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Emulsion Principles & Oral Emulsions Flashcards

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1
Q

What is an emulsion

A

A liquid or semisolid preparation consisting of TWO immiscible liquids (oil and water) where one of the liquids (disperse phase) is uniformly distributed as spherical droplets (minimum surface area per unit volume) throughout the other (continuous phase). They appear opaque

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2
Q

What is O/W

A

oil droplets dispersed in aqueous continuous phase

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3
Q

What is W/O?

A

water droplets dispersed in oily continuous phase

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4
Q

What are Multiple emulsions

A

created by the second emulsification of an existing emulsion

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5
Q

What are Nanoemulsions?

A

Emulsions with droplets are in colloidal size range – translucent or transparent

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6
Q

What are Microemulsions?

A

swollen micellar phase. They form spontaneously and are thermodynamically stable.

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7
Q

What emulsions range from?

A

low viscosity liquids, to semi-solids

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8
Q

What emulsions can be used for?

A

Oral (always o/w), parenteral or external use (depending on formulation)

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9
Q

What can Parenteral emulsions?

A

used to deliver calories, as carriers for oilsoluble drugs. Can be macro or nano-emulsions.

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10
Q

What is Semi-solid emulsions used for

A

External use – creams

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11
Q

What is viscosity of emulsions determined by?

A

determined by phase volume ratio and the phase in which components solidify and the structure it develops.

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12
Q

O/W vs W/O: What are Oral emulsions

A

O/W

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13
Q

O/W vs W/O: What are Topical emulsions

A

O/W or W/O

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14
Q

How is O/W is often more appealing to patients

A 
- Rubs into skin easily
 Can be removed by washing
 Doesn’t stain clothing
 Evaporation of aqueous continuous phase has cooling effect
 Not occlusive
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15
Q

How is W/O – sometimes classified as ointments

A

 Easily spread on skin
 Oily –> emollient
 More rapid release of oil-soluble medicaments
 Occlusive

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16
Q

What does the type of emulsion formed depends on??

A
  • Method of preparation
  • Phase volume ratio – larger volume phase is usually the continuous
    phase
  • Solubility (or preferential wettability for solids) of emulgent – phase
    in which emulgent is more soluble or wettable will be continuous
    phase
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17
Q

Identification of emulsion type: Miscibility test

A

add small quantity of emulsion to water or oil – will mix only if continuous phase is same as solvent

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18
Q

Identification of emulsion type: Dye Test

A

microscopic examination after staining with oil soluble dye (eg Scarlet Red: W/O -red; O/W – pink) or water soluble dye such as methylene blue

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19
Q

Identification of emulsion type: Conductivity Test

A

O/W will conduct electricity

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20
Q

Why are Emulsions inherently unstable?

A

Emulsions are inherently unstable – shaking oil and water together will result in droplets of one phase developing in the other, but on removal of energy, the droplets will rapidly coalesce and return to 2 phases. The creation of droplets leads to large increase in surface area, so increased surface free energy. ΔG = γΔA

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21
Q

What stabilises the droplets in order to form an emulsion

A

A substance that stabilises the droplets is required in order to form an emulsion – emulsifying agent - forms films at the interface between oil and water

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22
Q

What can kind of film is does an emulsion need?

A

Need a flexible interfacial film that impedes coalescence:
Mixed or single monomolecular film
Multi-molecular film
 Finely divided solids

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23
Q

Film: How does Stabilisation occur

A

film formation and/or rheological stabilisation (increasing viscosity/structure of continuous phase)

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24
Q

What is essential for predicting emulsion stability and incompatibilities

A

A good understanding of the physicochemical nature of the emulsifying agent and the type of emulsion formed is essential

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25
At which concentrations are emulgents required to form interfacial films in o/w creams
o/w creams emulgents are used at concentrations that exceed the amount required to form interfacial films The excess emulgent gives structure to the continuous phase which enhances stability by increasing viscosity (rheological barrier), impeding the approach and coalescence of droplets
26
How can Emulgent systems create structure
Emulgent systems can create structure by forming crystalline hydrates and/or swollen gel phase. Long chain alcohols, used as emulsion stabilisers in creams, (eg cetostearyl alcohol) exist in multiple polymorphic forms. At room temperature α-crystals are responsible for the microstructure of the cream.
27
How is Continuous phase viscoelastic?
Continuous phase is viscoelastic, effectively immobilising the oil droplets --> stabilises the emulsion. The appearance and consistency of the emulsion depends on the components of the structure.
28
Emulsion Instability: What does High surface free energy mean?
Thermodynamically Unstable
29
What form does the Large proportion of the total volume of the disperse phase for max stability?
Very fine droplets
30
Types of Physical Instability
```  Creaming/sedimentation  Flocculation  Ostwald ripening (only with partially miscible components)  Coalescence/cracking  Phase Inversion ```
31
What is Creaming/sedimentation and how is it caused?
Formation of a relatively concentrated emulsion at the surface or bottom of the emulsion Caused by gravity when the disperse phase has different density to the continuous phase. Oil less dense than water, so oil droplets will rise to surface over time. Reverse will happen with W/O emulsion
32
What phenomenon is Creaming/sedimentation
a REVERSIBLE phenomenon. Undesirable – inelegant, precursor to coalescence. - Shaking the emulsion will restore stability
33
Explain the Stoke's Law
Reducing mean droplet size – homogeniser - Maximise proportion of total volume of disperse phase as small droplets Increasing viscosity of continuous phase - Using hydrophilic colloids - Lower temperature storage – but must NOT freeze
34
What is Flocculation
- Clustering of emulsion droplets – attracted to each other but remain separated by continuous phase. DLVO secondary minimum effect (refer to colloids lectures). - Floccules move as a single unit  undesirable due to more rapid creaming. - REVERSIBLE by shaking – supplying enough energy to exceed net attractive forces
35
What is Ostwald Ripening
- Growth of large droplets at the expense of small droplets - Only happens in a system of partially miscible liquids - Extremely small droplets are more soluble than large ones
36
How is Ostwald Ripening IRREVERSIBLE
Different to coalescence as droplets do not need to make contact with one another
37
What is Cracking/coalescence
The merging of droplets to form larger droplets Drainage of the liquid films of continuous phase from between neighbouring droplets as they approach one another. The droplets become distorted and the emulgent film ruptures. Ultimately the phases completely separate - IRREVERSIBLE
38
What is Phase Inversion
When a W/O becomes an O/W emulsion or vice versa. May happen deliberately in preparing an emulsion (eg nanoemulsion) as a result of change in water solubility of non-ionic surfactant with temperature or deliberate alteration of phase volume ratio.
39
Phase Inversion: How does it occur
Phase inversion may occur as an instability if the original phase volume ratio of the emulsion was too high, or when an incompatible agent is added that changes the nature of the emulgent (eg Ca ions change O/W sodium soap to W/O calcium soap)
40
What type of emulsifying agents are imcompatible
Anionic emulsifying agents are usually incompatible with cationic materials (opposite charge) and vice versa. Neutralisation ---> loss of emulgent activity
41
How does precipitation occur in Emulgents?
Emulgents may be precipitated by the addition of materials in which they are insoluble, e.g. hydrophilic colloids by the addition of alcohol.
42
Instability/compatibility: What can the presence of electrolytes result in
- reduce the energy of interaction between adjacent globules - have a salting-out effect (high concentrations of electrolytes can strip emulsifying agents of their hydrated layers and so cause their precipitation). - phase inversion may occur, e.g. addition of divalent metal ion to a sodium soap (O/W) emulsion, will form divalent metal soap, which forms a w/o emulsion. - pH change: Sodium soaps may react with acids to produce the free fatty acid and the sodium salt of the acid. Soapstabilized emulsions are therefore usually formulated at alkaline pH.
43
Interference with interfacial film: O/W + W/O emulgent
incompatible (unless used as stabiliser)
44
Interference with interfacial film: Anionic + cationic
incompatible – loss of surface activity of each; loss of antibacterial effect of QAC
45
Interference with interfacial film: incompatible – dehydration of oxyethylene chains
46
Interference with interfacial film: Soaps (anionic) + acids
incompatible - formation of free fatty acid and loss of surface activity (triethanolamine soaps more stable)
47
Interference with interfacial film: Soaps (anionic) + electrolytes
incompatible – salting out of soap (multivalent soaps more stable)
48
Interference with interfacial film: Monovalent metal/amine soaps (O/W) + di/tri-valent metal ions
incompatible - formation of multivalent metal soaps (W/O) – crack or invert
49
Interference with interfacial film: Ethanol
alters interfacial tension and film
50
What is a useful dosage form for oily medicaments
Oral Emulsions eg liquid paraffin for constipation; oily food supplements/oil-soluble vitamins
51
Oral Emulsions: What is unsuitable to shallow?
Oily substances are unpleasant to swallow – coat inside of mouth, not readily flavoured, potential risk of aspiration pneumonia.
52
Oral Emulsions: How is an O/W emulsion made?
Oil droplets are dispersed in an aqueous phase that can be flavoured. Oil doesn’t come into contact with taste buds, flavoured aqueous phase improves palatability, mouth can be easily cleared of residue by rinsing. Oil soluble sustances in oral emulsion are more quickly absorbed, due to being dissolved in small oil droplets
53
Oral Emulsions: Possible way to incorporate....
otherwise incompatible components (one in oil phase, one in aqueous phase)
54
What are the Disadvantages of Oral emulsions
Effective shaking before use required Stability affected by storage conditions Prone to microbial contamination --> may cause instability
55
Formulation of Oral emulsions: Emulgent
- Emulsifying gum eg acacia | - Methylcellulose, magnesium hydroxide, aluminium hydroxide
56
Formulation of Oral emulsions: Oily phase
- Fixed oils eg castor, cod liver oil, safflower - Mineral oils eg liquid paraffin - Volatile oils eg cinnamon, peppermint oil
57
Formulation of Oral emulsions: Water (aqueous phase)
- Freshly boiled and cooled purified water | - Preservative, flavouring, colouring agents
58
What is susceptible to hydrolysis and microbial attack – preservative required
Acacia: natural polysaccharide – polyvalent colloid – forms multi-molecular barrier at O/W interface
59
Acacia are precipitated by
high concentrations of alcohol and electrolytes – INCOMPATIBILITY
60
What is Acacia suitable for...
Extemporaneous compounding of oral emulsions
61
What is Stable to pH change, but coagulated at high concentrations of electrolytes
Semi-synthetic polymers – Methylcellulose 20 – adsorbs at O/W interface to produce viscoelastic multimolecular layers
62
Semi-synthetic polymers are Suitable for what preparation?
preparation of liquid paraffin emulsions
63
Method of preparation: What is required to reduce droplet size of disperse phase?
Shearing forces E.g. Trituration (in mortar), shaking, homogenisation, electric mixer, sonifier
64
Method of preparation: When preparing in mortar and pestle, What should be prepared first?
a PRIMARY EMULSION should first be prepared
65
Fixed ratio for primary emulsion
- 4: 2: 1 (Oil: Water: Gum) for fixed oils (eg castor oil) - 3: 2: 1 for mineral oils** (liquid paraffin) - 2: 2: 1 for volatile oils (eg peppermint oil)
66
2 different methods for acacia emulsions
- Dry gum method (Continental method) | - Wet gum method (English method)
67
Primary Emulsion: Dry Gum
- Oil measured in DRY measure, correct volume of water measured - Acacia is briefly triturated with oil and then all water is added at once with vigorous trituration - Trituration continues until form very thick, white cream (primary emulsion) in which pestle can stand unaided. Characterised by “clicking” sound. Triturate for 2-3 minutes after formation.
68
Primary Emulsion: Wet Gum
- Oil measured in DRY measure, correct volume of water measured - Acacia triturated with all water to form a smooth mucilage - Oil added in small portions and triturated vigorously and continuously until all added and primary emulsion forms. Continue trituration for 2-3 mins. - If emulsion becomes “ropey” (phase inversion) during preparation, add a little water and triturate until emulsion reforms

Pharmaceutical Formulation (3 decks)

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