Oil-Water Emulsions: Particle Size Distributions

from Elastic Light Scattering Data

MICHAEL HOFER, JOSEF SCHURZ, AND O T T O GLATTER

Institut ffir Physikalische Chemic, Universitgit Graz, Heinrichstrafle 28, A-8010 Graz, Austria
Received July 16, 1987; accepted February 3, 1988

Particle size distributions are important quality criteria for pharmaceutical emulsions. Fat emulsions
for intravenous administration should have a typical particle size of a few hundred nanometers and not
overshoot an upper size limit of 2 urn. Particles with a higher diameter, suspected to cause adverse
reactions (emboli), can be found in a phase contrast microscope. Our method uses elastic light scattering,
i.e., the angular dependent scattering intensity to size particles in the range of 100 nm up to several
micrometers. The advantage of this method compared with quasi-elastic light scattering is the higher
resolution due to a higher information content of the experiment (much lower condition numbers of
the matrix). It takes into account the actual relative refractive index and uses the Lorenz-Mie theory as
a basis of the inversion procedure. This yields accurate number and intensity distributions, defined as
the relative number of particles and the relative scattering intensity in the interval R and R + dR. Since
the scattering intensity is roughly proportional to the sixth power of the radius, larger particles can be
found in the intensity distribution even if their number is in the ppm range. We can therefore supply
the producer with two important and well-defined kinds of information: (a) the number distribution,
which provides the parameters of the particles like mean, standard deviation, and skewness; (b) the
intensity distribution, which is a very sensitive control for undesired large particles. © 1989Academic
Press, Inc.

1. INTRODUCTION m o s t cases the particle size d i s t r i b u t i o n o f the

T h e d i s p e r s i o n o f o n e i m m i s c i b l e liquid in
a n o t h e r liquid in the f o r m o f small d r o p l e t s is
called a n emulsion. W i t h the c o m p o n e n t s wa-
ter a n d oil two types o f e m u l s i o n are possible:
oil-water (O/W) and water-oil (W/O)
emulsions. W a t e r is the o u t e r or the i n n e r
phase, respectively.
E m u l s i o n s have b e c o m e increasingly i m -
p o r t a n t in m e d i c i n e , chemistry, p h a r m a c y ,
a n d m a n y o t h e r fields. F a t emulsions, for ex-
a m p l e , are e m p l o y e d in m e d i c i n e for p a r e n -
teral n u t r i t i o n o r to t r a n s p o r t water-insoluble
drugs, t h e r e b y a v o i d i n g u n d e s i r e d s e c o n d a r y
effects f r o m solvents or dissolving i n t e r m e d i -
aries. T h e y are i m p o r t a n t for special poly-
m e r i z a t i o n processes in c h e m i s t r y o r for sew-
age purification in e n v i r o n m e n t a l sciences.
Physiologists are interested in the b e h a v i o r o f
c h y l o m i c r a (which are n a t u r a l "fat-emulsions"
in the b l o o d ) u n d e r different conditions. In
dispersed phase is a n i m p o r t a n t p a r a m e t e r for
the c o n t r o l a n d / o r the stability o f the e m u l -
sion.
Since oil particles in water have a relative
refractive i n d e x m o f a b o u t 1.1 o r greater a n d
since these particles are n e a r l y perfect spheres,
optical m e t h o d s for accurate particle sizing
should use the L o r e n z - M i e t h e o r y (1, 2) as
the basis o f the i n t e r p r e t a t i o n procedure.
T h e m o s t c o m m o n optical techniques for
particle sizing in the m i c r o m e t e r regime are:
( a ) Quasi-elastic light scattering, also re-
ferred to as "laser D o p p l e r - s h i f t " or " p h o t o n
c o r r e l a t i o n " spectroscopy. C o n v e n t i o n a l de-
tection at a scattering angle o f 90 ° sizes par-
ticles f r o m s o m e n a n o m e t e r s u p to several m i -
crometers. T h e m e t h o d gives q u i c k results b u t
with p o o r resolution ( 3 ) .
( b ) F r a u n h o f e r diffraction, which evaluates
particle size d i s t r i b u t i o n s f r o m the forward

147
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Journal of Colloid and Interface Science, Vol. 127, No. 1, January 1989 All rights of reproduction in any form reserved.
148 HOFER, SCHURZ, AND GLATTER
scattered intensity. This method works well in
the size range of several micrometers up to the
millimeter regime, although relatively large
errors occur for particles smaller than about
5 ~tm if their contrast is not high enough (m
< 1.3 ) because of anomalous diffraction (4).
(c) Microscopy, which is used to detect
particles greater than several micrometers.
However, some special techniques such as
video-enhanced microscopy can be used to
size particles down to several hundred nano-
meters.
Besides these optical techniques, other
powerful methods of particle sizing are in use.
Let us briefly sketch four of the most impor-
tant ones:
(a) Centrifugation methods (such as the
Joyce-Loebl disk centrifuge with optical de-
tector) are used to size particles in the range
of several micrometers down to less than 0.1
/~m (5).
(b) The Coulter counter sizes particles by
measuring the change in resistance of a
charged orifice caused by the presence of non-
conducting particles. It is suitable for exam-
ining particles in the range of 1 to about 20
/~m (6).
(c) X-ray or neutron small angle scattering
can be employed to size particles from several
nanometers up to about 100 nm (7).
(d) Field-flow fractionation techniques are
used to obtain high resolution from less than
100 nm up to about 1/~m (8, 9).
The method described below uses elastic
light scattering, i.e., the angle-dependent scat-
tering intensity for particle sizing in the range
of about 0.1 /~m up to several micrometers
with high resolution. The Lorenz-Mie theory
is used as basis of the data inversion. The
method has the great advantage that very ac-
curate size distributions are obtained and that
it is applicable to an arbitrary relative refractive
index m in the preresonant Mie region, which
nevertheless must be known a priori. In the
following, independent and single scattering
is always assumed.
Journalof ColloidandInterfaceScience,Vol. 127, No. 1, January 1989
II. THEORY
Although a full description of the method
can be found in (10), we briefly review the
most important features.
We are able to calculate size distributions
from polydisperse systems if all particles have
the same refractive index and the same shape
but have different sizes defined by one size pa-
rameter R. A simultaneous determination of
size and shape of polydisperse samples is not
possible; the shape of the particles must be
assumed or known from other experiments.
We have already published a method for de-
termining such shapes from elastic light scat-
tering data for homogeneous and inhomoge-
neous, spherical and nonspherical particles
(11, 12). The above restrictions should be re-
membered although they are of little impor-
tance in the case of emulsions where all par-
ticles are nearly perfect spheres constituted by
the same material. Three size distributions are
commonly used:
(1) The number distribution Dn (R), giving
the number of particles in the size range of R
and R + d R .
(2) The mass or volume distribution
Dm(R), which is the mass or volume in the
interval R and R + d R .
(3) The intensity distribution Di(R), de-
fining the scattered intensity at zero angle
originating from the size interval R and R
+ dR.
The angle-dependent scattering intensity
from all particles l ( h ) is related to the above
distributions by the integrals
I(h) = Dn(R)ck(h, m, R ) d R [1]
fO °°
z(h)
= Dm(R)dp(h, m , R)4)(O, m, R ) - I / 2 d R
~0 °°
[21
I(h)
= Di(R)rb(h, m, R)49(O, m , R ) - ~ d R ,
fO °°
[31
 P A R T I C L E SIZE
where q~(h, m, R) represents the scattering
function of a particle with size R and refractive
index m. For convenience, the scattering angle
0 has been replaced in Eqs. [1]-[3 ] by the
wavelength-independent angular variable h,
which is
41r
h = ~ sin 0/2. [4]
R is the characteristic dimension of the par-
ticle, i.e., the radius for spherical scatterers. In
the Rayleigh-Debye-Gans approximation
(27rX-1R(m - 1) ~ 1) the three size distri-
butions are related by
Di(R) = R3Dm(R) = R6Dn(R). [51
Starting from the Rayleigh-Debye region
(small scattering objects with low contrast),
deviations of 4(0, m, R) from R 6 with in-
creasing size and refractive index clearly show
the Mie contributions to the scattering func-
tion (13).
It is impossible to solve Eqs. [ 1]- [ 3 ] ana-
lytically because no general analytical expres-
sion for 4(h, m, R) in the Lorenz-Mie theory
exists. Therefore, numerical methods must be
applied to solve Eqs. [ 1]- [ 3 ] to obtain the de-
sired particle size distribution. Discussion of
the mathematical details of the solution pro-
cedure (indirect transformation method) can
be found in (7, 10). It was necessary to modify
the method due to the fact that the Lorenz-
Mie scattering functions should be used to ap-
proximate the measured data instead of the
Rayleigh-Debye functions generated inter-
nally by the program.
For the generation of the Mie scattering
functions we have used the T-matrix algo-
rithms kindly sent to us by Professor P. W.
Barber. Since these programs can handle
spherical and spheroidal, homogeneous and
inhomogeneous scattering objects (14-19)
they are not optimized for the calculations of
scattering functions of spheres. Nevertheless,
since we have already performed many cal-
culations with this program package, which
proved to be accurate and "easy to handle"
even for persons not involved in the "kernel"
149
of electromagnetic theory, we continued to use
it for the generation of a large array of scat-
tering functions of homogeneous spheres. This
array contains functions starting from R
-- 12.5 nm up to R = 1050 nm (increment:
12.5 n m ) f o r m = 1.001, 1.05, 1.075, 1.1, 1.15,
1.2, 1.25, and 1.3. These functions are used
to fit the measured scattering data with the
indirect transformation method.
The method would allow use of a spherical
core-shell model to take into account the dif-
ferent refractive index of the detergent layer
on the surface. This layer is very thin com-
pared with the overall dimensions of the drop-
let and cannot be resolved by light scattering
experiments. This fact supports the use of ho-
mogeneous spheres.
We have tested the method using simulated
polydispersity profiles under various condi-
tions (10). Some emulsions of the present se-
ries have been investigated with other tech-
niques (quasi-elastic light scattering, micros-
copy, Fraunhofer diffraction, and Coulter
counter). These methods gave similar overall
shapes of the polydispersity profiles but were
not capable of the high resolution of the elastic
light scattering technique.
The resolution of our method is the same
as the resolution for Rayleigh-Debye scatter-
ing experiments (7, 10). Sharp peaks with a
size ratio down to 1:1.2 can be resolved. The
precision necessary for such a resolution is in
the order of several percentage points. All our
experimental data were below this limit.
To show the capabilities and the limitations
of our method under experimental conditions
we shall take as an example fat emulsions for
parenteral nutrition and focus our attention
on it in the following.
III. STABILITY OF FAT EMULSIONS
Emulsions are thermodynamically unstable
systems. They can be stabilized by emulsifiers,
which create barriers to the coalescence of
droplets by reducing the interracial tension
between two immiscible liquids because they
possess hydrophilic and hydrophobic regions
within the same molecule.
Journal of Colloid and Interface Science, Vol. 127,No. 1, January 1989
150
Some pure phospholipids, especially phos-
phatidylcholine, form neither good mechani-
cal nor good electrical barriers to droplet co-
alescence. One therefore utilizes egg or soy
lecithin together with ionic lipids (e.g., phos-
phatidylserine) for the stabilization of com-
mercial fat emulsions. Ionic lipids not only
increase the surface potential but also produce
complex interfacial films with phosphatidyl-
choline, which results in a liquid crystalline
gel structure at the interface (20-22).
In contrast to this, certain additives like
dextrose or electrolytes reduce the zeta poten-
tial considerably, leading to more unstable
systems (23).
The physical stability of emulsions and the
presence or absence of aggregation have im-
portant clinical consequences. Emulsions
containing droplets exceeding 6 # m in diam-
eter are known to cause adverse reactions,
particularly embolism in the lungs (24, 25).
Therefore, in Europe, fat emulsions for intra-
venous administration are not allowed to
overshoot an upper size limit of 5 #m. More-
over, it has been noticed that aggregation,
creaming, and storage capacity are strongly
dependent on the mean diameter of the sample
as well as on the presence of a small amount
of micrometer-sized particles. Consequently,
accurate determination of particle size distri-
bution is very helpful in the refinement of
production processes and in stability evalua-
tion and thus leads to higher security for the
patient.
IV. EXPERIMENTAL PROCEDURES
A. Experimental Setup
The experimental setup consists of a FICA
50 light scattering photometer (Sofica Co.,
France) which has been modified in order to
allow precise measurements of scattering an-
gles down to about 12 °. The instrument was
also equipped with additional electronic de-
vices for precise time integration and the pos-
sibility of transferring data automatically to a
computer via a standard serial interface (RS
232C). A detailed description of these im-
Journalof Colloidand InterfaceScience,Vol. 127, No. 1, January 1989
HOFER, SCHURZ, AND GLATTER
provements and of the primary data handling
can be found in (26).
All scattering curves were measured with
this instrument in the angular range of 12
~< 0 ~< 120 ° (0.003 ~< h ~< 0.026) at scattering
angles in three subdomains: 18 values were
recorded from 12 to 30 ° , 12 from 30 to 60 ° ,
and 14 from 60 to 120 ° in an equidistant h-
spacing. This is necessary in order to allow for
the solution of Eqs. [ 1] - [ 3 ] with the indirect
transformation technique. At each scattering
angle 100 intensity values (integration time
= 0.2 s/value) were recorded and the weighted
mean intensity was calculated. As statistical
control of the averaging process we used the
x-square and the F test (27). The precision of
our final data shown in Section V is in the
range of 0.5-3%.
FICA light scattering cuvettes are made of
crown glass. The minimum sample volume is
about 2 ml. To avoid contributions due to re-
flections the inner wall of the cuvette is made
conical (see Fig. 1).
C1 --A!
GFt--~....... A2
GF'2--~
C2--~--A3
GC--
--F1
- F2
-
C3--
D2
~ - - L SC
FIG. 1. Apparatusforthe purificationofwaterto produce
solvent free from dust and air-bubbles.
 PARTICLE SIZE
Inversion procedures for obtaining the size
distributions were performed on a UNIVAC
1100 / 81 computer, using the modified indi-
rect transformation technique. All polydis-
perse profiles are calculated up to a scattering
particle diameter of 2100 nm. The method is
not restricted to this relatively low value but
further extension would imply the measure-
ment of the scattering function at scattering
angles lower than 12 ° , which is not possible
with the present instrument. A new elastic light
scattering goniometer is under develop-
ment now.
B. Sample and Solvent Preparation
The emulsions contain water, Soja oil (20
wt%), Lecithine (1.2%), Glycerine (2.5%),
and NaOH to adjust the pH. They are pro-
duced with the usual technical procedure; i.e.,
Glycerine and water are mixed and heated to
the right temperature, then mixed with Leci-
thine and NaOH. This mixture is dispersed
and homogenized after the addition of the oil,
diluted to the right concentration of the oil,
and finally homogenized again in two steps.
According to the sampling theorem of the
Fourier transformation the smallest h-value
(hmin) defines roughly the maximum dimen-
sion, which can be evaluated from the scat-
tering function (see, for example, (28, 29)).
Therefore, if we try to investigate large particles
(of several micrometers), we should be able
to measure the scattering function starting
from a scattering angle of at least 10 °.
The measured scattering function Im~ is the
sum of the scattering from the particles Ip and
the solvent Is. The contribution of the particles
decreases approximately with h -4 whereas a
pure solvent ideally scatters light independent
of the scattering angle 0. At high 0 the two
quantities Ip and Is can therefore approach the
same order of magnitude. The subtraction (Ip
+ Is) - Is then introduces large errors iflp and
Is are not measured with high accuracy.
On the other hand, dust particles and micro
air bubbles either in the sample or in the sol-
vent cause relatively large errors in the poly-
dispersity analyses because of the strong scat-
151
tering intensity due to the high contrast (m
= 0.75 for air in water). Errors at low angles
are more critical than those at high scattering
angles since they influence the extrapolation
of the scattering curve to 0 = 0. This part of
the scattering function contains almost all the
information about the maximum dimension
found in the sample, and hence, these errors
lead to a wrong polydispersity profile for large
particles. It is therefore necessary to prepare
solvent and sample under dust-free conditions
without introducing air bubbles into the so-
lution. This procedure is usually fairly tricky;
it is still one of the main problems when elastic
light scattering measurements at small angles
should be performed. In the following we de-
scribe an apparatus which enables the pro-
duction of sufficiently purified water.
Water can prove to be a somewhat insidious
solvent in elastic light scattering experiments.
It has the ability to trap a n d / o r generate air
bubbles randomly. We have verified this be-
havior in a series of quasi-elastic light scatter-
ing experiments. With such an experiment it
is possible to determine the hydrodynamic ra-
dius of scatterers in solution in about 5 min
(30). Two cleaned and dried cuvettes were
filled with purified water and observed over 5
days. At the beginning, both samples showed
small impurities in the size range of about half
a micrometer, although the last filter of the
purification column had a pore size of 200
nm. During the time of observation, in the
first sample the size of the air bubbles increased
to about 4 ~m, whereas in the second sample,
the hydrodynamic radius fluctuated in the vi-
cinity of 1 #m. We have tried to improve the
reproducibility but without success.
We therefore started to eliminate step by
step all parts which could introduce impurities
and finally developed a closed system that
yields the desired results. A schematic diagram
of this apparatus is shown in Fig. 1: First, water
from the piping is taken and distilled (D 1) di-
rectly into a drop bottle (DB). This drop bottle
is then disconnected from the column and
stored in a vacuum drying oven and evacuated
down to 3 mbar. At this low pressure all air
Journal of Colloid and Interface Science, VoL 127, No. 1, January 1989
 152 HOFER, SCHURZ, AND GLATTER

bubbles will vanish. The drop bottle will be (~20% w/w) was highly diluted (1:106). This
attached to the purification column and closed dilution shortens the stability of the samples
with a plug containing a filter of pore size 50 considerably. While the stock solution has a
nm. The cock (C 1) will be slowly opened now stability of several months, the stability of the
and water passes through two glass frits (GF1, diluted samples reduces to 1-2 days. This sta-
GF2) of pore sizes <40 #m and < 16 #m, re- bility was checked by repeating the measure-
spectively. This is managed in such a way that ment at low scattering angles. Unstable prep-
no water drops can be formed which would-- arations were rejected and the sample was
when falling--trap air bubbles. prepared once again.
Cock C2 controls the amount of water in There is no direct evidence that the size dis-
the graduated cylinder (GC). This cylinder is tribution is completely unchanged during the
directly connected with two filter holders, dilution procedure. For energetical reasons,
which are made of polycarbonate (F1, F2). however, it is impossible for the size of the oil
The membrane filter in the first holder has a droplets in the emulsion to be decreased by
pore size of 450 nm, the second a pore size of dilution. Any increase in size corresponds with
50 nm (regenerated cellulose, Sartorius, FRG). a decrease in stability. Only stable solutions
All inlets for pressure equalization (A 1, A2, were used in the experiments. The original
and A3) are closed with the same 50-nm samples were analyzed by phase contrast mi-
membrane filters in a polycarbonate filter croscopy. Since this method is not able to give
holder. Back pressure due to F1 and F2 will accurate polydispersity profiles it can be used
be overcome simply by increasing the height only to check for very large particles and for
of the water in the graduate cylinder (GC) to a rough estimate of the mean diameter of the
obtain a pressure of about 10 mbar. Thus, the oil droplets. At lower concentrations (dilution
water flows directly into the second distilling factor 100-1000), quasi-elastic light scattering
apparatus (D2), which is made of glass with was used to check for changes. Within the res-
no connecting pieces. The water (about 50 ml) olution capabilities of the above methods, no
in the 250-ml glass flask will be heated by change in polydispersity profiles was observed.
means of a heating mantle whereby the tem- For precise evaluation of the size distribu-
perature is kept at 90°C to avoid boiling. It tion it is necessary to know the ratio m of the
slowly evaporates and flows down into the light refractive indices of the oil phase and of water
scattering cell (LSC) along the wall to prevent in the emulsion. Determination of the indices
generation of drops. of the separated phases was done at the factory
The apparatus contains no glass joints. All before the emulsification process. The ratio m
connections are made of high-quality silicon was 1.107 _ 0.005. An error of 0.01 in m
tubing. C1, C2, and C3 are Teflon cocks so would not cause essential errors in the results.
that particles due to attrition and the need to We checked the refractive index of the oil
use grease may be avoided. phase after induced creaming in our labora-
This apparatus provides water sufficiently tory. Perfect agreement was found.
purified that it no longer has the capability of
trapping air bubbles. The water will now be V. RESULTS
so clean that even at a scattering angle of 15 o With elastic light scattering, we have inves-
it is impossible to measure a correlation func- tigated more than 100 samples of fat emulsions
tion in a quasi-elastic light scattering experi- for parenteral nutrition, using commercially
ment. This ensures that no scattering particles available, aged samples as well test prepa-
of appreciable size are present in the solvent. rations from Leopold & Co. (Graz, Austria)
Water prepared in this way was used to di- prepared with the aim of further improving
lute all samples to obtain sufficiently accurate the quality of the final emulsions for clin-
scattering data for Is and lp. The stock solution ical use.
Journal of Colloid and Interface Science, Vol. 127, No. 1, January 1989
 PARTICLE SIZE 153

We discuss three examples from these test Z, ~ BL ,46

v I . B L 48
preparations, denoted by BL 46, BL 48, and
BL 51. In addition, we discuss one represen-
tative example from the bulk of commercially
available emulsions (SA 1) together with an
aged sample of the same producer (SA 2).
Figure 2 shows the measured scattering
curve of the three test preparations BL 46, BL
0 I I I
48, and BL 51 (circles), the fit (full line), and 30O 600 900 1200
the extrapolation to zero scattering angle R CnmJ

(dashed line). They have been plotted in the FIG. 3. Number distributions calculated via indirect
same logarithmic scaling in order to show transformation method from experimentaldata shown in
clearly the differences. BL 46 and BL 51 are Fig. 2. There are no significant deviations of mean and
very similar. In contrast to this, BL 48 shows skewness between the three samples.
a strong increase in scattering intensity in the
innermost part of the scattering curve. Since
of all distributions is small, indicating a good
large particles show a c o n s i d e r a b l e f o c u s i n g ef-
preparation. However, BL 51 is the best prep-
f e c t on the light--which means that they scat-
aration in the sense of monodispersity,
ter very efficiently to small scattering angles--
whereas it is difficult to recognize any differ-
BL 48 is suspected to have large oil droplets
ences between BL 46 and BL 48. No large par-
in the emulsion. Is it possible to recognize
ticles can be seen in this representation of the
them in a n u m b e r distribution?
scattering data although the innermost part of
Figure 3 depicts the n u m b e r distributions
the scattering curve of BL 48 (h ~< 0.01 or 0
D ~ ( R ) of BL 46, BL 48, and BL 51 evaluated
40 ° ) shows this strong increase in intensity
via the indirect transformation method. The
(see Fig. 2). This means that only a few large
mean of all three samples is very similar and
particles are present in sample BL 48.
lies in the vicinity of 150 nm. The skewness
The computed intensity distributions of BL
46, BL 48, and BL 51 are shown in Fig. 4.
5.5 Although BL 48 and BL 46 behave similarly
in the n u m b e r distribution (see Fig. 3 ) it now
turns out that BL 48 contains some large par-
5.5

.E
5.5
BL 48

17(~\\ , \
z,.5
46 7/\i\
! l ,
~ 5 F I ',

3.5 48

51 of "-Y ,-",~ ,
o 300 600 900 12oo
2"50.0 0.01 0.02 0.03-- R Into]
," h [nm-']
FIG. 4. Intensity distributions computed from experi-
FIG. 2. Measured scattering intensities (O) and fit mental data (Fig. 2). BL 46 and BL 51 showa monomodal
(--) extrapolated to zero angle (---) of three differently behavior; BL 48 is stronglyaffectedby contributions from
prepared fat emulsions for parenteral nutrition (angular large particles. Note that the shoulder at R ~ 900 nm is
range: 12 ~<0 ~< 120° or 0.003 ~<h ~<0.260). due to the limit of the experimental setup.
Journal of Colloid and Interface Science, Vol. 127, No. 1, J a n u a ry 1989
154
titles. Their concentration is so low that it is
impossible to resolve them in the number dis-
tribution. However, their scattering power is
so high that they can be found easily in the
intensity distribution (Fig. 4). The shoulder
at R "~ 900 n m indicates the presence of oil
particles too large to be resolved with the pres-
ent experimental setup (0rain ~- 12°). The
method cannot give the exact size of these
largest particles, but their existance is indicated
by the shoulder. For better resolution at large
R-values (up to several micrometers) one must
go down to scattering angles below 12 °.
The very small negative part of BL 46 at R
"~ 900 nm is due to the fact that the indirect
transformation method does not impose ad-
ditional constraints such as nonnegativity on
the solution. However, we have found that the
quality of the solution of the inverse problem
can often be improved by the additional con-
straint of nonnegativity (31), which is a phys-
ically based one, since there are no negative
numbers of particles. This constraint avoids
oscillations around the abscissa without af-
fecting the resulting solution essentially. A se-
ries of tests must be performed before this
constraint is used in the standard evaluation
routine. The use of singular value decompo-
6.0 ,
6+0
~o
5,0
o in the region 300 ~ R ~< 500 nm. From the
2 scattering data in Fig. 5, two main features of
3.0
0.0 O.Ol 0102 0103
~. h Into-I]
FIG. 5. Scatteringdata (©) and fit (--) of commercially
available(SA 1) and aged sample (SA 2) of the same pro- coalescense, a process taking place in every fat
ducer.
J o u r n a l o f C o l l o i d a n d Interface Science, Vol. 127, No. 1, January 1989
HOFER, SCHURZ, AND GLATTER
to
5
i i
00 300 600 900
I
1200
b R [nrn]
FIG.6. Number distributionsevaluatedfrom scattering
data in Fig. 5 differjust slightlyfrom each other. The nar-
row shape of the distributions seems to indicate the good
quality of both samples.
sition (31) has not yet led to improved solu-
tions for our inverse problem.
Let us now focus our attention on com-
mercially available fat emulsions for parenteral
nutrition. We shall discuss one representative
example of an emulsion still in clinical use
(SA 1) and another that is aged and no longer
in clinical use (SA 2). For convenience, these
two examples come from the same producer.
Figure 5 gives the measured scattering
functions (circles), the fit of the indirect
transformation method to the data (full line),
and the extrapolation to zero angle (dashed
line). The only remarkable differences be-
tween these two scattering functions is the
slightly stronger falloff of SA 2 and a somewhat
different extrapolation to low scattering angles.
The number distribution in Fig. 6 shows
very narrow skewness of both samples with a
mean diameter in the vicinity of 120 n m in-
dicating a considerable monodisperse prepa-
ration. Up to R = 1050 nm no large particles
can be recognized in either SA 1 or SA 2, the
latter showing a small number of oil droplets
intensity distribution in Fig. 7 evaluated from
the aged sample SA 2 become obvious: first,
the shift of the maximum to higher R-values,
which can be interpreted in terms of droplet
emulsion; second, the rise of larger particles
 PARTICLE SIZE 155

lO Lan, K. H., and Ostrowsky, N., J. Chem. Phys.

82, 1551 (1985).
4. Jones, A. R., J. Phys. D. 10, 163 (1977).
5. Coil, H., and Searles, C. G., J. Colloid Interface Sci.
115, 121 (1987).
6. Groves, M. J., J. Dispersion Sci. Technol. 1, 97 (1980).
7. Glatter, O., J. Appl. Crystallogr. 13, 577 (1980).
8. Yang, F. J., Myers, M. N., and Giddings, J. C., J.
Colloid Interface Sci. 60, 574 (1977 ).
0 t 9. Yang, F.-S., Caldwell, K. D., and Giddings, J. C., J.
300 600 900 1200 Colloid Interface Sci. 92, 81 (1983 ).
-"- R [ n m ] 10. Glatter, O., and Hofer, M., J. Colloid Interface Sci.
122, 496 (1988).
1716. 7. Intensity distributions calculated from scattering
11. Glatter, O., Hofer, M., Jorde, Ch., and Eigner,
data in Fig. 5. The distribution of the aged sample (SA 2 )
W.-D., J. Colloid Interface Sci. 105, 577 ( 1985 ).
shows a shift to higher particle sizes with a relatively large
12. Glatter, O., and Hofer, M., J. Colloid Interface Sci.
number of oil droplets in the critical range for clinical
122, 484 (1988).
application. 13. Hofer, M., Thesis, University of Graz, 1987.
14. Barber, P. W., and Yeh, C.,Appl. Opt. 14, 2864 (1975).
15. Barber, P. W., IEEE Trans. Microwave Theory Tech.
(R > 900 nm) suspected to cause dangerous
MI-T-2S, 373 (1977).
adverse reactions like lung emboli when ad- 16. Barber, P. W., and Wang, D.-S,, AppL Opt. 17, 797
ministered intravenously. (1978).
The techniques described above can be use- 17. Wang, D.-S., and Barber, P. W., Appl. Opt. 18, 1190
fully applied to any kind of oil/water or water / (1979).
18. Wang, D.-S., Chen, C. H. H., Barber, P. W., and
oil emulsions provided that droplets do not
Wyatt, P. J., Appl. Opt. 18, 2672 (1979).
exceed several micrometers in size, which 19. Barber, P. W., Wang, D.-S., and Long, M. B., Appl.
would imply the measurement of the scatter- Opt. 20, 1121 (1981).
ing function at very small scattering angles (19 20. Ries, H. E., Matsumoto, M., Uyeda, N., and Suito,
< 5 °). One preferably uses Fraunhofer dif- E., in "Monolayers" (E. D. Goddard, Ed.), p. 286,
Advanced Chemistry Series, Vol. 144.
fraction methods (32) in the latter case.
21. Rydhag, L., and Wilton, I., J. Amer. Oil Chem. Soc.
Investigations using elastic light scattering 58, 830 (1981).
techniques in the Rayleigh or preresonant Mie 22. Becher, P., "Emulsions Theory and Practice." Rein-
regime are not restricted to simple polydis- hold, New York, 1965.
persity analyses. This kind of technique can 23. Black, C. D., and Popovich, N. G., Drug Intell. Clin.
Pharmacol. 15, 184 (1981).
also be used to study various features of emul-
24. Geyer, R. P., Watkin, D. M., Matthews, L. W., and
sion systems like stability properties or kinetics Store, J., Proc. Exp. Biol. 77, 872 (1951).
of droplet coalescence under different tem- 25. Fujita, T., Sumaya, T., and Yokohama, K., Eur. Surg.
perature, electrolyte, or additive concentra- Res. 3, 436 (1971).
tions. 26. Hofer, M., Diplomarbeit, University of Graz, 1984.
27. Brandt, S., "Statistical and Computational Methods
ACKNOWLEDGMENTS in Data Analysis." North-Holland, Amsterdam,
1970.
This work was supported by the ()sterreichischer Fonds 28. Bracewell, R., "Fourier Transform and Its Applica-
zur Frrderung der wissenschaftlichen Forschung. We thank tions." McGraw-Hill, New York, 1965.
Mrs. K. Schaupp and J. Kerbl from Leopold & Co, Graz, 29. Glatter, O., J. Appl. Crystallogr. 10, 415 (1977).
for generously providing the samples and for fruitful dis- 30. Pecora, R., "Dynamic Light Scattering." Plenum, New
cussions. We also thank Mrs. B. Miiller for drawing the York, 1985.
figures. 31. Lawson, C. L., and Hanson, R. J., "Solving Least
Squares Problems." Prentice-Hall, Englewood
REFERENCES Cliffs, NJ, 1974.
1. Lorenz, L., Videnskab. Selskab. Skrifter. 6, (i 890). 32. "Proceedings, International Symposium on 'Optical
2. Mie, G.,Ann. Phys. 25, 377 (1908). Particle Sizing: Theory and Practice,' Rouen,
3. Bertero, M., Brianzi, P., Pike, E. R., de Villers, G., 1987."

Journalof ColloidandInterfaceScience,VoL 127,No. 1,January1989