Pharmaceutical Manufacturing Handbook: Production and

oily phase, and the interfacial layer and act by making the aqueous phase less hydrophilic,
the oily phase less hydrophobic, and the interfacial fi lm more fl exible and less
condensed [9, 10] .
Most single - chain surfactants do not suffi ciently lower the oil – water interfacial
tension to form MEs, nor are they of the right molecular structure (i.e., HLB) to
act as cosolvents. To overcome such a barrier, cosurfactant/cosolvent molecules are
added to further lower the interfacial tension between oil and water, fl uidize the
hydrocarbon region of the interfacial fi lm, and infl uence the curvature of the fi lm.
Typically small molecules (C3 – C8) with a polar head (hydroxyl or amine) group
that can diffuse between the bulk oil and water phase and the interfacial fi lm are
suitable candidates [11] .
All the abovementioned mechanisms are expected to facilitate the formation and
stabilization of ME systems.
5.10.4
PHARMACEUTICAL FORMULATION OF MICROEMULSIONS 773
PHARMACEUTICAL FORMULATION OF MICROEMULSIONS
5.10.4.1 Selection of Microemulsion Ingredients
Pharmaceutically acceptable ME systems are formulated using at least GRAS -
(generally regarded as safe) and preferably pharmaceutical - grade ingredients, that
is, ones already in use in pharmaceutical formulation and devoid of serious side
effects and toxicity in humans [12] . Nonionic and zwitterionic surfactants are among
the most commonly used ingredients to formulate pharmaceutical MEs while vegetable
oils, medium - and long - chain triglycerides, and esters of fatty acids are the
most commonly used oils [2] . Among the range of nonionic surfactants used are
sucrose esters [13] , polyoxyethylene alkyl ethers [14] , polyglycerol fatty acid esters
[15] , polyoxyethylene hydrogenated castor oil [16] , and sorbitan esters [17] . Furthermore,
systems formulated with zwitterionic phospholipids, particularly lecithin, have
been widely investigated because of their biocompatible nature [9, 18 – 22] .
The effect of the oily component on the phase behavior of o/w ME - forming
systems formulated with nonionic surfactants was reported [23] . The authors showed
that it is possible to formulate cosurfactant - free o/w ME systems suitable for use as
drug delivery vehicles using either polyoxyethylene surfactants or amine - N - oxide
surfactants. The major advantage of these ME systems is their ability to be diluted
without destroying their integrity; however both classes of surfactants were shown
to be sensitive to electrolytes.
The choice of cosurfactants to formulate pharmaceutically acceptable MEs is
challenging as most of the cosurfactants investigated in fundamental ME research
cannot be used for the development of pharmaceutically acceptable systems due to
biocompatibility considerations. Among the pharmaceutically acceptable cosurfactants
are ethanol [24] , medium - chain mono - and diglycerides [25 – 28] , 1,2 - alkanediols
[29, 30] and sucrose – ethanol combinations [31] , alkyl monoglucosides, and
geraniol [32] . Kahlweit et al. [29, 30] reported on the usefulness of certain 1,2 -
alkanediol cosurfactants as nontoxic substitutes to the physiologically incompatible
short - and medium - chain alcohols. They suggested the possible use of these components
for the formulation of nontoxic ME systems.