The Art and Science of Microencapsulation

The Art and Science of
Microencapsulation
Spanning almost half a century, the
Institute's development of microencapsulation processes and devices
keeps pace with client needs
14
Technology Today · June 1995
o o
0
by John Franjione, Ph .D ., and
Niraj Vasishtha, Ph.D .
The rotating centrifugal head
microencapsulation device shown
here was designed at SwRI in the
1960s. Core and shell liquids are
fed separately to the head; the
materials are then distributed to an
array of coaxial nozzles located on
the face of the head. Core-in-shell
capsules are produced from each
nozzle. Though a two-nozzle head
is pictured, as many as 50 nozzles
have been incorporated into a single rotating head. A variety of
materials have been encapsulated
using this process, including pharmaceuticals, agrochemicals, flavor
oils, living cells, adhesives, vitamins, and water.
hat do scratch-and-sniff perfume advertisements, laundry detergents, baking
mixes, and aspirin have in common? Each
product relies on microencapsulation to
provide its unique attributes. Microencapsulation is a process by which tiny
parcels of a gas, liquid, or solid active
ingredient are packaged within a second
material for the purpose of shielding the
active ingredient from the surrounding
environment. These capsules, which
range in size from one micron (one-thousandth of a millimeter) to seven millimeters, release their contents at a later time
by means appropriate to the application.
There are four typical mechanisms
by which the core material is released
from a microcapsule - mechanical rupture of the capsule wall, dissolution of the
wall, melting of the wall, and diffusion
through the wall. Less common release
mechanisms include ablation (slow erosion of the shell) and biodegradation.
Two well-known applications of
microencapsulated products rely on
mechanical rupture of the shell to release
the core contents. Scratch-and-sniff perfume advertisements work because tiny
perfume-filled microcapsules are coated
onto the magazine page. When scratched,
the shell wall ruptures, releasing the perfume. Carbonless copy paper utilizes the
same release mechanism. Small capsules,
1-20 microns in diameter, coat the underside of the top sheet of paper. The capsules contain a dye precursor - a clear
chemical that by itself will not put a mark
on the lower page, but darkens in color
when exposed to an acidic component
(such as attapulgite clay or phenolic
resin). This acidic component coats the top
of the lower sheet. When subjected to the
high local pressure beneath a pen point,
the capsules break, the two reactants mix,
and the copy appears on the lower sheet.
Another area where microencapsulation has been widely applied is in the
detergent industry. Some powder detergents contain protein reactive enzymes
such as protease, used in removing blood
stains. The enzymes are encapsulated in a
water-soluble polymer, such as polyethylene glycol, for aesthetic reasons and safe
handling purposes. Released upon shell
dissolution in the washing machine, the
enzymes attack the blood protein, thereby
helping to remove the blood stain.
Many packaged baking mixes include
encapsulated ingredients to delay chemical reactions until proper temperatures
are reached) Sodium bicarbonate is a
baking ingredient that reacts with food
acids to produce leavening agents, which
give baked goods their volume and lightness of texture. To delay and control the
leavening process, the sodium bicarbonate is encapsulated in a fat, which is solid
at room temperature but melts at a temperature of about 125° F. Release of the
core material is delayed until the proper
temperature is reached.
Microencapsulated products in the
pharmaceutical industry are common,
particularly when sustained release of a
medication is required. Aspirin provides
effective relief for fever, inflammation,
and arthritis, but direct doses of aspirin
can cause peptic ulcers and bleeding.
The drug is therefore sometimes
encapsulated in ethyl cellulose or
hydroxypropyl methylcellulose
and starch (aspirin tablets are
formed by pressing together
collections of these microcapsules). Rather than being released all at once, the aspirin
diffuses through the shell
in a slow, sustained dose.
15
Or. John Franjione is a postdoctoral Fellow at SwRI, where
his work has focused on the fluid
mechanics of the Institute's coextrusion microencapsulation
processes. He has extensive experience in the application of chaotic
dynamic systems theory to fluid
mixing problems. Or. Niraj
Vasishtha, a research engineer
specializing in chemical encapsulation techniques and release characteristics modeling, is involved in
a number of industrial and pharmaceutical projects, including the
development of methods to encapsulate pancreatic islets, a treatment for type I diabetes. Both work
in the Microencapsulation and
Process Research Section in the
Chemistry and Chemical
Engineering Division.
Microencapsulation is a growing field
that is finding application in many technological disciplines. A wide range of core
m aterials in addition to those listed above
have been encapsulated. These include
adhesives, agrochemicals, catalysts, living
cells, flavor oils, pharmaceuticals, vitamins, and water. There are many advantages to microencapsulation. Liquids can
be handled as solids, odor or taste can be
effectively masked in a food product, core
substances can be protected from the deleterious effects of the surrounding environment, toxic materials can be safely
handled , and drug delivery can be controlled and targeted. In most microcapsules, the shell materials are u sually
organic polymers; however, waxes and
fats have also been used, particularly in
food and drug applications where the
shell must meet u.s. Food and Drug
Administration specifications.
Microencapsulation as an Art
The preparation of a microencapsulated product involves a number of steps.
First, the need for microencapsulation,
whether it is to enhance the quality of an
16
existing product or to develop an entirely
new product, must be identified. Next, a
shell m a terial that provides the desired
release characteristics must be chosen.
Finally, a process to prepare the microcapsules must be selected.
This procedure is something of an
ar t, as Asajo Kondo asserts in Micro-
capsule Processing and Technology:
Microencapsulation is like the
work of a clothing designer. He
selects the pattern, cuts the
cloth, and sews the garment in
due consideration of the desires
and age of his customer, plus the
locale and climate where the
garment is to be worn. By analogy, in microencapsulation, capsules are designed and prepared
to meet all the requirements in
due consideration of the properties of the core material, intended use of the product, and
the environment of storage ... 2
Certain techniques and processes
contribute to this view of microencap-
Technology Today · June 1995
sulation as an art, primarily
because of the broad range of
scientific and engineering disciplines they encompa ss, as
well as the interconnectivity of
these disciplines.
Consider, for example, the
process called complex coacervation. Conceived in the 1930's
by colloid chemist Barrett Green
at the National Cash Register Corporation, it was the first process u sed to
make microcapsules for carbonless copy
paper.3 In complex coacervation, the substance to be encapsulated is first dispersed as tiny droplets in an aqueous
solution of a polymer such as gelatin. For
this emulsification process to be successful, the core material must be immiscible
in the aqueous phase. Miscibility is
assessed using physical chemistry and
therm odynamics. The emulsification is
usually achieved by mechanical agitation,
and the size distribution of the droplets is
governed by fluid dynamics.
A second water soluble polymer,
such as gum arabic, is then added to this
emulsion. After mixing, dilute acetic acid
is added to adjust the pH. Though both
polymers are soluble in water, addition of
the acetic acid results in the spontaneou s
formation of two incompatible liquid
phases. One phase, called the coacervate,
has relatively high concentrations of the
two polymers; the other phase, called the
supernatant, has low polymer concentrations. The concentrations of the polymers
in these two phases, and the pH at which
phase separation occurs, are governed by
specific properties of physical chemistry,
thermodynamics, and polymer chemistry.
If the materials are properly chosen,
the coacervate preferentially adsorbs onto
the surface of the dispersed core droplets,
forming microcapsules. Again, physical
chemistry and thermodynamics dictate
whether the coacervate adsorbs onto the
core material. The capsule shells are usually hardened first by cooling (heat transfer), and then by chemical reaction
through the addition of a cross-linking
agent such as formaldehyde (polymer
chemistry). The release characteristics of
the microcapsules are governed by materials science (mechanical), heat transport
(thermal release), and mass diffusion (diffusion through the wall).
Each aspect of this process is highly
dependent upon the others. For example,
the thermodynamics of the phase separation affects the composition of the shell
material, and this affects the ability of the
shell to wet the core phase, as well as
determining the barrier properties and
release characteristics.
Despite extensive research to fully
comprehend the coacervation process, it
has been almost impossible to study the
influence of each of these factors on an
individual basis. Furthermore, answers to
some questions - how fast should the pH
be lowered, how can agglomeration and
formation of free coacervates be avoided,
what are the effects of rapid cooling remain qualitative.
Considering the difficult questions
involved, the interconnectivity of different process elements, and the fact that
there are hundreds of encapsulation
process variations, it is little wonder
that microencapsulation is sometimes
regarded as an art. However, at SwRI,
researchers are trying to gain a better scientific understanding of the different
aspects of chemical and physical encapsulation processes, to more efficiently tailor
results to client needs.
Microencapsulation as a Science
Because no single encapsulation
process can produce the complete range
of products desired by potential users,
SwRI has continually expanded its
microencapsulation capabilities. In the
last 45 years, the Institute has developed
and refined a number of microencapsulation processes and devices.
One encapsulation technology used
at SwRI for a number of commercial
applications is the co-extrusion process. 4,5,6 Liquid core and shell materials
are pumped through concentric orifices,
with the core material flowing in the central orifice, and the shell material flowing
through the outer annulus. A compound
drop composed of a droplet of core fluid
encased by a layer of shell fluid forms .
The shell is then hardened by appropriate means; for example, by chemical
crosslin king in the case of polymers,
cooling in the case of fats or waxes, or
solvent evaporation.
Though it sounds deceptively simple,
co-extrusion capsule formation is quite
complicated. The size of the capsules
produced, as well as the quantity of core
material contained within each capsule,
depends on the physical properties of the
•
--
(a)
(b)
(0)
(d)
Technology Today' June 1995
fluids (densities, viscosities, and interfacial tensions), the processing conditions
(flowrates and temperatures), the geometry of the nozzle (diameters of the inner
and outer orifices), and the amplitude and
frequency of small vibrational disturbances (natural or imposed) present in the
system. Because there are so many variables, and because it is often difficult to
vary one without affecting another (for
example, changing the viscosity of the
shell fluid changes the interfacial tension
between it and the surrounding fluid, and
between it and the core fluid) , it is
extremely difficult to isolate the influence
of the individual factors. For this reason,
co-extrusion processes are designed, and
operating conditions determined, on a
case-by-case basis. Nevertheless, the principles of momentum conservation and
fluid mechanics relevant to capsule formation processes provide a framework on
which Institute researchers are developing
a fundamental understanding of capsule
formation by co-extrusion.
Depending on the flowrates of core
and shell materials, capsules are formed in
one of two modes: drip or jet. In drip mode,
core and shell liquids flow out of the concentric orifices at a low rate, and a compound drop begins to form at the nozzle
tip. As is the case with a slowly dripping
faucet, surface tension prevents the compound drop from immediately separating
from the orifice. However, once it is large
enough, the weight of the drop overcomes
the cohesive force of surface tension, and
the drop falls from the nozzle. As long as
the fluid flowrates and temperatures
remain constant, this process can produce
uniform sized, but fairly large, capsules.
The drip mode co-extrusion process
was first used at SwRI in 1949 to encapsulate gasoline for more stable storage, and
it is still being used. In 1988, Institute scientists devised a means to encapsulate
cells that aid in bone fracture healing? The
objective was to find a means to deliver
osteoprogenitor cells to the fracture site.
Sodium alginate, a known biocompatible
This series of images illustrates the effect of
imposing vibration on the breakup of a compound liquid jet. Without vibration (a), jet
breakup is random - capsules contain
many droplets of core material. When frequency is increased (b), the jet breaks up
into a series of large drops, alternating with
a series of smaller satellite drops. A frequency range can be found (c) such that a
stream of monodisperse compound drops is
produced; however, beyond a particular frequency (d), vibration has no effect.
17
Qmax, axisymmetric
Flowrate
As the total flowrate from the nozzle is increased from zero, the mode of compound drop
formation changes. At low flowrates, surface tension (which causes fluid to adhere to the
nozzle tip) dominates, and compound drops form one at a time. At some higher flowrate,
the inertial force of the fluid exceeds the surface tension force, and a compound drop forms.
This flowrate can be related to the nozzle diameter (0), the fluid surface tension (a), and
density (p) 12:
Q . t=~ ( aD
Je
2
p
3) 1/2
Compound drops form due to axisymmetric breakup of this jet. At a still higher flowrate, the
mode of jet breakup changes from axisymmetric to sinuous. The maximum volumetric
flowrate for axisymmetric breakup is a function of the previously mentioned quantities, as
well as the fluid viscosity13:
D 1.14~O . 72aO . 14
Q max axisymmetric
,
= 81n -----'.--po.a6
If flowrate is further increased, breakup occurs via atomization at the nozzle tip, and multinuclear compound drops are formed. Capsule size is quite small, but size distribution is
much broader. For the majority of applications, it is most desirable that drops are formed
via axisymmetric breakup. Production rates are higher than they are in drip mode, and drop
size distribution can be controlled using vibration.
substance, w as used as the sh ell m a terial.
The core and shell solution s were d elivered to a nozzle (a small diam eter syringe
needle) at a rate of 0.5 milliliter p er minute.
A stream of air was forced to flow around
the n eedle tip to accelera te the ra te of
d etachment of cap sules from the nozzle
tip . Th is resulted in the formation of
sm aller cap su les (approximately 700
micron s) compared to the size of those
form ed w ithout the air stream. The liquid
cap sules were collected in an aqu eou s
solution of calcium chloride. In this solu -
18
tion, a chemical reaction occurs, in w hich
the w ater soluble sodium algina te is converted to an insoluble calcium alginate gel.
Although drip m od e produces uniform capsules, the production rate is quite
low (approximately 20 to 30 cap sules p er
minute). Increased output can only be realized by u sing multiple nozzles. H owever,
the cost of pumping and capsule collection
equipmen t often prohibits scale-up of d rip
m ode encap sulation processes.
If the fl owrates of th e core and sh ell
materials are in creased beyond som e criti-
Technology Today · June 1995
cal value, cap sules do n o t take sh ap e at
the n ozzle tip. Ra ther, a comp ound je t,
con sisting of a jet of core fluid encased by
a sheath of shell fluid, is formed. The critical flowrate is the flow ra te at w hich the
inertial force associa ted w ith the velocity of the fl owing fluid just exceed s the
surface ten sion forc e, w hich tends to
cau se fluid to adhere to the n ozzle tip.
A fluid jet is not a s table geom e tric
configu ra tion . Because of su rface tension, infinitesimally sm all p erturbation s
in the jet's shap e (from tha t of a perfectly
sm ooth cylinder) tend to grow, u n til
their size is comparable to the jet diameter. Th e compound jet breaks up into
compound drople ts, wi th diam eters
rou ghly twice those of the compound jet .
The jet m od e of opera tion is applied
in three d ifferent d evices a t SwRI - the
s ta tionary n ozzle, the ro tating centrifugal h ead, and the submerged n ozzle.
The sta tionary nozzle and rota ting head
are similar in tha t both extrude capsules
into the air. However, in the ro ta ting
cen trifugal h ead , m ultiple nozzles (anyw h ere fro m 2 to 50) are m ounted on a
ro ta ting sh aft; thus, capsules a re sp atially distributed, resulting in fewer capsule agglom era tion p roblem s. The
submerged n ozzle is u sed to prepare
large cap sules (greater than one millimeter in d iam e ter) in w hich the shell is
solidified by cooling (air d oes n ot p rovide effective heat tran sfer for su ch large
p articles). Th e compound fluid je t is
extruded into a flow ing liquid carrier
s tream a nd breakup occurs in this liq u id . Aft er the compound drops h ave
formed , the tempera ture of the liquid
carrier fluid is reduced, and the capsule
shells solid ify.
Centrifugal extrusion has been u sed
a t SwRI to prep a re en cap sulated
re tinoids, (vitamin A analogs) for u se in
lab oratory animal d iets.s En cap sulation
was necessary becau se retin oids decom p ose on exposure to heat, light, and oxygen. A corn oil solution of retinoids was
en cap sulated in an aqueous gela tin solution and the cap sules collected on a bed
of s tarch , w hich absorbed much of th e
water from the cap sule shell. Head speed
and m a terial feed rates were adjusted to
obtain capsules in the desired size range.
In a project for the U.S. Bu reau of
Mines, Institute scientists used th e submerged n ozzle to prep are wa ter-filled
wax capsules for a fast-settin g gyp sum
grouting cement for r einforcing b olt
adhesion in coal min e roofs.9 Th e wa ter-
filled capsules, one to two
millimeters in diameter,
are mixed with dry gypsum , and the mixture is
placed in a thin-walled tube.
The tube is then placed in
the bolt hole. When the
bolt is inserted into the
hole, the capsules in the
tube are crushed. This
releases the water, and the
cement rapidly solidifies.
The capsules were
prepared b y extruding a
water /wax compound jet
into a conduit through
which hot water flowed.
Both the core and carrier
water temperatures must
be high enou gh so that
the jet d oes not solidify before it breaks
into compound drops. Once the drops are
formed, the stream is cooled using a double pipe heat exchanger.
The Future of Co-extrusion Processes:
Vibration-Assisted Jet Breakup
Though a jet mode of encapsulation
yields much higher production rates
than a drip mode, capsule uniformity is
not as consistent. Standard deviations of
capsule sizes are typically 35 to 50 percent of the mean cap sule diameter. For
many applications, a narrow size distribution, with standard devia tions one to
two p ercent of the m ean capsule diameter, is desired . Narrow size distributions
are of grea t advantage in applica tion s
requiring controlled release. With the
ability to control wall thickness and fill
quantities, release characteristics of
microcapsules can be precisely tailored
to specific applications.
As discussed, the fluid jet breaks up
because of disturbances on the jet surface . The size distribution of the compound drops is related to the frequencies
of these disturbances. If the frequency of
the disturbance imparted to the jet can be
precisely controlled, then a droplet
stream with a very narrow size distribution can be produced.
Controlled disturbances can be imparted to jet streams b y mechanically
shaking the entire nozzle assembly at the
desired frequency. However, simply
imposing the desired fr equ ency is n ot
sufficient. Forced brea kup of a compound fluid jet is a complex process, and
the geometry of the compound drops
produced is dependent on the imposed
frequency.
Digitized image
:
•
Under internal research and
development at SwRI is a
novel machine vision-based
control system that allows inflight capsule inspection.
Process input variables, such
as f/owrate, temperature, and
vibrational frequency and
amplitude, will be manipulated
via a feedback control loop to
obtain desired capsule size
and sphericity.
(j)
• • • • • • • • •fIII
Feedback
control
~
Video camera
As disturbances on the jet surface
grow, bulges and necks are formed in the
jet. Sometimes, the neck of fluid which
connects drops just before breakup is not
pulled back into one of the droplets, but
pinches off at both ends, forming w hat is
term ed a satellite droplet. Clearly, if
mono disperse drops are d esired, satellite
formation is unwanted. The mechanisms
of, and m eans to suppress, satellite formation are not well understood and are active
areas of fluid mechanics research.1 0,1l
Even less is known about compound
fluid jets, which exhibit much more complicated behavior. Because there are two
fluid jets, the growth rate of disturbance
at the shell/ air interface can differ from
tha t a t the core/shell fluid interface.
Satellite droplets can be formed in the
shell fluid, resulting in a bimodal distribution of capsule sizes, or in the core
fluid, resulting in cap sules which have
multiple cores.
Summary
Because of the multitude of factors
that must be take n into account when
designing and preparing microcapsules,
it is likely that microencapsulation w ill
remain, to some extent, an art. However,
this does not preclude a scientific understanding of microencapsula tion processes. Researchers at SwRI are working
to better understand the physical mechanisms governing compound fluid jet
breakup and satellite formation, to design
more efficient co-extrusion microencapsulation processes. These processes will
be capable of producing capsules with
narrower size distributions and more uniform shell thicknesses at higher production rates . •:.
Technology Today. June 1995
References
1. Dziezak, J.D., "Microencapsulation and Encapsulated Ingredients," Food Techllology, 42,1988, pp.
136-151.
2. Kondo, A., Microcapsule Processillg and
Techllology, Marcel Dekker, Inc., New York, 1979.
3. Fanger, G.O., "What Good Are Microcapsules?"
CltemTech, 4,1974, pp. 397-405.
4. Somerville, G.R., "Multi orifice Centrifuga l
Head," U.S. Patent 3,015,128, 1960.
5. Somerville, G.R., "Sloped Head," U.s. Paten t
3,310,612,1967.
6. Somerville, G.R., "Method for Mass Producing
Small Spherical Particles," U.s. Patent 3,389,194,
1968.
7. Schlameus, H.W., W.C Fox, D.J. Mangold, J.D.
Trevino, G.T. Moore, T. Aufdemorte, J. Poser, D .
Carnes, "Preparation and Eva lu ation of Encapsulated Cells and Bone Growth Factors," Proceedings, 1990 International Symposium on
Controlled Release of Bioactive Materials, p. 369.
8. Mangold, D.J., N.F. Swynnerton, CW. Lew,
"Encapsulation of Retinoids for Administration in
Laboratory Diets," Final Report to th e Na tional
Cancer Institute, Contract NOI-CP-85601, March
1982.
9. Schuetze, CE., "Development of Water Capsules," Final Report to the U.s. Bureau of Mines,
Contract H0272042, 1978.
10. Scheller, B.L., and D.W. Bousfield, "Viscous Jet
Breakup: Nonsinusoidal Disturbances," Chemica l
Engineering COII/IIIUllicatiollS, 107, 1991, pp. 35-53.
11. Tjahjadi, M., H .A. Stone, and J.M. Ottino,
"Satellite and Subsatellite Formation in Capillary
Breakup," journal of Fluid Mechanics, 243,1992, p p.
297-317.
12. Scheele, G.F., and B.J. Meister, "Drop Formation
at Low Velocities in Liquid-Liquid Systems. Part
II. Prediction of Jetting Velocity," American Institute
of Chemical Ellgineers journal, 14, 1968, pp. 15-1 9.
13. Grant, R.P., and S. Middleman, "Newtonian Jet
Stability," American Institllte of Chemical Engineers
journal, 12, 1966, pp. 669-678.
19