University of Sulaimani School of Pharmacy Dept. of ... · Dept. of Pharmaceutics Third level - Second semester ... • Emulsifying agents ... • Emulsifying agent could be categorized

University of Sulaimani School of Pharmacy

Dept. of PharmaceuticsThird level - Second semester

Coarse dispersion, emulsions

4/30/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 1


Outlines

• Introduction

• Theories and mechanisms

• Emulsifying agents

• HLB system

• Methods of emulsion preparation

• Microemulsion

• Stability of emulsions

• Common features and differences


Introduction

• An emulsion is a dispersion in which the dispersed phase is composed of small

globules of a liquid distributed throughout a vehicle in which it is immiscible.

• Depending on external and internal phase, emulsions are either water in oil (w/o) or

oil in water (o/w) type.

• The third phase of an emulsion is the emulsifying agent

• Can we dilute emulsion?waterEmulsifierOilW/O O/W


Introduction cont.

• Based on the constituents and the intended application, liquid emulsions may be

employed orally, topically (sometime semisolid), or parenterally.

• Advantages of emulsion

• Preparation of relatively stable and homogeneous mixtures of two immiscible

liquids

• The o/w type permits palatable administration of distasteful oil.

• The reduced particle size of the oil globules may render the oil more digestible

and more readily absorbed


Outlines

• Introduction



• HLB system


• Microemulsion




Theories and mechanisms

1. Surface tension theory

• All liquids have a tendency to assume a shape having the minimal surface area

exposed i.e. sphere.

• If two or more drops of the same liquid come into contact with one another, making

one larger drop having a smaller surface area i.e. coalescence .

• ΔG = γ * ΔΑ

• The force causing each liquid to resist breaking up into smaller particles is called

interfacial tension.


Theories and mechanisms cont.

• Substances that reduce this resistance (encourage a liquid to break up into smaller

drops or particles) is called surface-active (surfactant) or wetting agents.

2. The oriented-wedge theory

• It assumes monomolecular layers of emulsifying agent curved around a droplet of

the internal phase of the emulsion.

• The phase in which the emulsifying agent is more soluble will become the continuous

or external phase

• An emulsifying agent having a greater hydrophilic than hydrophobic character will

promote an o/w emulsion.


Theories and mechanisms cont.

Film type Example MechanismA. Monomolecular Synthetic like,

Potassium laurateTween

• The film is flexible. • They lower the interfacial tension, and thus

contributes to stability of emulsion.

B. Multimolecular Natural likeAcacia, Gelatine

• The film is strong and rigid film formed• The Interfacial tension is not reduced.

C. Solid particles BentoniteMagnesium hydroxide

• Film formed by solid particles that are small in size compared to the dispersed droplet.

• Particles must be wetted by both phases to some extent.


Outlines

• Introduction



• HLB system


• Microemulsion




Emulsifying agents

• Features of emulsifying agents

• The emulsifying agent must be compatible with the other ingredients

• It should be stable

• It should be non toxic and possess a little color, odor, and taste.

• It should be surface active and decrease interfacial tension

• It should be effective in a fairly low concentration


Emulsifying agents

1. Carbohydrate materials like acacia, tragacanth, agar, and pectin generally produce

o/w emulsions.

• Tragacanth and agar are commonly employed as thickening agents in acacia-

emulsified products

• Needs addition of 0.2% of benzoic acid.

2. High molecular weight alcohols, such as stearyl alcohol, cetyl alcohol, and glyceryl

monostearate.

• Usually they are used externally

• Cholesterol is used to promote w/o emulsions.


Emulsifying agents cont.

3. Wetting agents, which may be anionic, cationic, or nonionic

• These agents contain both hydrophilic and lipophilic groups

• Anionic emulsifiers include various monovalent, polyvalent, like sodium lauryl

sulfate

• Benzalkonium chloride is an example for cationic emulsifier

• Agents of the nonionic type include the sorbitan esters and the polyoxyethylene

derivatives,

• Cationic surfactants are effective over pH range of 3 to 7, and anionic

surfactants require a pH greater than 8.


Emulsifying agents cont.

4. Finely divided solids such as colloidal clays, including bentonite, magnesium

hydroxide, and aluminum hydroxide

• Inversion

• Is changing of emulsion from o/w to w/o as a result of increased internal phase.

• Maximum limit of the internal phase is 75%.


Outlines

• Introduction



• HLB system


• Microemulsion




HLB system

• Emulsifying agent has a hydrophilic portion and a lipophilic portion, predominance of

each portion is influence the type of emulsion.

• Emulsifying agent could be categorized on the base of their hydrophilic-liphophilic

balance HLB system.

• The usual range is between 1 and 20.

• Higher polarity → higher the value

• Agents with HLB value of 3 to 6 are

greatly lipophilic and produce w/o

emulsions

• Agents with HLB values of about 8 to

18 produce o/w emulsions.


HLB system cont.

Emulsifier HLB value


Outlines

• Introduction



• HLB system


• Microemulsion




Methods of emulsion preparation

• On a small scale, emulsions may be prepared using porcelain mortar and pestle.

• The product may be rendered finer by passage through a colloid mill.

1. Continental or dry gum method

• The acacia or other o/w emulsifier is triturated with the oil in a dry porcelain (better

than glass) mortar until thoroughly mixed.

• After oil-gum mixing, the two parts of water are added all at once, and the mixture is

triturated immediately → primary emulsion produces a crackling sound (3 min).

• Solution of other ingredients is added into the primary emulsion.

Ratios of Oil: Water: Emulsifier

Emulsifying agentFixed oils except liquid

petrolatum and linseed oilLinseed oil, liquid

petrolatum and volatile oilsAcacia 4:2:1 3:2:1 or 2:2:1

Tragacanth 40:20:1 30:20:1 or 20:20:1


Methods of emulsion preparation cont.

2. English or wet gum method

• Same proportions of oil, water, and gum are used as in dry gum method.

• The order of mixing is different.

• water+acacia trituration → add oil slowly.

3. Bottle method

• It is used for volatile oils or less viscous oils.

• (1 acacia+ 2 oil)→ shaking in a capped bottle. Then adding water equal to the

oil.

Auxiliary

• Homogenizer → 5 μm


Methods of emulsion preparation cont.

4. In situ soap method

• This method includes calcium soaps and soft soaps.

• Calcium soaps are w/o emulsions that contain certain vegetable oils, such as oleic

acid, in combination with limewater (Calcium Hydroxide Solution, USP).

• They are prepared by mixing equal volumes of the oil and limewater.


Outlines

• Introduction



• HLB system


• Microemulsion




Microemulsion

• They are thermodynamically stable, optically transparent mixtures of a biphasic o/w

system stabilized with surfactants.

• Droplet size 10-100 nm.

• The surfactant is commonly called solubilizing agent.

• Advantages

• More rapid and efficient oral absorption of drugs

• Enhanced transdermal drug delivery through increased diffusion into the skin.

• Development of artificial red blood cells and targeting of cytotoxic drugs to

cancer cells


Outlines

• Introduction



• HLB system


• Microemulsion




Stability of emulsions

• Freezing and excessive heat coarsen an emulsion and sometimes break it.

• Fungistatic preservatives, commonly combinations of methylparaben and

propylparaben, are generally included in the aqueous phase of an o/w emulsion.


Stability of emulsions cont.

• An emulsion is considered to be physically unstable if:

a. The internal phase upon standing tends to form aggregates of globules

b. Large globules or aggregates of globules rise to the top or fall to the bottom of

the emulsion

c. If the internal phase separates and forms a distinct layer on the top or bottom

of the emulsion.


Creaming

• Creaming is aggregates of globules of the internal phase that rise to the top of the

emulsion or fall to the bottom.

• It is a reversible process

• A creamed emulsion is not esthetically acceptable

• Thickeners such as tragacanth and MCC are

frequently added to emulsions to increase

the viscosity of the external phase.


Coalescence

• More destructive to an emulsion is coalescence of the globules of the internal phase

and separation of that phase into a layer.

• Separation of the internal phase from the emulsion is called breaking, and the

emulsion is described as being cracked or broken.

• Coalescence and breaking are irreversible.


Outlines

• Introduction



• HLB system


• Microemulsion




Common features and differences between suspensions and emulsions

• Common features

• Suspensions and emulsions contain particles, solid and liquid respectively,

dispersed in a continuous phase.

• They are both subject to sedimentation processes

• The factors that influence the sedimentation rate, operate to the same

extent in both.

• Both systems require some input of energy to disperse the particles


Common features and differences

• Common differences

• The major difference is that the particles of the emulsion are liquid droplets,

whereas those of the suspension are solid.

• In emulsion, droplet aggregation caused coalescence, in suspension caused

flocculation.

• Dissolved drug in oil phase of emulsion is ready for absorption, drug solid

particles need dissolution.


Thank you

Documents

University of Sulaimani School of Pharmacy Dept. of ... · Dept. of Pharmaceutics Third level - Second semester ... • Emulsifying agents ... • Emulsifying agent could be categorized