Medicinal Emulsions

Question 1

What is an emulsion?

Answer 1

Liquid formulations for internal application.
-composed of two phases consisting of fine droplets of oil or water dispersed in oil or water
-oral emulsions are almost exclusively oil in water

-emulsions for external applications are referred to as: lotions, applications, liniments.
-semisolids are reffered to as creams.

Question 2

Oil in water O/W

Answer 2

-Oil is the disperse phase
-water is the continuous phase
-used invariably for oral and IV medicines

Question 3

Water in oil w/o

Answer 3

-water is the disperse phase
-oil is the continuous phase
-mainly external use as emolients although can be used as IM or ‘depot’ injections

Question 4

what is a microemulsions

Answer 4

when the dispersed droplets are smaller than 1nm - 1um in size, the formulation is reffered to as a microemulsion
-these systems have similarities to colloids and are sometimes known as colloidal emulsions

Question 5

characteristics of microemulsions

Answer 5

-dispersed droplets are 1nm- 1um in size
-they are homogenous, transparent systems that are thermodynamically stable
-normally contain more than one surfactant
-typically o/w or w/o, the disperse phase is typically 10-200nm in size and constitutes from 20-80% of the total volume.
-have been used as IV delivery systems but are more commonly used as topical delivery systems

Question 6

what does hydrophobic, hydrophyilic, lipophobic, lipophilic mean?

Answer 6

Hydrophobic - does not like water
hydrophilic - likes water
Lipophilic - fat liking
lipophobic - does not like fat

• Lipophilic is more commonly used as appose to hydrophobe.
  -lipophobic is more commonly used as appose to hydrophilic.

Question 7

How to dermine if a crude emulsion is o/w or w/o

Answer 7

Hydrophilic / hydrophobic dye test
-Hydrophilic dye will colour the water droplets in the emulsion
-hydrophobic dye will colour the oil droplets in the emulsion

-conductivity test - o/w conducts electricity much better than w/o

-miscibility in oil or water
w/o - better in oil

Question 8

How to dermine if a crude emulsion is o/w or w/o

Answer 8

Hydrophilic / hydrophobic dye test
-Hydrophilic dye will colour the water droplets in the emulsion
-hydrophobic dye will colour the oil droplets in the emulsion

-conductivity test - o/w conducts electricity much better than w/o

-miscibility in oil or water
w/o - better in oil
o/w - better in water

Question 9

What is interfacial tension

Answer 9

The reason why oil and water are not miscible in the absense of an emulsifying agent

Question 10

Interfacial tension

Answer 10

-boundary between two phases is termed as the interphase
-interfacial tension causes both phases to remain seperate
-total energy contained wihtin the 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

Stabalisation of emulsions

Answer 11

-when oil and water are mixed both phases initially form droplets
-the phase that remains in droplet form the longest is the dispersed phase
-as interfacial tension between droplets is high, dropletes quickly sperate to lower the tension until complete phase seperation occures.

Question 12

Emulsifying agents

Answer 12

-to maintain the disperse phase as stable dropletes, an emulsifier is added

-effective emulsifiers are surface-active agents (surfactants) that form physical and chemical barriers at the surface of the dispersed droplets lowering the surface tension and maintaining seperation

-hydrophobic (lipophilic) groups in the surfactants favour the oil-phase while hydrophilic (lipophobic) groups favour the aqeous phase.

-electrical or steric repulsion prevents droplets from seperating

Question 13

two main categories of emulsifying agents

Answer 13

Ionic
Non-ionic

Question 14

Ionic EA

Answer 14

• Anionic - Long hydrophobic unsatuturated alkile tale of sodium stearate (soap) has a negatively charged head group (corboxylic group)
• Cationic -Long hydrophobic unsaturated tail of cetrimide has a positively charged head group (Ammonium group)

For oral emulsions ionic surfactants will never be used as they would make the patient violently sick

Question 15

Non-ionic EA

Answer 15

Glyceral monostearte more suitable as oral medicinal surfactant

Question 16

Oral emulsions

Answer 16

almost always o/w
-fats/oils as medcaments or vehicles for oil-soluble drugs are generally pleasent to take as o/w emulsions
-inclusion of a water-soluble flavouring (sugar) will mask any unpleasent taste (eg liquid paraffin, cod liver oil, castor oil)
-fine emulsification may enhance the absorption of lipid-soluble compounds (eg vitamins) assuming an absorbance oil is used. in this case liquid paraffin would be of no use.
-synthetic non-ionic surfactants, hydrocolloids, and gelatine are commonly used as emulsifying agents in oral preperations.

Question 17

Intravenous emulsions

Answer 17

almost always o/w
-these emulsions are formulated for iv injections to patients who are unable to feed orally.
-this is known as total parental nutrition (TPN)
-cottonseed, olive, soya bean, safflower are natural oils safe to use with high clarofiric values
-the disperse phase (oil phase) will solubilise many lipophilic vitamins and proteins which are present naturally in the oils
-emulsifyers for TPN are limited in number due to toxicity concerns but lecithins are commonly used
examples: intralipid, lipofunden, structolipid

Question 18

Topical emulsion

Answer 18

-o/w creams and lotions can be applied evenly to the skin and are fully washable
-w/o creams (ointments) are greasy in texture and can be made to act as barriers to aqeous solutions
-the most commonly used ointment bases consist of paraffin or a combination of soft, liquid and hard paraffin.
-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 be avoided. eg. corticosteroids such as dermacort.

Question 19

Hydrophilic/Lipophilic balance (HLB)

Answer 19

-An HLB number is assigned to the emulsifying agent, this is characterists of its relative polarity.
-The higher the HLB value, the more hydrophilic the EA

-sorbitan esters (spans) are lipophilic hence low HLB values
-poly(oxyethylene) derrivatives of the spans (Tweens) are hydrophilic hence high HLB values

Question 20

hydrophilic and lipophilic favouring

Answer 20

Hydrophilic will favour o/w emulsions
Lipophilic will favour w/o emulsions

Question 21

HLB values

Answer 21

-values that serve as measure of the hydrophilic/lipophilic balance of surfactants

-the higher the HLB of an agent, the more hydrophilic
-the lower the HLB of an agent, the more hydrophobic

Question 22

describe the hlb of spans and tweens

Answer 22

Spans (sorbital esters) are low HLB values - Lipophilic

Tweens (polyoxyethylene derivatives of the spans) are high HLB values - Hydrophilic

Question 23

HLB values scale

Answer 23

Lipophilic
HLB 0-9
w/o emulsifying agents

Hydrophilic
HLB 12-18
o/w emulsifying agents

Question 24

Required HLB (RHLB)

Answer 24

-the oil phase of an o/w emulsion requires a specific HLB
-the oil phase of a w/o emulsion requires a specific HLB

Question 25

Calculation of RHLB

Answer 25

1. Calculate the overall RHLB of the emulsion based on the weight fraction of each component
   - multiply each RHLB by the weight fraction
2. Chose 2 emulsifying agents with HLBs above and below the required HLB of the emulsion

3 . % of surfactant (Higher HLB) = RHLB - HLB low / HLB high - HLB low

Question 26

RHLB calculation continued

Answer 26

Question 27

Ideal emulsion

Answer 27

-globules of disperse phase retain their initial character
ie. size and shape

-globules remain evenly distributed
ie. do not sediment or cream

-emulsions do not support microbial growth
polymers such as proteins and non-ionic surfactants are effective ‘fod’ for bacteria

Question 28

ideal emulsifying agent

Answer 28

-should produce stable emulsions at low temperatures
-no creaming
-no cracking
-no flocculation
-no deflocculation
-no phase inversion

-non toxic
-non irritant - to stomach/skin
-tasteless - no requirement for taste-making
-odourless - increases patient compliance
-colourless - aesthetics are important

Question 29

Macroscopic evaluation

Answer 29

degree of creaming = volume of total cream or sediment / total volume

Question 30

Accelerated stability

Answer 30

storage at adverse temperatures (high or low)
cetrifuation at 200-300rpm (increase sedimentation)

Question 31

Viscosity of emulsions

Answer 31

-the viscosity of emulsions will vary greatly depending on their composition and application
-most emulsions (except dilute ones) exhibit non-newtonian flow

Question 32

visocosity of emulsions - disperse phase

Answer 32

phase-volume ratio - newtonian <0.05
pseudoplastic >0.05
plastic flow&raquo_space;0.05
phase inversion >0.70

-paritcle size decreases as viscosity increases
-viscosity of the internal phase will depend on the viscosity of the micelle