As defined by the USP XVII an
emulsion is a two-phase system in which one liquid is dispersed in the form of
small globules throughout another liquid. The dispersed liquid is known as the
internal phase, whereas the dispersion medium as the external or continuous
phase. Oil-in-water (O/W) emulsion is when oil is the dispersed phase and an
aqueous solution is the continuous phase. Conversely, water-in-oil (W/O)
emulsion is when water or an oleaginous material is the continuous phase.
Emulsion may also be defined as an intimate mixture of two immiscible liquids
held together by an intermediate agent. The intermediate agent responsible for
making a stable emulsion is called the emulsifying, dispersing or stabilizing
agent.
It is very important to bear
in mind that while droplets of one immiscible liquid dispersed in another
constitutes an emulsion according to Becher, “a third component may be added to
accentuate the minimal stability of an emulsion.” This third component is one
of the most important factors in the development of an acceptable emulsion
product both in pharmaceutical and cosmetic point of view.
And this third component is
called emulsifying agent.
Emulsifying
agents are divided into 3 broad groups:
1. Natural Emulsifying Agents are substances derived either from
animal or vegetable sources. Examples of those obtained from animals are
gelatin, egg yolk, casein, wool fat and cholesterol. From vegetable sources are
acacia, tragacanth, chondrus and pectin.
2. Finely Divided Solid Agents are bentonite, magnesium hydroxide, and
aluminum hydroxide and magnesium trisilicate.
3. Synthetic Emulsifying Agents are agents which can be further
divided into anionic, cationic and nonionic agents. Example of anionic is
sodium lauryl sulfate, cationic like benzalkonium chloride and nonionic like
polyethylene glycol 400 monostearate.
The NF XII suggests that only
O/W emulsions are suitable for oral use because these are water-miscible and
thus their oiliness is masked. The NF gives specific directions for the
preparation of emulsions utilizing gelatin as an emulsifying agent. These preparations are based on either Type
A or Type B gelatin.
Type A Gelatin
Type A gelatin is prepared from
acid-treated precursors and is used at a pH of about 3.2. It is compatible with
anionic emulsifying agents such as the vegetable gums.
Formula:
Gelatin (Type A) 8 g
Tartaric Acid 0.6 g
Flavor, as desired
Alcohol 60 ml
Oil 500 ml
Purified Water, q.s. __________
To make 1000 ml
Preparation: Add the gelatin and tartaric acid to about 300 ml of
purified water; allow standing for a few minutes. Heat the mixture until the
gelatin is dissolved, then raise its temperature to about 98o and
maintain this temperature for about 20 minutes. Cool to 50o, add the
flavor, the alcohol, and sufficient purified water to make 500 ml. Add the oil,
agitate the mixture thoroughly and pass it through the homogenizer or a colloid
mill until the oil is completely and uniformly dispersed.
This emulsion cannot be
prepared by trituration or by the use of the usual stirring devices.
Type B Gelatin
Type B Gelatin is prepared
from the alkali-treated precursors and is used at a pH of about 8. It may be
employed with other anionic emulsifying agents but is contains 50% oil, 5 grams
of Type B Gelatin, 2.5 grams of NaHCO3 and sufficient tragacanth or
agar should be incorporated into the aqueous phase so as to yield 1000 ml of
product of the required viscosity.
O/W and W/O, are emulsion type
of lesser significance if the final preparation is to be applied to the skin,
if there are no breaks in the skin, a W/O emulsion can be thin film of sebum.
The latter substance favors the oily choice of emulsion type will, however,
depend on many other factors. Although there are a few commercial products
classified under the title “emulsions”, they are of great significance as bases
for other types of preparations, particularly in the dermatological and
cosmetic areas. Emulsions possess a number of advantages over other liquid
forms.
Advantages of Emulsions
1. The therapeutic properties
and the spreading ability of the constituents are increased. However, at times
this may be a disadvantage because it is reported in the NF that water-soluble antiseptics
are more active but also potentially more irritating when incorporated into an
O/W emulsion.
2. Unpleasant taste or odor of
the oil can be partially or wholly masked by the process of emulsification.
Only a minimal amount of flavors and sweetening agents should be added to
emulsions in order to prevent nausea or gastric distress that results on
ingestion of larger quantities of those formulation aids.
3. The absorption and
penetration of medicaments are more easily controlled if they are incorporated
into an emulsion.
4. Emulsion action is more
prolonged and the emollient effect is greater than that observed with
comparable preparations.
5. Water is not only an
inexpensive diluent but is of great value as a solvent for many drugs and
flavors that are incorporated into emulsions.
Discussion:
Aqueous phase favors the
growth of microorganisms so that a preservative is usually added to the
product. Mixtures of methylparaben and propylparaben and alcohol is suitable as
preservatives, the latter is added to the external phase (O/W) in a
concentration of 12 to 15% based on the volume of water used in the
preparation.
Selection of the emulsifying
agent or agents is one of the more important problems. Success and failure in
producing an emulsion is largely dependent on the emulsifying agent and agents
in the formula. As with all other products to be used in medical practice, the
potential toxic effect of every ingredient added to a formulation must be
evaluated in relationship to the use of an emulsion. Thus, an emulsifying agent
quite suitable for a dermatological product might be entirely unacceptable for
an intravenous emulsion. Up to 1950 the selection of emulsifying agents for an
emulsion formula was primarily an empirical or “trial and error” procedure.
Griffin’s pioneering work, however, provided a more logical procedure for
selecting emulsifying agent (surfactants). Griffin’s method is known as the HLB
(hydrophile-lipophile-balance) method and is used by many product development
groups in formulating new products.
Griffin assigned numerical
values to each surface active agent, ranging from 1 to 40, to express the
polarity or hydrophilic the substance. Through experiments Griffin was able to
categorize this HLB values to fit specific applications. If W/O emulsion is
desired only those emulsifying agents having an HLB value falling in the range
of 3 to 6 should be considered; and for an O/W emulsion only those agents
falling in the range of 8 to 18 need be appraised. In the HLB system values are
assigned both to the emulsifying agents and to the oil and oil-like
ingredients.
To prepare an emulsion having
good stability one must employ emulsifying agents having the same or nearly the
same HLB as the oil phase. For example, if cottonseed oil is to be used for and
O/W emulsion, it will be necessary to have a emulsifying agent or agents with
an HLB of 7.5. One of the most important aspects of the HLB system is that the
values are algebraically additive; to give a specific HLB. Blends of
emulsifying agent, for which reason the formulator may begin the development of
an emulsion using two emulsifying agents. In formulating a new emulsion formula
it is necessary first to find the HLB of the oil phase, then the second step is
that of blending two emulsifying agents to give the desired HLB of the oil.
At times, for example, with a
new type of oil the HLB value of the oil may not be known and it becomes
actually necessary to determine the HLB, in such cases, experiments should be conducted
with a pair of emulsifying agents compounded in various rations to give
definite HLB’s ranging from low values to high values. From the series of
emulsions thus prepared, the best one is selected and the HLB of the particular
combination of emulsifying agents used in the formula is assigned to the oil.
Generally, for more precise determination of HLB values, several series of
emulsions may have to be made before the proper HLB value is ascertained.
Preparation: A practicing pharmacist
has many opportunities to apply his knowledge of emulsions and emulsification
in practice, including the preparation of emulsion on prescription order, which
often requires special treatment to effect suspension or emulsification of some
troublesome ingredient. Although hand homogenizers and electric mixers are
considered at present normal equipment for the pharmacy, there are occasions
when the pharmacist must rely solely upon the mortar and pestle using either
the English Method or Continental Method.
