Proteins
- e.g. gelatin, soluble casein
- these are less commonly employed than the gums.
- gelatin is prepared by partial hydrolysis of collagen.

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23
Q

What are the characteristics of finely divide solids?

A
  • solids of mineral origin should be sterilised before use because they may contain tetanus spores.
24
Q

What are the two types of finely divided solids?

A
  1. Polar inorganic solids
    - e.g. heavy metal hydroxides, non-swelling clays
    - favour the formation of o/w emulsions.
  2. Non-polar solids
    - e.g. carbon, glyceryl tristearate
    - favour the formation of w/o emulsions.
25
Q

What is the theory of emulsification?

A

When oil and water are mixed together, droplets of varying sizes are produced. A tension exists at the droplet interface because the two immiscible phases tend to have different attractive forces for a molecule at the interface.

Such a system is thermodynamically unstable.

26
Q

What is the purpose of forming a rigid interfacial film?

A

To contribute to the stability of the emulsion

27
Q

What are the different degrees of tightness of packing of the following complexes?

  1. Cholesterol + sodium cetyl sulphate
  2. Oleyl alcohol + sodium cetyl sulphate
  3. Cetyl alcohol + sodium oleate
A

Cholesterol + sodium cetyl sulphate: closely packed condensed complex

Oleyl alcohol + sodium cetyl sulphate: loosely packed condensed complex

Cetyl alcohol + sodium oleate:
fairly closed packed but no complex formation

28
Q

What does the electric double layer serve as and what does it apply to?

A

Electric barrier serves as an electrical barrier to approach of droplets and applies to ionic surfactants.

29
Q

How to increase the viscosity of the continuous phase and why is it important?

A

Gums and waxes can be used to increase viscosity of water and oil respectively.
A more viscous continuous phase generally produces a more stable emulsion.

30
Q

What is the Bancroft’s theory?

A
  • adsorption of surfactants at the o/w interface gives rise to an interfacial film.
  • film experiences two interfacial tensions, one between the film and the aqueous phase and the other between the film and the oil phase.
    film will curve in the direction of the greater interfacial tension where the disperse phase is on.
31
Q

What is the oriented wedge theory?

A
  • used to explain the type of emulsion formed by soaps
  • surfactant molecules (eg. soaps) will orientate at the oil/water interface such that a tightly packed film is formed.
  • relative location of the polar heads of the soap molecules will determine the type of emulsion produced.
32
Q

How does the oriented wedge theory apply for sodium oleate?

A

comprises one polar head and one non-polar tail, molecules can orientate with their polar heads on the external side of the droplet to allow more molecules to pack at the interface.

33
Q

How does the oriented wedge theory apply for magnesium oleate?

A

comprises one polar head and two non-polar tails, molecules can orientate with their polar heads on the internal side of the droplet to allow more molecules to pack at the interface, resulting in the formation of a w/o emulsion.

34
Q

How does the theory based on angle of contact work?

A
  • applies for emulsifying agents which are finely divided solids with the following properties:
    » insoluble in both aqueous and oily phases
    » preferentially wetted by one of the phases
    » able to form a thin interfacial film
    » of colloidal size
  • solid particles are attracted to the interface between the two immiscible liquids.
  • angle of contact formed by the solid particle at the interface determines type of emulsion produced.
35
Q

How does the HLB concept work?

A
  • a surfactant that consists of a hydrophilic group and a lipophilic group in its molecular structure.
  • ratio of both groups affects the water and the solubility of the surfactant.
  • this ratio is called the hydrophile - lipophile balance.
  • the higher the HLB number, the greater the hydrophilic property and vice versa.
36
Q

How do you calculate HLB?

A

HLB = (weight of hydrophilic group / molecular weight) x 20

  • number 20 represents a molecule which is 100% hydrophilic.
  • HLB number of 15 represents a molecule containing 75% by weight of hydrophilic group.
37
Q

What type of applications fall under the HLB range of:

a) . 4-6
b) . 7-9
c) . 8-18
d) . 13-15
e) . 10-18

A

a) . w/o emulsifying agents
b) . wetting agents
c) . o/w emulsifying agents
d) . detergents
e) . solubilising agents

38
Q

What are the steps for preparing a stable o/w emulsion?

A

1). Calculate the ‘required HLB’ fro the o/w emulsion
2). Select the surfactants and calculate the amounts required
» A blend of surfactants is selected as it is more effective than a single surfactant.
» The blend usually consists of a hydrophilic surfactant and a hydrophobic surfactant.
3). Determine the optimal HLB and surfactant blend

39
Q

How do you decide what is an effective pair of surfactants?

A
  • plot a graph of emulsion stability against HLB of surfactant blend.
  • optimal HLB and calculated HLB should coincide.
40
Q

What are some common additives in the formulation of emulsions?

A

1) . Agent-in-water method
2) . Agent-in-oil method
3) . Nascent soap method
4) . Alternate addition method

41
Q

What is the agent-in-water method?

A
  • Emulsifying agent is incorporated in water and the oil is then added with vigorous agitation, producing o/w emulsion directly.
  • For w/o emulsion, addition of oil is continued until phase inversion occurs.
42
Q

What is the agent-in-oil method?

A
  • Emulsifying agent is incorporated in oil, which is then added to water with vigorous agitation, forming o/w emulsion.
  • For w/o emulsion, the addition of oil phase continues until phase inversion occurs.
43
Q

What is the nascent soap method?

A
  • Suitable for emulsions with soap as the emulsifying agent.
  • Fatty acid is dissolved in the oil and the base in the water.
  • Soap is formed in situ as the oil and aqueous phases come into contact during mixing, and an emulsion is subsequently produced.
  • Depending on the type of soap, o/w or w/o emulsions are produced.
44
Q

What is the alternate addition method?

A
  • This method is particularly suitable for vegetable oils.

- The water and oil are added alternately in small amounts to the emulsifying agent.

45
Q

What are the different types of emulsifying machines?

A
  • simple stirring (e.g. propeller mixer, turbine mixer, paddle mixer)
  • colloid milling
  • vibration and ultrasonification
    » Further homogenization is required to improve stability.
46
Q

What is considered a stable emulsion?

A
  • a stable emulsion has no coalescence of disperse phase, and ultimately leads to the separation of the oil and aqueous phases.
47
Q

What are the signs of emulsion instability?

A

creaming, flocculation, coalescence, cracking

48
Q

How would you describe creaming?

A
  • under the influence of gravity, the globules tend to rise or sediment, depending on the differences in specific gravities between the phases.
  • this results in concentration of the disperse phase at the top or the bottom of the system which can be readily redispersed on shaking.
  • Stokes’ Law gives a better understanding of the creaming process.
49
Q

What is Stokes’ Law and what can it be used to calculate?

A

v = [2r^2 (p1-p2)g] / 9n

  • Stokes’ Law applies to an isolated sphere in an infinitely large mass of liquid.
  • Numerous droplets mutually interfere in an emulsion, and the hindrance to motion depends on the concentration of the droplets of the disperse phase, which in turn depends on the volume fraction of the disperse phase.
  • Velocity of fall or rise of the droplets in an emulsion cannot be calculated directly using Stokes’ Law.
  • Factors expressed in the Stokes’ Law can be used to reduce the rate of creaming and improve the stability of the emulsion.
50
Q

What are the factors expressed in Stokes’ Law that can be used to reduce the rate of creaming and improve the stability of the emulsion?

A
  • radius of droplet
  • viscosity of continuous phase
  • difference in densities of the disperse and continuous phase
51
Q

An ___ in the volume fraction of the ____ phase will ___ the rate of creaming.

A

increase, disperse, reduce

52
Q

How would you describe flocculation?

A
  • reversible aggregation of droplets of the disperse phase.
  • droplets do not lose their identity entirely, mechanical or electrical barrier surrounding the droplet is sufficient to prevent droplet coalescence.
  • aggregates behave as single particles and therefore increase the rate of creaming.
53
Q

How would you describe coalescence?

A
  • droplets joining to form larger drops.

- irreversible process that leads to a decrease in the number of droplets and finally cracking.

54
Q

How would you describe cracking?

A
  • complete breakdown of the emulsion, with coalescence of the droplets and a separation of the two phases into two layers.
  • process is irreversible
  • cracking may result from chemical, physical and biological effects.
  • addition of substances may be incompatible with the emulsifying agent
55
Q

What are some substances that are incompatible with the emulsifying agent and cause cracking of the emulsion?

A
  • strong acids + alkali-metal soaps
  • anionic compounds + cationic surfactants
  • cationic compounds + anionic surfactants
  • high concentration of electrolytes + soaps
  • alcohol + gums
56
Q

What type of stress can the emulsion be subjected to to speed up the stability test?

A
  • centrifugation
  • agitation
  • freeze-thaw cycles
  • heating-cooling cycles
57
Q

What are the different types of stability tests?

A
  1. Determination of degree of separation
    » stable emulsion should not show any separation of phases during its prescribed shelf-life.
  2. Size analysis of globules
    » emulsions which are less stable show greater increase in mean globule size with time.
  3. Determination of electrophoretic property
    » emulsion conductivity is dependent on the degree of dispersion.
    » reduction in conductivity of o/w emulsions indicates oil droplet aggregation and instability.
    » conductivity of o/w emulsion indicates water droplet aggregation and instability.
  4. Determination of viscosity changes
    » emulsion viscosity is affected by globule size and number
    » changes in emulsion viscosity can be used to indicate emulsion stability.

F&T II (15 decks)

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