European Journal of Pharmaceutical Sciences 11 Suppl.

2 (2000) S93–S98
www.elsevier.nl / locate / ejps

Lipid formulations for oral administration of drugs: non-emulsifying,

self-emulsifying and ‘self-microemulsifying’ drug delivery systems
Colin W. Pouton*
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7 AY, UK
Received 14 July 2000; accepted 11 August 2000

Abstract

‘Lipid’ formulations for oral administration of drugs generally consist of a drug dissolved in a blend of two or more excipients, which
may be triglyceride oils, partial glycerides, surfactants or co-surfactants. The primary mechanism of action which leads to improved
bioavailability is usually avoidance, or partial avoidance, of the slow dissolution process which limits the bioavailability of hydrophobic
drugs from solid dosage forms. Ideally the formulation allows the drug to remain in a dissolved state throughout its transit through the
gastrointestinal tract. The availability of the drug for absorption can be enhanced by presentation of the drug as a solubilizate within a
colloidal dispersion. This objective can be achieved by formulation of the drug in a self-emulsifying system or alternatively by taking
advantage of the natural process of triglyceride digestion. In practice ‘lipid’ formulations range from pure oils, at one extreme, to blends
which contain a substantial proportion of hydrophilic surfactants or cosolvents. Knowledge of the efficiency of emulsification of these
formulations, the nature of the colloidal system formed by dispersion, their susceptibility to digestion, and the subsequent fate of the drug
is desirable for formulation. Yet the literature on this subject is limited, so this article represents part review and part commentary on
current status of lipid formulations. A simple classification system for lipid formulations, based on the polarity of the blend and reviewed
here, will help comparison of data between laboratories. Priorities for future work are discussed. More data is needed on the solubility of
drugs in various types of formulations, and in particular, on the relationship between the physical chemistry of the drug and its fate,
subsequent to dilution and digestion of the formulation in the lumen of the gastrointestinal tract. The mechanisms of action and practical
uses of each type of lipid formulation are discussed.  2000 Elsevier Science B.V. All rights reserved.

Keywords: Oral bioavailability; Hydrophobic drugs; Lipid drug delivery; Self-emulsification; Self-emulsifying drug delivery system; SEDDS

1. Introduction
In recent years several successful oral pharmaceutical
products have been marketed as lipid systems, notably
cyclosporin A (originally marketed as ‘SandimmuneE’ and
now as the improved product ‘NeoralE’) and the two HIV
protease inhibitors, ritonavir and saquinavir. Consequently,
there is now considerable interest in the potential of lipid
formulations for oral administration. It was not always so;
the potential of self-emulsifying drug delivery systems has
been evident for at least 15 years (Pouton, 1985a,b), and in
the earlier literature there were many references to the
beneficial effects of food or oils on bioavailability of
hydrophobic drugs (Humberstone and Charman, 1997).
Nevertheless a preference for solid dosage forms prevailed
until the case of cyclosporin A emerged, when it became
clear that its formulation with lipids or surfactants had
*Tel.: 144-1225-826-786; fax: 144-1225-826-114.
E-mail address: c.w.pouton@bath.ac.uk (C.W. Pouton).
been crucial to the success of the oral capsule product. The
literature on the mechanisms of action, optimisation and
performance of lipid formulations for oral administration is
relatively small. In particular there are very few reports of
systematic bioavailability studies in man. Considerable
growth can be anticipated over the next decade. In this
article I aim to describe the current status of lipid
formulations, and discuss aspects of their use which will
require further evaluation in the future.
The use of lipid systems has been reviewed on various
occasions. Prior to the emergence of self-emulsifying
systems, Armstrong and James (1980), reviewed the
release of drugs from lipids. Several useful reviews have
been published in recent years. Humberstone and Charman
(1997) reviewed the biopharmaceutical literature. Strate-
gies for formulation of self-emulsifying systems, and
efforts to understand their mechanisms of action, have
been reviewed by Constantinides (1995), Pouton (1997),
Craig et al. (2000) and Gershanik and Benita (2000). In
practice ‘lipid’ formulations are a diverse group of formu-

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S94 C.W. Pouton / European Journal of Pharmaceutical Sciences 11 Suppl. 2 (2000) S93 –S98
Table 1
Typical properties of Type I, II, IIIA and IIIB lipid formulations
Increasing hydrophilic content →
Type I
Typical composition (%)
Triglycerides or 100
mixed glycerides
Surfactants – 20–60
Hydrophilic – –
cosolvents
Particle size of Coarse
dispersion (nm)
Significance of aqueous Limited
dilution importance
Significance of Crucial
digestibility requirement
lations which have a wide range of properties. These result
from the blending of up to five classes of excipients;
ranging from pure triglyceride oils, through mixed
glycerides, lipophilic surfactants, hydrophilic surfactants
and water-soluble cosolvents. Table 1 describes one meth-
od of classifying different lipid formulations. Myself and
my research group use this classification system, which
was first described last year (Pouton, 1999), to aid
comparison of published data from other laboratories. The
virtues of each type of formulation are discussed below.
One general working hypothesis which can be applied to
the use of all lipid formulations, relates to their general
mechanism of action; that their advantage results from
their ability to ensure that the drug remains in solution
throughout its transit within the gastro-intestinal tract.
Stated another way, if the drug precipitates within the gut,
the dissolution form the crystalline form will result in
slower, more variable absorption. The significance of this
hypothesis in relation to formulation will be discussed
below.
2. Classification of lipid delivery systems
The simplest lipid products are those in which the drug
is dissolved in digestible oil, usually a vegetable oil or
medium chain triglyceride (fractionated coconut oil).
These are safe food substances, classed as GRAS (general-
ly regarded as safe) by regulatory agencies, and do not
present a toxicological risk to formulators. Although few
drugs have been formulated in this way, oil solution has
been the standard way of administering oil-soluble vita-
mins (A and D) for many years. Bioavailability from oil
solutions is likely to be very good because the triglycerides
are rapidly digested to free fatty acids and 2-mono-
glycerides, and these products are solubilised to form a
Type II Type IIIA Type IIIB
40–80 40–80 ,20
20–40 20–50
(HLB,12) (HLB.11) (HLB.11)
0–40 20–50
100–250 100–250 50–100
Solvent capacity Some loss of Significant phase
unaffected solvent capacity changes and potential
loss of solvent capacity
Not crucial but Not crucial but Not required
likely to occur may be inhibited and not likely to occur
colloidal dispersion within bile salt-lecithin mixed mi-
celles. A hydrophobic drug is also likely to be solubilised
in mixed micelles resulting in a reservoir of drug in
colloidal solution from which it can partition, allowing
efficient, passive (transcellular) absorption. The bioavail-
ability and plasma profile of a lipophilic 5a-reductase
inhibitor from an oil solution were equivalent to those
achieved using a self-emulsifying system (Loper et al.,
1996). Oil digestion by gastro-intestinal lipases has been
reviewed by Embleton and Pouton (1997), and the signifi-
cance of digestion in the context of drug bioavailability has
been discussed in more detail by MacGregor et al. (1997).
The low solvent capacity of triglycerides often prevents
formulation in oil, but oil solutions may be a realistic
option for potent drugs or for compounds with log P.4.
Solvent capacity for less hydrophobic drugs can be im-
proved by blending triglycerides with other oily excipients
which include mixed monoglycerides and diglycerides.
Since these are similar to the natural degradation products
of triglycerides (the difference being that their mono-
glyceride content is mostly 1-monoglyceride rather than
2-monoglyceride) they do not prevent efficient digestion.
As excipients with GRAS status they have the same
advantages as triglycerides, and are useful for blending
with triglycerides or for use as an alternative. Formulations
which comprise drug in solution in triglycerides and / or
mixed glycerides are classified here as ‘Type I’ (Table 1).
When an appropriate dose of the drug can be dissolved, a
Type I formulation may well be the system of choice, in
view of its simplicity and biocompatibility.
The inclusion of a lipophilic surfactant (HLB,12) may
improve the solvent capacity of the formulation, but this
approach has mainly been used to promote emulsification.
Under optimum conditions it is possible to formulate a
‘self-emulsifying drug delivery system’ (SEDDS) which
emulsifies in aqueous solutions under very gentle con-
 C.W. Pouton / European Journal of Pharmaceutical Sciences 11 Suppl. 2 (2000) S93 –S98
ditions of agitation, to result in a dispersion of colloidal
dimensions. If the surfactant is insufficiently hydrophilic to
dissolve and form micelles in aqueous solution, then it
exists itself as a dispersed phase, either with or separated
from the oily components. This type of formulation is
likely to retain its solvent capacity for the drug after
dispersion and is referred to as Type II (Table 1). The
distinguishing features of Type II systems are (a) efficient
self-emulsification and (b) absence of water-soluble com-
ponents. Formulation of Type II SEDDSs has been de-
scribed in detail elsewhere (Pouton, 1982, 1984, 1985a,b;
Wakerley et al., 1986a,b, 1987; Charman et al., 1992) and
reviewed recently (Pouton, 1997). Briefly, Type II systems
are best formulated with medium chain triglycerides and /
or mono or diglycerides, blended with ethoxylated oleate
esters with HLB values of approximately 11. As the
surfactant content in the blend is increased there is a
threshold at approximately 25% (w / w) surfactant beyond
which self-emulsification occurs. At high surfactant con-
centrations, greater than approximately 65% depending on
the materials, the progress of emulsification is compro-
mised by viscous liquid crystalline gels which form at the
oil–water interface. If homogenised these mixtures would
produce very stable emulsions, but they require energy to
break up the particles and in practice are not self-emulsify-
ing systems. Type II systems consisting of medium chain
triglycerides and polyoxyethylene-(25)-glyceryl trioleate
(Tagat TO) have been reported to produce particles as fine
as 100–250 nm by self-emulsification, depending on the
surfactant concentration (Wakerley et al., 1986a,b; Waker-
ley, 1989).
Hydrophilic surfactants (water soluble with HLB.12)
and / or water-soluble cosolvents have also been blended
with oils to produce self-emulsifying systems. When the
surfactant content is high (for example 40%, w / w, or
more) or co-solvents are included in addition to surfac-
tants, it is possible to produce very fine dispersions (,100
nm in diameter) under conditions of gentle agitation
(Constantinides, 1995; Constantinides and Scalart, 1997).
This approach was used for the reformulation of cyclos-
porin A as ‘Neoral’ (Vonderscher and Meinzer, 1994). The
motivation for using hydrophilic surfactants or water-solu-
ble cosolvents (such as propylene glycol, polyethylene
glycol, ethanol, etc.) may also be to increase the solvent
capacity of the formulation for drugs with intermediate
log P (2,log P,4). The distinction to be made between
these and Type II formulations is that the water-soluble
components will tend to part from the oil during disper-
sion, and become dissolved in the aqueous phase. The
result of this phase separation, which may in fact be the
driving force for emulsification by ‘diffusion and strand-
ing’, is likely to be loss of solvent capacity. The conse-
quence may be that the drug is partially precipitated when
the formulation disperses. The extent of precipitation will
depend on the physical chemistry of the drug and how
hydrophilic is the formulation. Formulations which include
S95
water-soluble components are referred to in Table 1 as
Type III formulations, and have been referred to as ‘self-
microemulsifying’ systems, due to the optical clarity which
can be achieved with Type III systems. As the risk of
precipitation is greater when the formulation contains a
higher proportion of hydrophilic components, Type III
formulations can be arbitrarily split into Type IIIA and
Type IIIB, to help identify very hydrophilic (Type IIIB)
formulations.
3. Biopharmaceutical issues and choice of formulation
3.1. Dose of drug
The optimum formulation for each drug will depend on
a number of considerations; on the required dose, on which
types of formulation have sufficient solvent capacity to
allow for formulation of a unit dose, and in particular on
the fate of the drug after these formulations have been
administered to the gut. In many instances the choice of
formulation will be limited by solvent capacity, and in
others the drug will not be sufficiently soluble in any lipid
formulations. Generally the most difficult drugs are those
which have limited solubility in both water and lipids
(typically with log P values of approximately 2). It is
unlikely that lipid formulation will be of value for such
drugs. In contrast, more hydrophobic drugs may permeate
lipid bilayers freely but dissolve very slowly in the lumen
of the gut. It has been common in the past for formulators
to be presented with the challenge of formulating a high-
dose oral product for a new hydrophobic drug, in circum-
stances when the dose has been estimated using the results
of early pre-clinical animal studies. Such studies may have
been conducted with an inadequate formulation, such as a
crude aqueous suspension, from which bioavailability is
poor. It these circumstances it is wise to anticipate that
bioavailability may be much greater from a lipid system,
which may allow pharmacological activity to be achieved
with a lower dose. This is particularly important for drugs
with high log P, when in the first instance the solvent
capacity of lipid formulations appear to fall short of the
required dose.
If the drug is potent and is sufficiently soluble in Type I,
Type II or Type III systems then a choice will need to be
made between these options. The most important consid-
eration should be to avoid precipitation of the drug (see
below), but a secondary consideration is whether or not
rapid absorption is desirable. Typically Type II or Type III
systems will undergo gastric emptying earlier and will be
in a colloidal state earlier than Type I systems. An
emulsifying system is likely to result in more rapid
absorption and higher peak concentrations of drug. If the
drug has a low therapeutic index this may be undesirable,
which argues in favour of a Type I formulation.
S96 C.W. Pouton / European Journal of Pharmaceutical Sciences 11 Suppl. 2 (2000) S93 –S98
3.2. Significance of droplet size
Tarr and Yalkowsky (1989) were able to demonstrate in
a gut perfusion experiment that emulsion droplet size
affected the rate of absorption of cyclosporin A. Absorp-
tion was more rapid from the finer of two emulsions,
though the emulsions compared were both relatively
coarse. The situation is very different when a small volume
of a lipid formulation is administered in a capsule. The
contents of the capsule will be emptied into the digestive
environment of the upper small intestine, so that the most
important factor may not be the size of the particles in the
initial dispersion, but rather their susceptibility to digestion
and / or solubilization by mixed micelles of bile salts and
phospholipids. One consequence of reducing the oil con-
tent and including surfactants and cosolvents is that the
droplets become less susceptible to digestion (see below).
This means that self-emulsifying systems are dependent on
the initial emulsification process to produce a colloidal
dispersion. It is assumed that the droplet size should be as
fine as possible, and there is some evidence that this
assumption holds in the case of cyclosporin A. The drug
was more available from the ‘Neoral’ formulation than the
earlier ‘Sandimmune’ formulation, which was a coarsely
emulsifying system (Mueller et al., 1994a). One possible
explanation for this observation may be that the coarse
emulsion produced by the ‘SandimmuneE’ formulation
could not be reduced to colloidal dimensions, due to
limited digestion.
Type IIIB formulations generally produce the finest
dispersions, due to their high content of water-soluble
solubilizing agents (Constantinides, 1995). However, we
have been able to produce dispersions with particle diame-
ters lower than 100 nm using Type II systems (Hasan and
Pouton, unpublished data). Whether there is a significant
difference in bioavailability between systems which
produce droplet sizes of 250 versus 100 nm, remains to be
investigated.
3.3. The risk of precipitation
Consider the example of a hydrophobic drug dissolved
in a pure cosolvent such as polyethylene glycol or pro-
pylene glycol. When the formulation is added to water the
solvent capacity of the mixture falls approximately loga-
rithmically as the formulation is diluted into water. The
result is precipitation of the drug. It is much more difficult
to predict the fate of the drug on dispersion of a typical
Type IIIA lipid formulation; perhaps consisting of a drug
dissolved in 30% medium chain triglycerides, 40% mixed
partial glycerides, and 30% hydrophilic surfactant. The
hydrophilic surfactant will be substantially separated from
the oily components, forming a micellar solution in the
continuous phase. The question is does this lower the
overall solvent capacity for the drug? That will depend on
the log P of the drug, and to what extent the surfactant was
contributing to its solubilization within the formulation. At
present there are no established techniques available to
help formulators assess the risk of precipitation. Equilib-
rium solubility measurements can be carried out and this
will help anticipate potential cases of precipitation in the
gut. However crystallisation could be slow in the solubiliz-
ing and colloidal, stabilizing environment of the gut. Our
preliminary studies at Bath have shown that crystallisation
from some Type III formulations can take up to 5 days to
reach equilibrium, and that the drug can remain in a
super-saturated state for up to 24 h after the initial
emulsification event (Hasan and Pouton, unpublished
results). It could be argued that such products are not likely
to cause precipitation of the drug in the gut before the drug
is absorbed, and indeed that super-saturation could actually
enhance absorption by increasing the thermodynamic
activity of the drug. There is a clear need for practical
methods to predict the fate of drugs after the dispersion of
lipid systems in the gastro-intestinal tract.
3.4. Role of lipolysis and solubilization in bile
Digestion of dietary triglyceride in the small intestine is
very rapid, and many other non-ionic esters, such as mixed
glycerides and surfactants will be substrates for pancreatic
lipase (Embleton and Pouton, 1997). Digestion of formula-
tions will inevitably have a profound effect on the state of
dispersion of the lipid formulation, and the fate of the drug
(MacGregor et al., 1997). Fortunately the liberation of free
fatty acid during lipolysis can be titrated using NaOH in a
pH stat, allowing quantitative data to be obtained relating
to the kinetics of digestion. The location of the drug can be
assayed in various fractions after ultracentrifugation of the
products of digestion, which allows investigation of the
likely fate of the drug after lipolysis. One possibility is that
the drug will be solubilized in mixed micelles of bile salts
and phospholipids. The capacity for solubilization of
mixed micelles is dependent on the physical properties of
the drug, but this can be studied relatively easily as a
preformulation exercise (Naylor et al., 1995; Solomon et
al., 1996a; Mithani et al., 1996). The natural process of
digestion offers the possibility that very hydrophobic drugs
could be taken up into the lymphatic system by partition-
ing into chylomicrons in the mesentery (Porter and Char-
man, 1997). This is expected to be a mechanism of
absorption for drugs with log P values greater than 6, and
has been demonstrated to be crucial for the absorption of
the anti-malarial compound halofantrine (Porter et al.,
1996).
It is possible that digestion of a lipid formulation could
reduce the solubility of the drug in the gut lumen, which
would result in precipitation of the drug and a decrease in
the absorption rate. More research needs to be carried out
to establish which drugs are precipitated on digestion. For
 C.W. Pouton / European Journal of Pharmaceutical Sciences 11 Suppl. 2 (2000) S93 –S98
such compounds Type II or Type III systems might be
preferable, since the presence of surfactants can inhibit
digestion of the oil within the formulation (Solomon et al.,
1996b; MacGregor et al., 1997). Type III systems such as
‘Neoral’ have been shown to act independently of bile,
which suggests that they are not necessarily digested
before the drug is absorbed (Mueller et al., 1994b; Trull et
al., 1995; Kahan et al., 1995).
4. Future prospects
In conclusion, more attention needs to be paid to the
characteristics of various lipid formulations available, so
that guidelines and experimental methods can be estab-
lished that allow identification of candidate formulations at
an early stage. Methods need to be sought for tracking the
solubilization state of the drug in vivo, and there is a need
for in vitro methods for predicting the dynamic changes,
which are expected to take place in the gut. Attention to
the physical and chemical stability of drugs within lipid
systems, and the interactions of lipid systems with the
components of capsule shells will also be required. Whilst
these present challenges there is great potential in the use
of lipid formulations. The priority for future research
should be to conduct human bioavailability studies, and to
conduct more basic studies on the mechanisms of action of
this fascinating and diverse group of formulations.
References
Armstrong, N.A., James, K.C., 1980. Drug release from lipid based
dosage forms. Part 2. Int. J. Pharm. 6, 195–204.
Charman, S.A., Charman, W.N., Rogge, M.C., Wilson, T.D., Dutko, F.J.,
Pouton, C.W., 1992. Self-emulsifying systems; formulation and bio-
logical evaluation of an investigative lipophilic compound. Pharm.
Res. 9, 87–94.
Constantinides, P.P., 1995. Lipid microemulsions for improving drug
dissolution and oral absorption: physical and biopharmaceutical as-
pects. Pharm. Res. 12, 1561–1572.
Constantinides, P.P., Scalart, J.P., 1997. Formulation and physical charac-
terization of water-in-oil microemulsions containing long- versus
medium-chain glycerides. Int. J. Pharm. 158, 57–64.
Craig, D.Q.M., Patel, M.J., Ashford, M., 2000. Administration of
emulsions to the gastrointestinal tract. In: Nielloud, F., Marti-Mestres,
G. (Eds.), Pharmaceutical Emulsions and Suspensions. Marcel Dekker,
New York pp. 323-360.
Embleton, J.K., Pouton, C.W., 1997. Structure and activity of gastro-
intestinal lipases. Adv. Drug Delivery Rev. 25, 15–32.
Gershanik, T., Benita, S., 2000. Self-dispersing lipid formulations for
improving oral absorption of lipophilic drugs. Eur. J. Pharm. Bio-
pharm. 50, 179–188.
Humberstone, A.J., Charman, W.N., 1997. Lipid-based vehicles for the
oral delivery of poorly water soluble drugs. Adv. Drug Delivery Rev.
25, 103–128.
Kahan, B.D., Dunn, J., Fitts, C., Van Buren, D., Wombolt, D., Pollak, R.,
Carson, R., Alexander, J.W., Choc, M., Wong, R., 1995. Reduced inter-
and intrasubject variability in cyclosporine pharmacokinetics in renal
S97
transplant recipients treated with a microemulsion formulation in
conjunction with fasting, low-fat meals, or high-fat meals. Trans-
plantation 59, 505–511.
Loper, A.E., Booth, S., Clarke, A., Olah, T.V., McLoughlin, D.A., Novak,
L.B., Hettrick, L.A., Storey, D.E., 1996. Equivalence of a self-emul-
sifying drug delivery system (SEDDS) and soybean oil for oral
delivery of a 5a-reductase inhibitor in rhesus monkeys. In: Couvreur,
P., Duchene, D., Kalles, I. (Eds.), Proc. Eur. Symp. Formulation of
Poorly-available Drugs for Oral Absorption. Editions de Sante, Paris,
pp. 369–372, ISBN 2-86411-096-2.
MacGregor, K.J., Embleton, J.K., Perry, E.A., Lacy, J., Seager, H.,
Solomon, L., Pouton, C.W., 1997. Lipolysis of oily formulations in the
gastro-intestinal tract. Adv. Drug Delivery Rev. 25, 33–46.
Mithani, S.D., Bakatselou, V., TenHoor, C.N., Dressman, J., 1996.
Estimation of the increase in solubility as a function of bile salt
concentration. Pharm. Res. 13, 163–167.
Mueller, E.A., Kovarik, J.M., Van Bree, J.B., Tetzloff, W., Kutz, K.,
1994a. Improved dose linearity of cyclosporin pharmacokinetics from
a microemulsion formulation. Pharm. Res. 11, 301–304.
Mueller, E.A., Kovarik, J.M., Van Bree, J.B., Grevel, J., Kutz, K., 1994b.
Influence of a fat rich meal on the pharmacokinetics of a new oral
formulation of cyclosporin in a cross-over comparison with the market
formulation. Pharm. Res. 11, 151–155.
Naylor, L.J., Bakatselou, V., Rodriguez-Hornedo, N., Weiner, N.D.,
Dressman, J., 1995. Dissolution of steroids in bile salt solutions is
modified by the presence of lecithin. Eur. J. Pharm. Biopharm. 41,
346–353.
Porter, C.J.H., Charman, W.N., 1997. Uptake of drugs into the intestinal
lymphatics after oral administration. Adv. Drug Delivery Rev. 25,
71–90.
Porter, C.J.H., Charman, S.A., Charman, W.N., 1996. Lymphatic transport
of halofantrine in the triple-cannulated anaesthetized rat model; effect
of lipid vehicle digestion. J. Pharm. Sci. 85, 351–356.
Pouton, C.W., 1982. Self-emulsifying systems for drug delivery. PhD
Thesis, University of London.
Pouton, C.W., 1984. Assessment of the efficiency of self-emulsifying
formulations. J. Pharm. Pharmacol. 36, 51P.
Pouton, C.W., 1985a. Effects of the inclusion of a model drug on the
performance of self-emulsifying formulations. J. Pharm. Pharmacol.
37, 1P.
Pouton, C.W., 1985b. Self-emulsifying drug delivery systems: assessment
of the efficiency of emulsification. Int. J. Pharm. 27, 335–348.
Pouton, C.W., 1997. Formulation of self-emulsifying systems. Adv. Drug
Delivery Rev. 25, 47–58.
Pouton, C.W., 1999. Key issues when formulating with lipids. Bull. Tech.
Gattefosse 92, 41–50.
Solomon, L.J., Embleton, J.K., Pouton, C.W., 1996a. Inhibition of
lipolysis of medium-chain triglycerides by non-ionic surfactants: a
structure activity study. In: Couvreur, P., Duchene, D., Kalles, I.
(Eds.), Proc. Eur. Symp. Formulation of Poorly-available Drugs for
Oral Absorption. Editions de Sante, Paris, pp. 437–440, ISBN 2-
86411-096-2.
Solomon, L.J., Embleton, J.K., Pouton, C.W., 1996b. Solubilisation of
steroidal compounds by mixed bile salt-lecithin micelles. In: Couvreur,
P., Duchene, D., Kalles, I. (Eds.), Proc. Eur. Symp. Formulation of
Poorly-available Drugs for Oral Absorption. Editions de Sante, Paris,
pp. 219–222. ISBN 2-86411-096-2
Tarr, B.D., Yalkowsky, S.H., 1989. Enhanced intestinal absorption of
cyclosporin in rats through the reduction of emulsion droplet size.
Pharm. Res. 6, 40–43.
Trull, A.K., Tan, K.K.C., Tan, L., Alexander, G.J.M., Jamieson, N.V.,
1995. Absorption of cyclosporin from conventional and new mi-
croemuslion oral formulations in liver transplant recipients with
external biliary diversion. Br. J. Clin. Pharmacol. 39, 627–631.
Vonderscher, J., Meinzer, A., 1994. Rationale for the development of
Sandimmune Neoral. Transplant Proc. 26, 2925–2927.
S98 C.W. Pouton / European Journal of Pharmaceutical Sciences 11 Suppl. 2 (2000) S93 –S98

Wakerley, M.G., 1989. Self-emulsifying drug delivery systems based on
non-ionic surfactant-oil mixtures. PhD thesis, University of Bath.
Wakerly, M.G., Pouton, C.W., Meakin, B.J., Morton, F.S., 1986a. Self-
emulsification of vegetable oil-nonionic surfactant mixture: a proposed
mechanism of action. Am. Chem. Soc. Symp. Ser. 311, 242–255.
Wakerly, M.G., Pouton, C.W., Meakin, B.J., Morton, F.S., 1986b. The
effect of surfactant HLB on the self-emulsifying efficiency of nonionic
surfactant-vegetable oil mixtures. J. Pharm. Pharmacol. 38, 2P.
Wakerly, M.G., Pouton, C.W., Meakin, B.J., 1987. Evaluation of the
self-emulsifying performance of a non-ionic surfactant-vegetable oil
mixture. J. Pharm. Pharmacol. 39, 6P.