j. microencapsulation, 2001, vol. 18, no.

6, 801±809

Morphology and structure of microcapsules prepared by

interfacial polycondensation of methylene bis(phenyl
isocyanate) with hexamethylene diamine

E. JABBARI
Laboratory of Biomaterials and Controlled Delivery Systems for Bioactive
Journal of Microencapsulation Downloaded from informahealthcare.com by University of Windsor on 07/07/14

Agents, Department of Biomedical Engineering, Amirkabir University of

Technology, Tehran, Iran

(Received 30 August 2000; revised 14 December 2000; accepted 23 March 2001 )

Polyurea microcapsules containing 2-chloro-N-(2,6-diethylphenyl)-N-(meth-

oxymethyl) acetamide as the active agent were prepared by the method of
interfacial polycondensation with methylene bis(phenyl isocyanate) as the
multifunctional isocyanate, hexamethylene diamine as the diamine, and anionic
sodium lignin sulphonate (SLS) as the emulsifying agent. The internal
structure and morphology of the microcapsules were examined with transmis-
sion electron microscopy. The microcapsules had a micro-reservoir structure in
which the wall extended well into the core and the active agent was
accommodated by the micro-reservoirs, distributed uniformly throughout the
entire volume of a microcapsule. Based on the observed morphology,
For personal use only.

permeability of the water soluble monomer in the polyurea ®lm and its
solubility in the oil phase have a signi®cant e€ ect on the morphology and
microstructure of the microcapsules. The multivalent salt, calcium chloride,
plays a signi®cant role in stabilizing the microcapsule structure, by interacting
with the anionic surfactant SLS, and physically crosslinks the SLS chains, by
interacting with the negatively charged carboxylic and phenolic groups, with
subsequent phase separation of the physically crosslinked chains to form a
concentrated gel phase. This gel phase encompasses the microcapsule, increases
the stability, and modi®es its release behaviour.

Keywords: Microencapsulation, interfacial polycondensation, methylene bis-

(phenyl isocyanate), hexamethylene diamine, microstructure.

Introduction

Microencapsulation is used in a variety of applications as a trapping technology

to protect the active agent from the undesired conditions of the environment and to
prolong the release of the active agent (Arshady and George 1993, Knauer and
Southgate 1997, Yu and Lee 1997, Zgoulli et al. 1999, Ho€ man et al. 2000, Okano
2000, Pedraz et al. 2000, Putman et al. 2000). One of the most important
applications of microencapsulation is in agriculture for encapsulating herbicides,
pesticides, and fertilizers to provide prolonged release for crop safety, reduce the
number of applications, reduce volatilization to the atmosphere, slow pesticide

* To whom correspondence should be addressed: ejabari@cic.aku.ac.ir

Journal of Microencapsulation ISSN 0265±2048 print/ISSN 1464±5246 online # 2001 Taylor & Francis Ltd
http://www.tandf.co.uk/journals
DOI: 10.1080/02652040110065396
 802 E. Jabbari

mobility and degradation in the soil, and reduce preferential transport of pesticides
(Levy et al. 1993, Schreiber et al. 1993, Luteri 1999).
Microcapsules and microspheres can be prepared by a variety of physical
and chemical methods. The technique used commercially for microencapsula-
tion of pesticides and herbicides is interfacial polycondensation (Nastke and
Neuenschwander 1999), in which the active agent is encapsulated within a poly-
urethane or polyurea shell (Chao 1993, Shukla et al. 1999). Characterization of the
structure and properties of microencapsulated pesticides prepared by the method
of interfacial polycondensation has been the subject of extensive research in the
past few decades. For example, Sibley and Fortin (1989) attempted to visually
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detect microencapsulated pesticides in the digestive content of aquatic inverte-

brates with selective staining, and found that SEM was the most suitable with
the smear method for sample preparation. Chao (1993) observed that, in the
presence of a ®xed amount of emulsi®er, sodium carboxy methyl cellulose was
better than methyl cellulose for synthesizing polyurea microcapsules in terms of
average particle size and particle size distribution.
Zhang et al. (1995) observed that the microcapsule diameter did not change
appreciably beyond 45 s of mixing time, for microcapsules prepared by the method
of interfacial polycondensation, and the initial membrane was not strong enough to
prevent the microcapsules from coalescing. Pearson and Williams (1985) observed
a gel layer around the droplets, such that this gel layer was swollen by the diol but
not by the polyfunctional isocyanate in interfacial polycondensation to form
For personal use only.

polyurethane microcapsules, and they proposed a core-shell model in which the

liquid active agent was surrounded by a polymeric wall.
Pense et al. (1994) studied the formation of benzalkonium chloride loaded
microencapsules by interfacial polycondensation with methylene bis(phenyl iso-
cyanate) as the isocyanate. They observed that carbon black, which was spread on
the aqueous side of the interface, was not included in the thickness of the
polymeric ®lm after recovering, which indicated that the microcapsule wall was
formed and grown in the organic phase. In another study, Ichikawa (1994)
observed that the glass transition temperature of polyurethane-urea microcapsules
without core material was higher than the microcapsules with core material, which
indicated that the core material plasticized the wall and the wall material was
amorphous. Shanta and Panduranga Rao (1993) observed that microcapsules
containing methylene bis(phenyl isocyanate) (MDI) were more porous as com-
pared to toluene diisocyanate (TDI) microspheres, and the release rate of
bromomethyl blue was faster with MDI as compared to TDI microspheres.
Polyurethane microspheres were also prepared (Jabbari and Khakpour 2000)
using the method of suspension polycondensation with MDI and polyethylene
glycol 400 as the multifunctional isocyanate and diol, respectively. The micro-
spheres were porous due to the formation of carbon dioxide by the reaction of
MDI with water, and the porosity was signi®cantly a€ ected by the concentration
of a chain extending agent due to the variations in the ratio of hard-to-soft
segments of the PU chains. Yadav et al. (1996) observed that a minimum wall
thickness was necessary in order to preserve the integrity of the microcapsules with
hexamethylene diisocyanate (HMDI) and hexamethylene diamine (HMDA) as the
two reacting monomers.
In general, the process of interfacial polycondensation is complex, and wall
formation is a€ ected by many variables such as the nature and composition of the
 Morphology and structure of microcapsules 803

two immiscible phases, the concentration of the reactants, physico-chemical

properties of the encapsulating agent, the partition coe cient of each reactant
between the two phases, chemical nature and concentration of the chain extending
agent, type and concentration of the emulsifying agent, the swelling or solubility of
the microcapsule wall, and the rate of reaction between the monomers. The
objective of this research was to investigate the morphology and microstructure
of polyurethane-urea microcapsules prepared by interfacial polycondensation of
methylene bis(phenyl isocyanate) as the multifunctional isocyanate, hexamethyl-
ene diamine as the diamine, anionic sodium lignin sulphonate as the emulsifying
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agent, and the herbicide 2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-

acetamide as the active agent.

Experimental

4,4 0-methylene bis(phenyl isocyanate) (MDI) with functionality of 2.2 and

equivalent weight of 113.6, and hexamethylene diamine (HMDA) with function-
ality of 2.0 and equivalent weight of 58, were obtained from Merck (Darmstadt,
Germany). The anionic emulsifying agent REAX-88B (Charleston Heights, SC,
USA), a sodium lignin sulphonate (SLS), is a registered trademark of Westvaco
Corp., and the herbicide alachlor, as the active encapsulating agent, with chemical
name 2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide, with 94.8%
For personal use only.

purity, is a registered trademark of Monsanto Corp (Saint Louis, MO, U.S.A.).

They were provided by the Agricultural Support Services Co. (Tehran, Iran), a
subsidiary of Iran’s Ministry of Agriculture. Sodium chloride and anhydrous
calcium chloride were obtained from Merck (Darmstadt, Germany). All chemicals
and reagents were used as received, without further puri®cation.
The following procedure was used for the preparation of microcapsules. To
prepare the oil phase, 12.6 g (5 £ 10¡2 mol) of MDI was added to a beaker
containing 200 g of herbicide alachlor, as the active agent, to provide a 6.3% w/w
solution of the isocyanate monomer in the oil phase. To prepare the aqueous
phase, 12 g of the SLS, as the emulsifying agent, was added to a beaker containing
300 g of distilled water to provide a 4% w/w aquoeus solution. To prepare the
aqueous HMDA solution, 5.8 g (5 £ 10¡2 mol) of HMDA was added to a beaker
containing 23.2 g of distilled water to provide a 20% w/w HMDA in water. The
aqueous and the oil phase were pre-heated to 558C in an oven before encapsula-
tion. For microencapsulation, the pre-heated aqueous phase was poured into a 1-1
stainless steel vessel, and it was allowed to mix for 30 s at an agitation rate of
5000 rpm. Next, the pre-heated oil phase was added slowly to the aqueous phase
over a 60 s time interval, while the agitation rate was kept at 5000 rpm. After the
addition of the oil phase, the mixing was continued for an additional 30 s. Then,
the 20% HMDA solution was added dropwise to the emulsion over a 60 s time
interval. After the addition of HMDA, the agitation rate was reduced to 2000 rpm
to reduce the shear rate and avoid breakup of the microcapsules. Formation of
the polymeric wall around the droplets was allowed to proceed for 60 min, while
the temperature of the reaction was kept constant at 608C by cooling or heating the
reaction vessel. After the completion of the microencapsulation reaction, the
agitation rate was reduced to 500 rpm, and 14 g of calcium chloride, equal to 4%
w/w of the aqueous phase, was added to the suspension to stabilize the micro-
 804 E. Jabbari

capsules. After the addition of calcium chloride, the suspension was mixed for
10 min at 500 rpm, bottled, and stored at ambient conditions. The per cent of the
active agent in the formulation was 35% w/w and the per cent of the polymeric
shell wall, for 100% conversion of the monomers, was 3.2%.
The microcapsules were examined visually with an optical microscope (Euro-
mex). A drop of the microcapsule suspension was placed on a microscope slide,
diluted with distilled water, and examined at a magni®cation of £100 or £400. The
average diameter and size distribution of the microcapsules were measured with a
Coulter particle size analyser (Coulter LS130) by injecting ¹1 ml of the micro-
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capsule suspension in the holding reservoir of the analyser.

For scanning electron microscopy examination, the microcapsule suspension
was spray dried to obtain dry powder using a Buchi 190 Mini spray dryer. The
inlet and outlet temperatures of the dryer were 120 and 708C, respectively. The
compressed air pressure was 2.1 bar, and the air ¯ow rate was 12 1/min. Before
spray drying, the microcapsule suspension was diluted with distilled water in a 3:1
ratio to reduce the viscosity. The volumetric ¯ow rate of the liquid in the dryer was
22 ml/min. The moisture content of the dried microcapsules after drying was 8%,
which was measured by weighing the microcapsules before and after complete
drying in an oven at 1208C for 10 min.
The size distribution and surface morphology of the spray-dried microcapsules
were examined with SEM. The sample was sprinkled on a double stick tape which
For personal use only.

was attached to a SEM mount. Then, the sample was sputter coated with a
combination of gold and palladium and examined with a JOEL 840 SEM at an
accelerating voltage of 10 KeV.
The microstructure and morphology of the spray-dried microcapsules were
examined with transmission electron microscopy (TEM). The spray-dried sample
was immersed in a sucrose-polyvinyl pyrrolidone solution for 30 min and then the
solution was frozen in liquid nitrogen. The frozen sample was sectioned with a
glass knife at ¡858C in an ultramicrotome (Leica Ultracut E) equipped with a
liquid nirogen-cooled cryochamber. Dry sections, with thicknesses in the range of
80±100 nm, were picked up with eyelash probes and placed on a carbon coated
copper grid. Then, the grid was removed from the cryochamber and allowed to
warm to room temperature. The sections were examined with a Hitachi H-600
TEM with an accelerating voltage of 75 KeV.
X-ray microprobe analysis was used to map the spatial distribution of sodium,
calcium, and sulphur elements in the polyurea shell of the microcapsules. Spray-
dried microcapsules were embedded in a cyanoacrylate fast curing resin to allow
rapid preservation of the microcapsule structure. Then, the embedded sample was
microtomed with a glass knife at ¡858C with an ultramicrotome (Leica Ultracut E)
to reduce the surface roughness to less than 0.1 mm. X-rays were collected from the
sample with a Cameca x-ray microprobe analyser equipped with a Kevex x-ray
spectrometer operating at an accelerating voltage of 10 KeV. The electron beam
was scanned over the area of interest on the sample by stepping the beam by digital
positioning. The beam was paused at each point for a known interval of time for x-
ray collection. The frequency of the collected x-rays were compared with known
standards for sodium, calcium, and sulphur.
 Morphology and structure of microcapsules 805
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Figure 1. Changes in pH and per cent conversion as a function of reaction time for
interfacial polycondensation of MDI with HMDA, based on the measured concentra-
tion of HMDA monomer.

Results and discussion

For personal use only.

The addition of the aqueous HMDA solution changed the pH of the micro-
encapsulation reaction mixture from 7.5 to 11.8. As the HMDA reacted with the
isocyanate, the pH of the reaction mixture dropped. The changes in the pH as the
HMDA was consumed could be used to follow the conversion or the extent of the
reaction. Figure 1 shows the changes in pH and conversion, based on the HMDA
monomer, as a function of the reaction time. As the microencapsulation reaction
proceeded, the pH changed from 11.8 to 7.7 and the conversion reached 98% after
60 min. The size distribution of the microcapsules was measured by a Coulter
particle size analyser. The mean of the distribution was 3.4 mm and the standard
deviation of the mean was within the range of 2.7±4.1 mm with 95% con®dence
limits. The mean-to-median ratio was 1.4, which indicated that the distribution
was slightly right skewed.
The internal structure of the microcapsules was investigated with TEM. The
TEM micrograph in ®gure 2 shows the cross-section of microcapsules at 14 000
magni®cation. According to this ®gure, the microcapsules have a micro-reservoir
structure in which the wall extends well into the core and the active agent is
accommodated by the micro-reservoirs, distributed uniformly throughout the
entire volume of a microcapsule. The shadows around the boundary of micro-
capsules are due to folding of the wall at the edges. According to this ®gure, the
thickness of the polymeric ®lm surrounding the microcapsule and the polymeric
®lms forming the internal structure are approximately the same, in the order of 25±
50 nm. Based on the observed morphology, the following mechanism can be
proposed for the interfacial polycondensation reaction. After the addition of
HMDA to the emulsion, MDI from the droplet phase and HMDA from the
aqueous phase react at the interface to form a thin polyurea ®lm encompassing
the droplets. The polyurea ®lm is formed on the oil side of the interface, due to the
higher solubility of HMDA in the oil phase compared to the solubility of MDI in
 806 E. Jabbari
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Figure 2. TEM micrograph of the cross-section of microcapsules at £14 000 magni®ca-

tion. The shadows around the boundary of microcapsules are due to folding of the
wall at the edges. Thickness of the polymeric ®lm surrounding the microcapsules and
the polymeric ®lms forming the internal structure of the microcapsules are in the
order of 25±50 nm, respectively.

the aqueous phase. The formation of a thin polymeric ®lm around the droplets
occurs within the ®rst few minutes after the addition of HMDA, since the reaction
rate between MDI and HMDA is relatively fast, as reported previously (Yadav et
al. 1996). Based on the TEM micrograph, the thickness of the wall does not
increase with reaction time. However, HMDA di€ uses through the wall and
dissolves partially in the oil phase. In the oil phase, HMDA reacts with MDI to
form partially crosslinked polyurea, which is insoluble in the oil phase and phase
separates to form the micro-reservoir morphology observed in the TEM micro-
graph. The results of this research clearly indicate that the permeability of the
water soluble monomer in the polyurea ®lm and its solubility in the oil phase have
a signi®cant e€ ect on the morphology and microstructure of microcapsules
prepared by interfacial polycondensation.
 Morphology and structure of microcapsules 807
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Figure 3. SEM micrograph of the microcapsules extracted with 9.5% w/w calcium
chloride aqueous solution after 24 h of drying under ambient conditions at £2000
magni®cation. Microcapsules extracted with calcium chloride aqueous solution
remained stable after drying.

The release behaviour of the microcapsules was studied in deionized water and
9.5% w/w calcium chloride aqueous solution at 258C. Approximately 1 g of the
For personal use only.

spray dried microcapsules were dissolved in 200 ml of deionized water or calcium

chloride aqueous solution, extracted for 30 min, ®ltered through a Whatmen No.4
®lter paper, and allowed to dry under ambient conditions. More than 50% of the
microcapsules extracted with deionized water collapsed after 24 h of drying, but
relatively all of the microcapsules extracted with calcium chloride aqueous solution
remained stable. Figure 3 shows the SEM micrograph of microcapsules extracted
with calcium chloride aqueous solution after 24 h of drying under ambient con-
ditions at £2000 magni®cation. When the same experiments were performed with
sodium chloride aqueous solution with the same molarity as the calcium chloride
solution, results similar to extraction with deionized water were obtained. There-
fore, the multivalent salt, calcium chloride, plays a major role in stabilizing the
microcapsule structure, most likely by interacting with the anionic surfactant,
SLS.
To further investigate this interaction, the phase behaviour of SLS aqueous
solution was studied as calcium chloride was added to the solution. It was observed
that the viscosity of a 40% w/w SLS aqueous solution increased by two orders of
magnitude as calcium chloride was added at ambient conditions. This indicated
that a physical gel is formed as calcium chloride is added to SLS aqueous solution.
In fact, upon the addition of calcium chloride to SLS aqueous solution, two phases
are formed in which one phase is concentrated and the other is dilute with respect
to SLS. Figure 4 shows the volume ratio of the gel phase to the dilute phase as
calcium chloride is added to SLS solution. The abscissa in ®gure 4 is the molar
ratio of calcium to carboxylic and phenolic groups of SLS. It is believed that the
interaction between calcium chloride and SLS is mainly by electrostatic inter-
actions between the positive calcium ion and the negatively charged carboxylic and
phenolic groups. According to this ®gure, as the molar ratio of calcium to
carboxylic acid and phenolic groups of SLS increased from 0 to 1.0, the volume
 808 E. Jabbari
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Figure 4. Volume ratio of the gel phase to the dilute phase for 45% w/w sodium lignin
sulphonate aqueous solution as a function of calcium chloride concentration. The
abscissa is the molar ratio of calcium to carboxylic and phenolic groups of the sodium
lignin sulphonate.

per cent of the gel to the dilute phase increased from 0 to nearly 60%. This clearly
For personal use only.

indicates that the multivalent positive calcium ion physically crosslinks the SLS
chains by interacting with the negatively charged carboxylic and phenolic groups,
with subsequent phase separation, to form a concentrated gel phase. According to
the same ®gure, as the molar ratio of calcium to carboxylic and phenolic groups
increased from 1.0 to 6.8, the volume per cent of the gel phase to the dilute phase
increased from 60±82%. When similar experiments were performed with sodium
chloride instead of calcium chloride, phase separation did not take place. More-
over, X-ray microprobe analysis showed excellent spatial correlation between the
elements of calcium and sulphur around the microcapsules, whereas poor spatial
correlation was observed for the elements of sodium and sulphur. Since only SLS
contains the element sulphur among the microcapsule components, calcium ions
interact with SLS to form a gel which increases the microcapsule stability.
These results indicate that as calcium chloride is added to the aqueous
suspension of microcapsules containing SLS, a gel phase is formed. This gel
phase encompasses the microcapsules to increase their stability and to modify their
release behaviour. When the microcapsule suspension was washed with calcium
chloride aqueous solution and allowed to dry, the gel layer encompassing the
microcapsules did not dissolve and, therefore, they remained stable after drying.
On the other hand, when the microcapsules suspension was washed with deionized
water and allowed to dry, the calcium ions in the gel layer di€ used to the aqueous
phase by the action of osmotic force, the gel dissolved, and the microcapsules
ruptured after drying.

Acknowledgements

The author wishes to acknowledge the research council of Iran’s Ministry of

Agriculture for ®nancially supporting this research.
 Morphology and structure of microcapsules 809

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