Medicinal Emulsions

Question 1

Tutorial on Emulsions
1. Consider the following formulation for a topical cream:
Component Amount (%w/v) Required HLB
Glyceryl Stearate 5 3.8
Cetyl Alcohol 5 15.0
Liquid Paraffin 40 12.0
Surfactants 10 -
Distilled Water to 100 mL
(a) Calculate the Total Required HLB for the non-aqueous components.

Answer 1

Glyceryl Stearate = 5/50 x 3.8 = 0.38
Cetyl Alcohol = 5/50 x 15.0 = 1.50
Liquid Paraffin = 40/50 x 12.0 = 9.60
Total RHLB = 0.38 + 1.50 + 9.60 = 11.48

Question 2

Tutorial on Emulsions
1. Consider the following formulation for a topical cream:
Component Amount (%w/v) Required HLB
Glyceryl Stearate 5 3.8
Cetyl Alcohol 5 15.0
Liquid Paraffin 40 12.0
Surfactants 10 -
Distilled Water to 100 mL
(b) Calculate the relative amounts of Tween 80 (HLB = 15.0) and Span
60 (HLB = 4.7) required to produce a stable emulsion.

Answer 2

Fraction of Tween 80 = (11.48 – 4.7)/(15.0 – 4.7) = 0.66
Fraction of Span 60 = 1.00 – 0.66 = 0.34
For 10 g of surfactants ⇒ 6.6 g of Tween 80
3.4 g of Span 60

Question 3

2. Draw the chemical structure of glycerol monostearate and state the type of emulsifying agent (surfactant).

Answer 3

Non-ionic EA. Monosubstituted ester of glycerol and stearic acid.

Question 4

What is an emulsion?

Answer 4

Liquid formulations for internal application, Composed of two phases consisting of fine
droplets of oil or water (0.1 – 100 mm) dispersed
in water or oil.
emulsions for external application are normally
referred to as lotions, applications or liniments.
‘Semi-solids’ are commonly known as ‘creams’
Oral emulsions are almost exclusively oil in water.

Question 5

What is Oil in Water?

Answer 5

Oil in Water (O/W)
Oil is the disperse phase.
Water is the continuous phase
Used in invariability for oral and IV medicines

Question 6

What is water in Oil?

Answer 6

Water in oil (W/O)
Water is the disperse phase
Oil is the continuous phase
* Mainly external uses as emollients (‘greasy bases’)
although can be used as IM or ‘depot’ injections.

Question 7

What ARE Multiple Emulsions?

Answer 7

Multiple emulsions (O/W/O or W/O/W)
Oil droplet enclosing a water droplet suspended in water!
Water droplet enclosing an oil droplet suspended in oil!
* Have uses as delayed action delivery systems.

Question 8

What are microemulsions?

Answer 8

When the dispersed droplets are 1 nm – 1 mm in size, the formulation is referred to as a ‘microemulsion’.
These systems have many similarities to colloids
and are sometimes termed ‘colloidal emulsions’.
They are homogeneous, transparent systems that are (generally) thermodynamically stable.
Contain more than one surfactant
Typically O/W or W/O, they are 10-200 nm in size
and constitute form 20-80% of the total volume.
Have been used as IV delivery systems but are more
commonly used as topical delivery systems.

They are thermodynamically stable

Question 9

How do you determine O/W or W/O

Answer 9

Use of hydrophilic/hydrophobic (lipophilic/lipophobic) dyes

Conductivity Test - O/W conducts electricity much better than W/O

Miscibility in Oil or Water?
Better in Oil is W/O Better in water is O/W

Question 10

What is interfacial tension? What does it allow?

Answer 10

Boundary between two phases is termed the interface

Interfacial tension causes both phases to remain seperate

Total energy contained within interfacial tension is dependent on the surface area in contact with the other phase.

the cohesive force between the molecules of seperate liquids is greater than the adhesive force between the two liquids

Question 11

What is the disperse phase? What is the interfacial tension between the droplets low or high? and why?
Finally what happens?

Answer 11

The phase that remains in droplet form the longest
should become the disperse phase. As interfacial tension between droplets is high,
(exacerbated by the extremely high surface area)
droplets quickly coalesce to lower the tension.

Complete phase separation eventually occurs.

Question 12

What emulsion is used for fatty or oily medications or for oil soluble drugs?

Answer 12

O/W emulsions

Question 13

What is used to mask taste in medications, what emulsion are they?

Answer 13

Water soluble flavouring (sugar) will mask any unpleasant taste ( for liquid paraffin, cod-liver oil or caster oil)

Question 14

What are the most common emulsifying agents in oral preparations?

Answer 14

Synthetic non-ionic surfactants (polyoxyethylene sorbitan esters) hydrocolloids (acacia, tragacanth) and gelatine are commonly used as emulsifying agents in oral preparations.

Question 15

What is TPN and what emulsion is used?

Answer 15

These emulsions are formulated for IV injection to patients who are unable to feed orally. This is known as Total Parenteral Nutrition (TPN).

Question 16

What ingrediants are used in TPN and why?

Answer 16

Cottonseed, olive, soya bean and safflower are natural oils with high calorific values used in TPN.

Question 17

What emulsion are IV and how does work?

Answer 17

Invariably O/W. The disperse phase (oil phase) will solubilise many lipophilic vitamins and proteins which are present naturally in the oils.

Question 18

Disadvantage of emulsifiers in IV? and example of brands?

Answer 18

However, emulsifyers for TPN are limited in number due to toxicity concerns but lecithin (phospholipids found in plant and animal tissues, eg egg-yolk) are commonly used.

Intralipid™, Lipofunden™, Structolipid™, ClinOleic™ etc. (*see British National Formulary, BNF)

Question 19

What emuslions do you get for topical uses? and examples?

Answer 19

O/W creams and lotions can be applied evenly to the skin and are fully washable (contain ‘macrogols’ eg Carbowax™).

W/O creams (‘ointments’) are ‘greasy’ in texture and can be made to act as barriers to aqueous solutions (occlusive).

The most commonly used ointment bases consist of
soft paraffin or a combination of soft, liquid and hard paraffin.

Question 20

What emuslions do you get for topical uses? and examples?

Answer 20

O/W creams and lotions can be applied evenly to the skin and are fully washable (contain ‘macrogols’ eg Carbowax™).

W/O creams (‘ointments’) are ‘greasy’ in texture and can be made to act as barriers to aqueous solutions (occlusive).

The most commonly used ointment bases consist of
soft paraffin or a combination of soft, liquid and hard paraffin.

Question 21

What is the most common emulsion used as a drug carrier?

Answer 21

For diseases of the skin, emulsions are used as drug carriers.
Generally, only a superficial drug action is required and undue penetration of the skin may need to be avoided, eg corticosteroid creams such as Dermacort™.

Question 22

What does HLB mean?

Answer 22

An HLB number is assigned to the emulsifying agent,
This is characteristic of its relative polarity.
The higher the HLB value, the more hydrophilic
the emulsifying agent.
The lower the HLB of an agent, the more hydrophobic the emulsifying agent

Sorbitan esters (Spans™) are lipophilic hence low HLB values (value 0 to 9 tend to be lipophilic)

0-3 antifoaming agents 3-9 W/O emulsifying agents
7-9 tend to be wetting and spreading agents

Poly(oxyethylene) derivatives of the Spans™ (Tweens™) are hydrophilic hence high HLB values.
(12-18 tend to be hydrophillic)

9-12 O/W emulsifying agents 14-16 tend to be detergents

Question 23

Calculation of HLB

Answer 23

% of surfactant RHLB - HLB low
(with higher HLB) = HLB high - HLB low

1. Calculate the overall RHLB of the emulsion
   based on the weight fraction of each oil component, ie multiply each RHLB by the weight fraction.
2. Choose two emulsifying agents with HLBs
   above and below the required HLB of the emulsion.

Question 24

What is the perfect Emulsion?

Answer 24

Globules of disperse phase retain their initial character, ie size and shape ( stability of interface)

Globules remain evenly distributed, ie do not coalesce ( flocculate/deflocculate) do not sediment or cream.

Emulsions do not support bacterial growth.

-  polymers such as proteins and non-ionic surfactants  are effective ‘food’ for bacteria. 

-Produces stable emulsions at low temperatures
- no creaming,
- no cracking,
- no flocculation,
- no deflocculation,
- no phase inversion.
- Non-toxic
- Non-irritant - to stomach (orals)
- to skin (topicals).
- Tasteless - no requirement for taste-masking.
- Odourless - helps to increase compliance.
- Colourless - aesthetics are important.

Question 25

How do you evaluate the stability of emulsions?

Answer 25

• Macroscopic examination

Degree of creaming = Volume of cream or sediment/total volume

• Microscopic examination
  Measure the globule (micelle) size using an optical microscope,
  Coulter counter (electronic particle device),
  laser diffraction (Malvern Zetamaster™/ Mastersizer™ / Ultrasizer™
• Accelerated Stability
  Storage at adverse temperatures (high or low).
  Centrifugation at 200-300 rpm (increase sedimentation).

Question 26

What flow do most emulsiosn exhibit?

Answer 26

Most emulsions (except dilute ones) exhibit
non-Newtonian flow.

However water, olive oil and caster oil are all newtonian (straight through origin)

Question 27

What bacteria degrades liquid paraffin?

Answer 27

Penicillin

Question 28

Where does bacteria usually grow in emulsions?

Answer 28

Aqueous phase

Question 29

What features must the preservative have for emulsions? Give examples of preservatives used in emulsions

Answer 29

Preservative must be un-ionised to be effective at
penetrating the bacterial membrane.
Preservative must not bind to other emulsion
components.
Only free and unbound preservative is effective.

Benzoic acid, p-hydroxybenzoic acid esters,
chloroform, chlorocresol, phenoxyethanol,
quaternary ammonium compounds, organic mercurial compounds.
(eg Thiomersal BP)

Question 30

Desirable properties of preservatives

Answer 30

low toxicity
Bactericidal rather than bacteristatic
Wide anti-bacterial spectrum
Activity not affected by emulsion ingredients
Suitable Partitioning

Question 31

What is the bancroft rule?

Answer 31

Bancroft Rule - The net solubility of an emulsifying agent and oil or water will determine the nature of the emulsion. If the emulsifying agent is more lipophilic or oil soluble then a water and oil emulsion will form where oil forms the continous phase. If the emulsifying agent is more hydrophilic or water soluble then an oil and water emulsion (water is continuous phase)

Question 32

What is adhesion?

Answer 32

In chemistry, “adhesion” refers to the tendency of some substances to cling to other substances. The term comes from the root words “ad” for “other” and “hesion” for “to stick to.” Adhesion is usually caused by interactions between the molecules of the two substances.

Question 33

What is an emulsifying agent?

Answer 33

To prevent breaking of emulsions, a small amount of third substance called an emulsifying agent or emulsifier is added to the emulsion during its preparation. Usually, soaps, detergents, long chain sulphonic acids, lyophilic colloids, alkyl sulphates etc. are used as emulsifying agents.

Question 34

Without a viscocity enhancement what viscocity flow do TWEEN AND SPAN SHOW?

Answer 34

Pseudoplastic flow due to the non newtonian nature of the non ionic emulsifying agent. The viscocuty of an emulsion containing these emulsifying agents will increase with an inc in emulsifying agents.

Question 35

What flow is observed when the dispersed phase is highly fatty or oily? When does inversion occur?

Answer 35

Plastic flow can be observed where emuslsions have high fatty/ oily components in diseresed phase. If dispersed phase recahes 70% phase inversion can occur.

Question 36

If there is a decrease of viscosity what usually has happened?

Answer 36

Decrease of viscosity is often indicative of bacterial contamination because the polysaccharide viscosity enhancers are eaten by the microbes.

Question 37

Example of an ionic emulsifying agent

Answer 37

Sodium stearate (soap) anionic
Cetyltrimethylamonium bromide (cetrimide) cationic

Question 38

Example of non ionic emulsifying agent

Answer 38

Glycerol monostearate