Applications of Emulsion

Emulsions have been used as drug carriers for more than a century. Today, several
types of emulsions exist and are used for a variety of applications from solubilizing
drugs to controlled release. Emulsions can be delivered by oral, topical, and parenteral
routes. When administered by oral route, O/W emulsions can efficiently
improve the oral absorption and bioavailiability of poorly water-soluble drugs.
Improved absorption was seen for drugs such as griseofulvin, theophylline, and
phenytoin (Carrigan and Bates 1973; Gagnon and Dawson 1968; Diamond 1970).

Fig. 1.3 Schematic diagram of membrane emulsification process. The dispersed phase (i.e. oil)
is forced through the membrane by applying pressure. The droplets formed at the membrane
surface are detached by the continuous phase flowing across the membrane
Oil phase under applied pressure Membrane Continuous phase Fine O/W emulsion

Oral administration of a W/O emulsion containing ovalbumin, a model antigen has
been shown to be more efficient in enhancing the immunogenic response than that
of ovalbumin in saline (Masuda et al. 2003).

For parenteral drug delivery, both W/O and O/W emulsions have been investigated
but O/W emulsions are predominantly used. W/O emulsions are easy to
prepare; have good physical stability; and are easily injectable because of their low
viscosity (Bjerregaard et al. 1999a). They have the potential for sustained release
of hydrophilic drugs, since the surfactant layer acts as a release barrier for drugs
present in the aqueous phase (Davis et al. 1985). In addition, the release properties
from a W/O emulsion can be controlled within certain limits by adjusting parameters
such as droplet size, osmotic gradients, and volume fraction of the dispersed
phase (Bjerregaard et al. 1999b). In vivo sustained release of aprotoin, a 58 amino
acid polypeptide, from W/O emulsion has been demonstrated in mice and rabbits
(Bjerregaard et al. 2001a, b). O/W or lipid emulsions are used for parenteral nutrition
therapy, as well as for therapeutic agents. In lipid emulsions, the oil phase is
typically a glyceride.
Oils mostly used in lipid emulsions are soybean oil, cottonseed
oil, safflower oil, and medium-chain triglycerides.

Egg phospholipids are themost commonly used emulsifying agents in lipid emulsions.
Lipid emulsions offer numerous advantages as parenteral drug carriers such as solubilization of highly
lipophilic drugs, stabilization of labile drugs against hydrolysis or oxidation, sustained
release, and drug targeting. They are biocompatible, biodegradable, and
reduce drug side effects by avoiding direct contact of the drug with the body fluid
and tissues. Lipid emulsions have been used in parenteral nutrition for more than
four decades for delivering fatty acids to patients who cannot eat or metabolize food
properly.

Examples of marketed formulations are Intralipid, Lipofundin, and
Liposyn. Lipid emulsions have been investigated for a number of drugs to treat
various disease conditions such as rhizoxin (Stella et al. 1988) and taxol (Tarr et al.
1987) for cancer, physostigmine (Rubinstein et al. 1991) for Alzheimer’s disease,
and prostaglandine E1 (Mizushima et al. 1983) for thrombosis therapy. Lipid emulsions
of diazepam, propofol, and etomidate are commercially available.

The use of lipid emulsions as ophthalmic vehicles has been explored in the last
few years. Lipid emulsions are excellent ocular delivery vehicles as already proved
by Restasis®. Restasis® contains cyclosporine A indicated for increased tear production
in patients with keratoconjunctivitis sicca. Drugs such as indomethacin (Klang
et al. 2000), piroxicam (Klang et al. 1999), and difluprednate (Yamaguchi et al.
2005) have been investigated for ophthalmic lipid emulsions.

Double emulsions are excellent systems for the encapsulation of bioactive
compounds. The presence of a reservoir phase inside droplets of another phase
can be used to sustain release of active compounds, to protect sensitive molecules
from external phase, taste masking, immobilization of enzymes, and for
the enhancement of enteral and dermal absorption.

The most common double emulsions used are of W/O/W type to entrap water-soluble drugs.
Potential applications of double emulsions have been comprehensively reviewed by Khan
et al. (2006).