Choice of emulsifying agent by 2i48203

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									Choice of emulsifying agent

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       Toxicity and irritancy considerations

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 The choice of emulgent to be used will depend not only
  on its emulsifying ability, but also on its route of
  administration and, consequently, on its toxicity.

 It will be noted that most of these emulsifying agents are
  non-ionic, having a tendency to be less irritant and less
  toxic than their anionic, and particularly their cationic
  counterparts. The concentrations of ionic emulsifying
  agents necessary for emulsification will be irritant to the
  gastrointestinal tract and have a laxative effect, and
  should not be used for oral emulsions.
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 Cationic surfactants in general are toxic even at lower
  concentrations. The emulgent cetrimide is limited to externally used
  preparations, where its antiseptic properties are of use.

 Some emulgents, such as the anionic alkali soaps, often have a high
  pH and are thus unsuitable for application to broken skin. Even on
  normal intact skin with a pH of 5.5, the application of such alkaline
  materials can cause irritation.

 Some emulsifiers, in particular, wool fat can cause sensitization
  reactions in susceptible people.

 When choosing an emulgent for parenteral use it must be realized
  that only certain types of non-ionic material are suitable. These
  include lecithin, polysorbate 80, methylcellulose, gelatin and serum
  albumin.
   The hydrophile–lipophile balance (HLB)
                  concept
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 Each surfactant is allocated an HLB number usually
 on a scale of 0–20, based on the relative proportions
 of the hydrophilic and hydrophobic part of a
 molecule. Water-in-oil emulsions are formed
 generally from oil-soluble surfactants of low HLB
 number and oil-in-water emulsions from more
 hydrophilic surfactants of high HLB number.
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 The method of selection is based on the observation
  that each type of oil will require an emulsifying agent
  of a specific HLB number to produce a stable
  emulsion.
 Thus, oils are often designated two “required” HLB
  numbers, one low and one high, for their
  emulsification to form water-in-oil and oil-in-water
  emulsions respectively. A series of emulsifiers and
  their blends with HLB values close to the required
  HLB of the oil are then examined to see which one
  forms the most stable emulsion.
        "Required HLB" Values of some Ingredients

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                                "Required HLB" for
                     w/o                 o/w
Ingredient                          Emulsion
Acid, Stearic        6                   15
Alcohol, Cetyl       __                  15
Alcohol, Stearyl     __                  14
Lanolin, Anhydrous   8                   10
Fat, Wool            8                   10
Oil, Cottonseed      5                   10
Oil, Mineral         5                   12
Petrolatum           5                   12
Paraffin, Liquid     4                   12
Wax, Beeswax         4                   12
        HLB Values of some Surfactants
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Surfactant                                     HLB
Sorbitan trioleate (Span 85)             1.8
Sorbitan tristearate (Span 65)           2.1
Sorbitan sesquioleate (Arlacel 83)       3.7
Glyceryl monostearate, NF                3.8
Oleic acid                               4.3
Sorbitan monooleate, NF, (Span 80)       4.3
Sorbitan monostearate, NF, (Span 60)     4.7
Sorbitan monopalmitate, NF, (Span 40)    6.7
Sorbitan monolaurate, NF, (Span 20)      8.6
           HLB Values of some Surfactants
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Surfactant                                                                  HLB
Polyoxyethylene sorbitan tristearate, (Tween 65)                         10.5
Polyoxyethylene sorbitan trioleate, (Tween 85)                           11.0
Polyethylene glycol 400 monostearate                                     11.6
Polysorbate 60, NF, (polyoxyethylene sorbitan monostearate) (Tween 60)   14.9
Polyoxyethylene monostearate (Myrj 49)                                   15.0
Polysorbate 80, NF, (polyoxyethylene sorbitan mono-oleate) (Tween 80)    15.0
Polysorbate 40, NF, (Tween 40)                                           15.6
Polysorbate 20, NF, (polyoxyethylene sorbitan mono-laurate) (Tween 20)   16.7
Potassium oleate                                                         20.0
Sodium lauryl (dodecyl) sulphate                                         40.0
             An example of an o/w emulsion:
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Liquid paraffin                          35%
Wool fat                                 1%
Cetyl alcohol                            1%
Emulsifier system                        5%
Water                                    to 100%


 The total percentage of oil phase is 37 (35%+1%+1%) and the proportion of
 each is:


Liquid paraffin            35/37 * 100       = 94.6%
Wool fat                   1/37 * 100        = 2.7%
Cetyl alcohol              1/37 * 100        = 2.7%
    The total required HLB num12/12/2011ber is
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                 obtained as follows:
Liquid paraffin (HLB 12)   94.6/100 * 12   = 11.4 (nearest decimal digit)


Wool fat (HLB 10)          2.7/100 * 10    = 0.3 (nearest decimal digit)


Cetyl alcohol (HLB 15)     2.7/100 * 15    = 0.4 (nearest decimal digit)


Total required HLB                         = 12.1
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 From theoretical considerations, this particular
  formulation requires an emulgent blend of HLB 12.1 in
  order to produce the most stable emulsion. It must be
  realized, however, that the presence of other ingredients,
  particularly those that may partition into the oil phase,
  can also affect the required HLB value.
 It is therefore often necessary to prepare a series of
  emulsions using blends of a given pair of non-ionic
  emulsifying agents covering a wide range of HLB values.
  This is also important if the required HLB for an oil
  phase is not available. The HLB value of the emulgent
  blend giving the most stable emulsion is the required
  value for that oil phase.
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 Assuming that a blend of sorbitan mono-oleate (HLB
 4.3) and polyoxyethylene sorbitan mono-oleate (HLB
 15) is to be used as the emulsifying system, the
 proportions of each to be added to the emulsion to
 provide an HLB of 12.1 are calculated as follows.

 Let A be the percentage concentration of the
 hydrophilic and B the percentage of the hydrophobic
 surfactants required to give a blend having an HLB
 value of x. Then:
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 A=




and

 B = 100 - A
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 In our example, therefore:


 A=                 = 72.9



 B = 100 – 72.9 = 27.1
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 Because the total percentage of emulgent blend in
 the formulation is 5, the percentage of each
 emulsifier will be:


 Sorbitan monooleate                  5 * (27.1/100) = 1.36

 polyoxyethylene sorbitan mono-oleate 5 – 1.36       = 3.64
          Notes on the previous example
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 Although the HLB concept narrows the range of
  emulsifiers to select and provides a schematic approach
  for the formulator, it is limited by its strict relation to
  molecular structure of the individual surfactants.
 The concept does not consider the total emulsion and is
  therefore insensitive to                  between emulsifier
  components, the influence of                       changes, or
  the                                               in the
  emulsion. Consequently, not all emulsifier blends of the
  correct HLB form stable systems.
      Activity and HLB value of emulsifiers
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               Activity           Assigned HLB


Antifoaming               1–3
Emulsifiers (w/o)         3–6
Wetting agents            7–9
Emulsifiers (o/w)         8–18
Solubilizers              15–20
Detergents                13–15
  Phase Inversion Temperature (PIT)
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 The use of the HLB system has several disadvantages,
  including the inability to take into account the effects of
  temperature, the presence of additives and the
  concentration of the emulsifier. It is possible to overcome
  some of these problems.
 An o/w emulsion stabilized by non-ionic emulgents will,
  on heating, invert to form a w/o product. This is because,
  as the temperature increases, the HLB value of a non-
  ionic surfactant will decrease as it becomes more
  hydrophobic. At the temperature at which the emulgent
  has equal hydrophilic and hydrophobic tendencies (the
  phase inversion temperature) the emulsion will invert.

								
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