Coarse Dispersions 2 Flashcards Preview

Ceutics: Module 3 > Coarse Dispersions 2 > Flashcards

Flashcards in Coarse Dispersions 2 Deck (22)
Loading flashcards...

What is an emulsion?


a mixture of immiscible liquids, in which one phase is dispersed as small droplets of a liquid throughout the other phase (vehicle)
Thermodynamically unstable system


Components of an Emulsion

Dispersed phase: internal phase, droplets, globules, 
0.1 ~ 10 m
Dispersion medium: external phase or continuous phase. 
Emulsifying agent (s): generally added to stabilize emulsion (emulsifier, emulgent)

How are emulsions classified?


Water-in-oil (w/o) emulsions
Oil-in-water (o/w) emulsions
Multiple emulsions (o/w/o, w/o/w, …): for control release system; less stable
Microemulsion (colloidal or fine dispersions): 1nm-1m, transparent or translucent
Classification by viscosity of emulsions
Liquid emulsions: oral, topical or parenteral Semisolid emulsions: topical creams and lotions


Methods to determine the type of emulsion


Use of water-soluble dye such as methylene blue:
If water is the external phase (o/w ), the dye will dissolve and uniformly diffuse throughout the water. If the emulsion is of the w/o type, the particles of dye will lie in clumps on the surface.

Dilution of the emulsion with water: If the emulsion mixes freely with the water; o/w

using a pair of electrodes connected to an external electric source and immersed in the emulsion:
If the external phase is water, a current will pass through the emulsion. If the oil is the continuous phase, the emulsion fails to carry the current.


Reasons for preparing emulsions


To prepare stable and homogeneous mixtures of two immiscible liquids
To reduce droplet size: emulsion permits the administration of a liquid drug in small globules, which are more readily absorbed and/or more digestible
For orally administering water-insoluble liquids, especially when the dispersed phase has an unpleasant taste emulsions; o/w oral emulsion can mask the distasteful oil.
For intravenous: o/w, in patients who are unable to assimilate materials administered orally
intramuscular : w/o for extended release
For externally use to the skin, maybe o/w or w/o


Selection of Emulsions used externally


Selection of o/w or w/o emulsions depending on:
The nature of the therapeutic agents and its therapeutic purpose
Skin irritating drugs generally become less irritating if present in the internal phase
Condition of skin surface
The desirability for emollient or tissue softening effect
e.g. Choose w/o emulsion when:
On the unbroken skin; Can be applied more evenly: because the skin is covered with a thin film of sebum and this surface is more readily wetted by oil than by water.
Being more softening to the skin: because it resists drying out and is resistant to removal by contact with water.


What are the Theories of Emulsification?


Surface tension theory
Oriented-wedge theory
Plastic or interfacial film theory


What is the surface tension theory?


A good model for to explain emulsification initiation by surfactants

  • a liquid drop tend to have a shape with the minimal surface area; spherical
  • In a spherical drop of liquid, there are internal forces that tend to promote the association of the molecules to resist the distortion of the sphereWhen two or more drops of the same liquid come into contact with one another, they tend to join or to coalesce When the liquid is in contact with an immiscible second liquid, the interfacial tension force causing each liquid to resist breaking up into smaller particles

surfactants (as emulsifiers) are tension-lowering substances:


What is the Oriented-Wedge Theory?


The oriented-wedge theory assumes monomolecular layers of emulsifying agent curved around a droplet of the internal phase of the emulsion.
Based on the presumption that certain emulsifying agents orient themselves about and within a liquid in a manner reflective of their solubility in that particular liquid.
It predicts – The phase, in which the emulsifying agent is more soluble, will become the continuous or external phase of the emulsion.
Hydrophilic emulsifiers – oil-in-water emulsion
Hydrophobic emulsifiers – water-in-oil emulsion


What is the Plastic or Interfacial Film Theory?


The plastic (-interfacial) -film theory places the emulsifying agent at the interface between the oil and water, surrounding the droplets of the internal phase as a thin layer of film adsorbed on the surface of the drops.
The film prevents the contact and coalescing of the dispersed phase
The tougher and more pliable the film, the greater the stability of the emulsion.
A good model to explain stability


Types of Emulsifying Agents?


A. Surface-active agents, which are adsorbed at oil–water
Interfaces to form monomolecular films and reduce interfacial tension.

B. Hydrophilic colloids (Macromolecules)
Form a multi-molecular film around the dispersed droplets;
Carbohydrate materials (polysaccharides)
O/W: Acacia, Tragacanth, agar, chondrus, and pectin, Microcrystalline cellulose
Protein substances
O/W: Gelatin, Egg yolk or white, Casein
High molecular weight alcohols
O/W: Stearyl alcohol, cetyl alcohol,
W/O: Cholesterol and cholesterol derivatives

C. Finely Divided Solids (Colloidal Clays)
adsorbed at the interface between two immiscible liquid phases


Finely Divided Solids (Colloidal Clays)


Mechanism: Solid particles adsorbed at the interface produce a particular film around droplets to prevent coalescence.
To prepare o/w emulsions,
When the powdered solid is added to the aqueous phase
And the aqueous phase volume > the oleaginous phase.
Form w/o emulsion
When the powdered solid is added to the oil
And the oleaginous phase volume > aqueous phase
Magnesium hydroxide
Aluminum hydroxide


Mechanism and requirements of an emulsifier


Emulsifying agent
Emulsification: promote (or initiate) emulsification
Stabilization: maintain the stability of emulsions

General requirement of emulsifiers as an excipients
Compatible with the other formulate ingredients (excipients)
Not interference with the stability or efficacy of the therapeutic agent(s) (API)
Stable and do not deteriorate in the preparation
Nontoxic with respect to its intended use and the amount
With little odor, taste, or color


The stability of an emulsion means


absence of coalescence of the internal phase,
absence of creaming,
Maintenance of its physical properties.


Classifying the Instability of Emulsions


(a) Flocculation and creaming
(b) Coalescence and breaking
(c) Phase inversion
(d) Miscellaneous physical and chemical changes


What is creaming?


Creaming resulting from flocculation and concentration of the globules of the internal phase
may not result in coalescence – aggregates of globules of the internal phase rise to the top of the emulsion or fall to the bottom.
Upward creaming – internal phase has a lesser density
Downward creaming – external phase has lesser density
Creaming is a reversible process – creamed portion of an emulsion may be redistributed rather homogeneously upon shaking (comparable to flocculation)
Creaming is NOT desirable
It increases the risk of the coalescing of the globules.
Difficult to disassemble: improper dosage of the internal phase substance may result, if insufficient shaking is employed before each dose
not acceptable for patients and not appealing


What is coalescence?


Coalescence – “breaking” of globules
Coalescence is separation of internal phase globules into a separate layer; greater destruction than creaming.
Coalescence is irreversible – the protective sheath about the globules of the internal phase no longer exists
Therefore, additional emulsifying agent and reprocessing through appropriate machinery are usually necessary to produce and recover


What is a phase inversion?


Inversion – the emulsion changes from an o/w emulsion to a w/o, or vice versa.


Factors that influence the flow properties of emulsions


Most emulsions are non-Newtonian systems
The factors related to the dispersed phase :
- phase–volume ratio (e.g. When the volume concentration approaches 74 %, inversion may occur
- The particle size distribution
the viscosity of the internal phase
Emulsifying agent
Viscosity of the continuous phase


Preservation against microorganisms


Increase the stability by preservation against microorganisms contaminating (Molds, yeasts, and bacteria), which can decompose the emulsifying agent and disruption of the system.
Fungistatic preservatives are generally included in the aqueous phase of an o/w emulsion.
Methy-/Ethyl-/Propyl-/Butyl-paraben; Benzoic acid
Benzalkonium chloride
Alcohol (12 to 15%) added to orally used o/w emulsions for preservation.


Small scale methods of emulsion preparation

Continental (dry gum) method: oil:water:emulsifier = 4:2:1  the emulsifying agent (usually acacia) is mixed with the oil before the addition of water, 
English (wet gum) method: emulsifying agent (water soluble) + water firstly; form a mucilage, then slowly add the oil.
Bottle method(Forbes bottle): for volatile or less viscous oils, similar to dry gum method

Examples of emulsions

Injectable Emulsions
Topical Emulsions: lotions, creams,
Oral Simethicone Emulsion
Oral Castor Oil Emulsion
Oral Mineral Oil Emulsion