pharmaceutical compounding ii lecture 7 emulsions, part 2 pharmaceutical compounding ii lecture 7...

Pharmaceutical Compounding II

Lecture 7 Emulsions, Part 2

Dr. Twana Mohammed M. Ways

2019-2020

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Outline of the lecture

• Formation of emulsions

• Stabilization of emulsions

• Mechanism of action of emulsifying agents

• Scale of emulsion formation

• Methods for preparation of emulsions

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Formation of emulsions

• The preparation of stable emulsions depends on how well theformulator can:

1. Disperse one liquid as droplets in another.

2. Stabilize this dispersion against coalescence or fusion of thedroplets, which ultimately would result in the return of thesystem to its original state (i.e. two separate liquid phases).

• A successful formulation is one in which dispersion isoptimized and maintained, while any coalescence isminimized.

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Dispersion and coalescence of droplets

1. Dispersion

• If two immiscible liquids in contact with each other areshaken vigorously, the interface between them firstbecomes distorted.

• Fingers of liquid penetrate the opposing phase from whichdroplets break off and are dispersed in the other liquid.

• Thus, in a mixture of oil and water, oil droplets in waterand water droplets in oil will form simultaneously.Therefore, a dispersion (which in this case it means anemulsion) is formed.

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2. Coalescence

• Coalescence is the actual fusion of two or more liquiddroplets to form a larger droplet. Stabilization (i.e. preventionof coalescence) is achieved by the addition of an effectiveemulsifying agent which is adsorbed at the interface betweenthe dispersed droplets and the dispersed medium.

• Coalescence is preceded by flocculation and is usually quiterapid because of relatively small energy barrier opposing theirfusion.

Dispersion and coalescence of droplets

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Stabilization of emulsions

• Emulsions are stabilized by the presence of a film that isformed at the interface between the oil and water phases.

• The material that is adsorbed to form this film is referred toas the emulsifying agent.

• There are three types of the film which are:1. Monomolecular (monolayer) film2. multimolecular (multilayer) film3. solid particles film

See next figure and tables.

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o/w emulsion

Monomolecularfilm

Multimolecularfilm

Solid particlefilm

Types of films formed by emulsifiers at the oil/water interface

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Mechanism of action of emulsifying agents

MechanismExampleType of Film

Coherent, flexible film formed by surface active agents. These agents significantly lower interfacial tension, and thus contributes to the stability of emulsion. Are widely used, especially the non-ionic type.Depending on the particular agent(s) chosen, can prepare o/w or w/o emulsion.

Potassium laurate,Polyoxyethylenesorbitanmomooleate

Monomolecular

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Strong, rigid film around the emulsion globules formed, mostlyby hydrocolloids which produceo/w emulsion. Interfacial tension is not reduced to any degree; however they mainly stabilize the emulsion due to the strength of the interfacial film.They also enhance the stability of emulsions by increasing the viscosity of the continuous phase.

Acacia, GelatinMultimolecular


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Film formed by solid particles that aresmall in size compared to the droplets ofdispersed phase. Particles must be wetted by bothphases to some extent in order to remainat the interface and form a stable film.Can form either o/w or w/o emulsions,depending on the method ofpreparation.

Bentonite,Magnesium hydroxide

Solid particles


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Affinity of emulsifiers to the interface

• Generally, the emulsifying agents must have a degree of affinity for the interface between the two phases.

• With the monomolecular and multilayer films, the emulsifyingagent must be soluble in both phases to some extent. However, itshould not be too soluble in any one phase; otherwise, it will not beadsorbed to the interface but instead will remain in the bulk of thatphase.

• A similar balance must exist for solid particles that function asemulsifying agent. If wetted too strongly by either phase, theparticles will move into that bulk phase rather than remain at theinterface.

• Additionally, the particles must be small compared to the size of theemulsion droplets.

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What factors determine the type of emulsion?

1. The proportion of the dispersed phase and thecontinuous phase:

• Generally, the larger of the two phases present will becomethe continuous phase.

2. The emulsifying power of the emulsifier:

• This is more important than the proportion of the phasese.g. an emulsifying agent with a well developed capabilityto form stable o/w emulsions can often form an o/wemulsion composed of 80% oil dispersed as droplets in 20%water.

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Scale of emulsion formation

1. Small scale processing:• Wedgwood or porcelain mortar and pestle are often used in the

laboratory or pharmacy for the small scale preparation ofemulsions.

• The glass mortar and pestle is often unsatisfactory for this purpose,since the surfaces are not rough to create adequate shearnecessary for the proper grinding and the reduction of the globulesize.

• A mechanical blender or mixer, such as a Waring blender or amilkshake mixer, a hand homogenizer, a bench-type homogenizer,or sometimes a simple prescription bottle are also used for thepreparation of small batches of emulsions.

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Hand homogenizer

Bench-type homogenizer

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2. Large scale processing:

• Same for suspensions.• large mixing tanks (next figure) may be used to form the

emulsion through the action of a high-speed impeller.

• As desired, the product may be rendered finer by passagethrough a colloid mill, in which the particles are shearedbetween the small gap separating a high-speed rotor andthe stator, or by passage through a large homogenizer, inwhich the liquid is forced under great pressure through asmall valve opening.

• Industrial homogenizers have the capacity to handle asmuch as 100,000 L of product per hour.

Scale of emulsion formation:

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16An industrial mixer for manufacture of dispersesystems, including suspensions and emulsions.

Methods for preparation of emulsions

1. Addition of internal phase to external Phase (Wet Gum,English, or American method):

• The easiest and most frequently used sequence for emulsionpreparation is by the gradual addition of the internal phase tothe external phase.

• Prior to mixing, all water-soluble ingredients are dissolved inthe aqueous phase and all oil-soluble components aredissolved in the oil.

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1. Addition of internal phase to external Phase (Wet Gum, English, or American method):

• When all soluble components have been dissolved in theirrespective phases, the oil phase is added gradually to theaqueous phase which is stirred continuously. In this way,the external phase is water.

• If a w/o emulsion is being prepared, the reverse procedurewill be carried out (i.e. the aqueous phase is graduallyadded to the oil phase).

• On a small scale, such emulsions can be readily prepared ina beaker equipped with a variable speed stirrer, or thecomponents can be added to a bottle and then shaken.

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• If fats, waxes or surfactants that are solid or semisolid atroom temperature are used in the formulation, it will benecessary to warm the two phases so that, before mixing,two homogeneous liquid phases are produced.

• Invariably, the aqueous phase is raised to a temperaturethat is 2 to 3 ⁰C above that of the oil phase, irrespective ofwhether it is the internal or external phase. This ensuresthat no local crystallization of waxes takes place from theoil when the phases are mixed, since this could produce acoarse grained product of low stability and poorappearance.


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• If the formulation of an o/w emulsion contains strongelectrolytes, these are often not added to the aqueousphase until after the emulsion has been formed; why?

• When a hydrophilic gum, such as acacia or tragacanth, isused as emulsifying agent, a primary or concentratedemulsion is first prepared using a set ratio of oil, waterand gum according to the next table.


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Ratios of oil: water: emulsifier

Emulsifying agent Liquid petrolatum, linseed oil and volatileoils

Fixed oil exceptliquid petrolatumand linseed oil

3:2:1 or 2:2:14:2:1Acacia

30:20:1 or 20:20:140:20:1Tragacanth

Ratios of oil: water: emulsifier to prepare emulsions

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• To make 60 mL of the following o/w emulsion (which is called codliver oil emulsion), containing 50% cod liver oil:

Cod liver oil 30 mL

Acacia powder qs

Purified water qs ad 60 mL

A ratio of oil: water: gum equals to 4:2:1 should be employed toprepare the primary emulsion.

Thus, two part of water (15ml) are added all at once to 7.5 g of acaciain a mortar and the mixture triturated with the pestle to produce asmooth dispersion.

1. Addition of internal phase to external Phase (Wet Gum, English, or American method); How to prepare cod liver oil

emulsion?

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How to prepare cod liver oil emulsion?

• The oil (30 mL) is then added slowly in small increments of 1to 5 mL, with continuous trituration so that each portion isdistributed and emulsified in the mucilage before the nextquantity is added. The primary emulsion, once formed, istriturated for at least 5 minutes to ensure complete dispersionof the oil and is then diluted with the required amount ofwater to bring the product to the final volume.

• When gum used as emulsifier it called Wet Gum method.

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2. Addition of external phase to internal Phase (Dry Gum method)

• If small batches are to be prepared using hydrophilic gums asemulsifiers, the general procedure is as follows:

• The oil and powdered acacia are mixed in a dry mortar untilthe powder is distributed uniformly throughout the oil.

• A measured portion of water is added all at one time and,immediately, the whole is triturated to form a primaryemulsion.

• Finally, the remaining water and other water-solublecomponents are added to complete the product.

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• Using previous example (cod liver oil emulsion); the 4 partsof oil (30 mL) are mixed in a dry mortar with 1 part ofpowdered acacia (7.5 g) (one or two minutes may berequired to distribute the gum evenly throughout the oil).

• To the oil and the well-dispersed emulsifying agent, 2 partsof purified water (15 mL) are added all at once, and theprimary emulsion is formed by light rapid trituration.

• The primary emulsion should be triturated for at least 5minutes before dilution, additional water containingflavouring ingredients, preservatives, and water-solubledrugs, may then be incorporated.

2. Addition of external phase to internal Phase (Dry Gum method)

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Thanks

Questions?

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