Emulsion

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Emulsion

• Definition
• Applications
• Classification
• Theory of emulsification
• Stability of emulsion
• Preservation of emulsion
• Emulsion preparation
• Nascent method
• Dry gum
• Wet gum
• Incorporation of drugs into emulsion
• Microemulsion

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Emulsion
An emulsion is a thermodynamically unstable
system consisting of at least two immiscible
liquid phases, one of which is dispersed as
globules in the other liquid phase, stabilized by
the presence of an emulsifying agent.
A. Two immisicble liquids, not emulsified B.
An emulsion of Phase B dispersed in Phase A C.
The unstable emulsion progressively separates
D. The (purple) surfactant positions itself on
the interfaces between Phase A and Phase B,
stabilizing the emulsion
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Pharmaceutical application of emulsions

• O/W emulsion is convenient for oral dosing
• To cover unpleasant taste
• To increase oral absorption
• I.V. O/W, if oral o/w not possible (RES uptake)
• External use (topical cream)

A broad-spectrum antifungal agent administered
orally to treat a variety of fungal infections.
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Emulsion types

• Types
• Oil-in-water (o/w)
• Water-in-oil (w/o)
• Oil-in-water-in-oil (o/w/o)
• Water-in-oil-in-water (w/o/w)
• Determination of o/w or w/o
• Water soluble dye (e.g., methylene blue)
• Dilution of emulsions
• Conduction of current

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Theory of emulsification
Change from A to B will significantly increase of
the surface area of phase. e.g., if 1 cm3 of
mineral oil is dispersed into globules having
diameter of 0.01 mm in 1 cm3 of water, how much
will be the surface area increased. The surface
area will become 600 m2 (greater than a
basketball court) the surface free energy will
increase by 8 calories. Therefore, emulsions are
thermodynamically unstable, and the droplets have
the tendency to coalesce. Emulsifying agents are
needed to decrease the surface tension and to
stabilize the droplets.
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Classification of emulsifying agents

• Surface active agents (monomolecular film)
• Hydrophilic colloids (multimolecular film)
• Finely divided solid particles (Particulate film)

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Monomolecular adsorption
Rule of Bancroft The type of the emulsion is a
function of the relative solubility of the
surfactant, the phase in which it is more soluble
being the continuous phase.
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Multimolecular adsorption and film formation

• 1. Hydrated lyophilic colloids (hydrocolloids)
• providing a protective sheath around the droplets
  
• imparting a charge to the dispersed droplets (so
  that they repel each other)
• swelling to increase the viscosity of the system
  (so that droplets are less likely to merge)
• 2. Classification of hydrocolloids
• vegetable derivatives, e.g., acacia, tragacanth,
  agar, pectin, lecithin
• animal derivatives, e.g., gelatin, lanolin,
  cholesterol
• Semi-synthetic agents, e.g., methylcellulose,
  carboxymethylcellulose
• Synthetic agents, e.g., carbomers (PEG and
  acrylic acid)

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Solid particle adsorption

• Description Finely divided solid particles that
  are wetted to some degree by both oil and water
  can act as emulsifying agents. This results from
  their being concentrated at the interface, where
  they produce a particulate film around the
  dispersed droplets to prevent coalescence.
• Example of agents bentonite (Al2O3.4SiO2.H2O),
  veegum (Magnesium Aluminum Silicate), hectorite,
  magnesium hydroxide, aluminum hydroxide and
  magnesium trisilicate
• Auxiliary Emulsifying Agents
• A variety of fatty acids (e.g., stearic
  acid), fatty alcohols (e.g., stearyl or cetyl
  alcohol), and fatty esters (e.g., glyceryl
  monostearate) serve to stabilize emulsions
  through their ability to thicken the emulsion.
  Because these agents have only weak emulsifying
  properties, they are always use in combination
  with other emulsifiers.

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Auxiliary emulsifying agents
Auxiliary (secondary) emulsifying agents include
those compounds that are normally incapable
themselves of forming stable emulsion. Their main
values lies in their ability to function as
thickening agents and thereby help stabilize the
emulsion.
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Physical stability of emulsion

• Creaming
• Creaming is the upward movement of dispersed
  droplets of emulsion relative to the continuous
  phase (due to the density difference between two
  phases)
• Stokes law dx/dt d2 (?i-?e)g/18h
• dx/dt rate of setting
• D diameter of particles
• ? density of particles and medium
• g gravitational constant
• h viscosity of medium

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Physical stability of emulsion

• Breaking, coalescence, aggregation
• Breaking is the destroying of the film
  surrounding the particles.
• Coalescence is the process by which emulsified
  particles merge with each to form large
  particles.
• Aggregation dispersed particles come together
  but do not fuse.
• The major fact preventing coalescence is the
  mechanical strength of the interfacial film.

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Physical stability of emulsion

• Phase inversion
• An emulsion is said to invert when it changes
  from an o/w to w/o or vice versa.
• Addition of electrolyte
• Addition of CaCl2 into o/w emulsion formed by
  sodium stearate can be inverted to w/o.
• Changing the phasevolume ratio

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Preservation of emulsions

• Growth of microorganisms in emulsions
• Preservatives should be in aqueous phase.
• Preservatives should be in unionized state to
  penetrate the bacteria
• Preservatives must not bind to other components
  of the emulsion

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Methods of emulsion preparation

• Continental or dry gum method
• English of wet gum method
• Bottle or Forbes bottle method
• Auxiliary method
• In situ soap method
• Calcium soaps w/o emulsions contain oils such
  as oleic acid, in combination with lime water
  (calcium hydroxide solution, USP). Prepared by
  mixing equal volumes of oil and lime water.

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Nascent soap

• Oil phase olive oil/oleic acid olive oil may
  be replaced by other oils, but oleic acid must be
  added
• Lime water Ca(OH)2 should be freshly prepared.
• Equal volume of oil and lime water
• The emulsion formed is w/o or o/w?
• Method of preparation
• Bottle method
• Mortar method when the formulation contains
  solid insoluble such as zinc oxide and calamine.

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Dry gum method (421 method)

• The continental method is used to prepare the
  initial or primary emulsion from oil, water, and
  a hydrocolloid or "gum" type emulsifier (usually
  acacia). The primary emulsion, or emulsion
  nucleus, is formed from 4 parts oil, 2 parts
  water, and 1 part emulsifier. The 4 parts oil and
  1 part emulsifier represent their total amounts
  for the final emulsion.
• In a mortar, the 1 part gum (e.g., acacia) is
  levigated with the 4 parts oil until the powder
  is thoroughly wetted then the 2 parts water are
  added all at once, and the mixture is vigorously
  and continually triturated until the primary
  emulsion formed is creamy white.
• Additional water or aqueous solutions may be
  incorporated after the primary emulsion is
  formed. Solid substances (e.g., active
  ingredients, preservatives, color, flavors) are
  generally dissolved and added as a solution to
  the primary emulsion. Oil soluble substance, in
  small amounts, may be incorporated directly into
  the primary emulsion. Any substance which might
  reduce the physical stability of the emulsion,
  such as alcohol (which may precipitate the gum)
  should be added as near to the end of the process
  as possible to avoid breaking the emulsion. When
  all agents have been incorporated, the emulsion
  should be transferred to a calibrated vessel,
  brought to final volume with water, then
  homogenized or blended to ensure uniform
  distribution of ingredients.

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Preparing emulsion by dry gum method

• Cod liver oil 50 mL
• Acacia 12.5 g
• Syrup 10 mL
• Flavor oil 0.4 mL
• Purified water, qs ad 100 mL

• Accurately weigh or measure each ingredient
• Place cod liver oil in dry mortar
• Add acacia and give it a very quick mix
• Add 25 mL of water and immediately triturate to
  form the thick, white, homogenous primary
  emulsion
• Add the flavor and mix
• Add syrup and mix
• Add sufficient water to total 100 mL

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Wet gum method

• In this method, the proportions of oil, water,
  and emulsifier are the same (421), but the
  order and techniques of mixing are different. The
  1 part gum is triturated with 2 parts water to
  form a mucilage then the 4 parts oil is added
  slowly, in portions, while triturating. After all
  the oil is added, the mixture is triturated for
  several minutes to form the primary emulsion.
  Then other ingredients may be added as in the
  continental method. Generally speaking, the
  English method is more difficult to perform
  successfully, especially with more viscous oils,
  but may result in a more stable emulsion.

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Bottle method

• This method may be used to prepare emulsions of
  volatile oils, or oleaginous substances of very
  low viscosities. This method is a variation of
  the dry gum method. One part powdered acacia (or
  other gum) is placed in a dry bottle and four
  parts oil are added. The bottle is capped and
  thoroughly shaken. To this, the required volume
  of water is added all at once, and the mixture is
  shaken thoroughly until the primary emulsion
  forms. It is important to minimize the initial
  amount of time the gum and oil are mixed. The gum
  will tend to imbibe the oil, and will become more
  waterproof.

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Auxiliary method

• An emulsion prepared by other methods can also
  usually be improved by passing it through a hand
  homogenizer, which forces the emulsion through a
  very small orifice, reducing the dispersed
  droplet size to about 5 microns or less.

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Incorporation of medicinal agents

• Addition of drug during emulsion formation
• Addition of drugs to a preformed emulsion
• 1. Addition of oleaginous materials into a w/o
  emulsion
• 2. Addition of oleaginous materials to an o/w
  emulsion
• 3. Addition of water soluble materials to a
  w/o emulsion
• 4. Addition of water soluble materials to an
  o/w emulsion

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Microemulsion

• Microemulsions are thermodynamically stable,
  optically transparent, isotropic mixtures of a
  biophasic oil-water system stabilized with
  surfactants.

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Pharmaceutical applications of microemulsions

• Increase bioavailability of drugs poorly soluble
  in water
• Topical drug delivery systems

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Preparation of nanoparticles from microemulsion
precursors