Medicinal Emulsions Flashcards
What is an emulsion?
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.
Oil in water O/W
-Oil is the disperse phase
-water is the continuous phase
-used invariably for oral and IV medicines
Water in oil w/o
-water is the disperse phase
-oil is the continuous phase
-mainly external use as emolients although can be used as IM or ‘depot’ injections
what is a microemulsions
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
characteristics of microemulsions
-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
what does hydrophobic, hydrophyilic, lipophobic, lipophilic mean?
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.
How to dermine if a crude emulsion is o/w or w/o
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
How to dermine if a crude emulsion is o/w or w/o
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
What is interfacial tension
The reason why oil and water are not miscible in the absense of an emulsifying agent
Interfacial tension
-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
Stabalisation of emulsions
-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.
Emulsifying agents
-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
two main categories of emulsifying agents
Ionic
Non-ionic
Ionic EA
- 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
Non-ionic EA
Glyceral monostearte more suitable as oral medicinal surfactant
Oral emulsions
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.
Intravenous emulsions
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
Topical emulsion
-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.
Hydrophilic/Lipophilic balance (HLB)
-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
hydrophilic and lipophilic favouring
Hydrophilic will favour o/w emulsions
Lipophilic will favour w/o emulsions
HLB values
-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
describe the hlb of spans and tweens
Spans (sorbital esters) are low HLB values - Lipophilic
Tweens (polyoxyethylene derivatives of the spans) are high HLB values - Hydrophilic
HLB values scale
Lipophilic
HLB 0-9
w/o emulsifying agents
Hydrophilic
HLB 12-18
o/w emulsifying agents
Required HLB (RHLB)
-the oil phase of an o/w emulsion requires a specific HLB
-the oil phase of a w/o emulsion requires a specific HLB
Calculation of RHLB
- Calculate the overall RHLB of the emulsion based on the weight fraction of each component
- multiply each RHLB by the weight fraction - 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
RHLB calculation continued
Ideal emulsion
-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
ideal emulsifying agent
-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
Macroscopic evaluation
degree of creaming = volume of total cream or sediment / total volume
Accelerated stability
storage at adverse temperatures (high or low)
cetrifuation at 200-300rpm (increase sedimentation)
Viscosity of emulsions
-the viscosity of emulsions will vary greatly depending on their composition and application
-most emulsions (except dilute ones) exhibit non-newtonian flow
visocosity of emulsions - disperse phase
phase-volume ratio - newtonian <0.05
pseudoplastic >0.05
plastic flow»_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
