Microencapsulation
Methods and
technologies
Denis Poncelet
ENITIAA, Nantes, France
&
Capsuale, Nantes, France
Microencapsulation ?
• Entrapment of active materials inside
microparticles for:
• Immobilisation
• protection
• controlled release
• structuration
• functionalisation
ENITIAA, Nantes, France
ENITIAA, Nantes, France
&
Microencapsulation ?
• Entrapment of active materials inside
microparticles for:
• Immobilisation
• protection
• controlled release
• structuration
• functionalisation
&
Capsulae, Nantes, France
Capsulae, Nantes, France
ENITIAA, Nantes, France
Encapsulation of flavors
&
Capsulae, Nantes, France
Microencapsulation ?
Immobilisation
Volatile compounds
Microencapsulation ?
• Entrapment of active materials inside
microparticles for:
http://www.mane.com/
Continuous processing (bio-cells & enzymes)
Lactic bacteria culture
immobilized
> 10 10
free cells
< 10 8
cells/ml
cells/ml
ENITIAA, Nantes, France
Microencapsulation ?
&
Capsulae, Nantes, France
Protection
Taste masking
Storage
www.encap.com
Vitamin A / monosodium glutamate
appearance (white)
protection (water, T, ligth)
Processing
www.human-nutrition.basf.com
Medium protection
www.balchem.com
Ferrous fumarate agglomerated and
coated with 60% hydrogenated soy oil
using the Wurster process. 100-450 !m
Meatshure
Immune protection
Digestion
http://www.islet.com
www.customprobiotics.com
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
• Immobilisation
• protection
• controlled release
• structuration
• functionalisation
ENITIAA, Nantes, France
Langerhans islets
encapsulation
&
Capsulae, Nantes, France
Microencapsulation ?
• Entrapment of active materials inside
microparticles for:
• Immobilisation
• protection
• controlled release
• structuration
• functionalisation
ENITIAA, Nantes, France
nanocapsule release
&
Capsulae, Nantes, France
Microencapsulation ?
Controlled release
Diffusion-rehydration-degradation-rupture
Chemical - physical - mechanical factors
% of optimum
225
Ideal
real
Toxicity
150
75
0
0
1
2
3
4
5
6
(immobilisation + protection)
versus release
7
Time (d)
Kinetics = structure + size distribution
ENITIAA, Nantes, France
Microencapsulation ?
•
•
•
•
•
•
•
&
Capsulae, Nantes, France
Structuration
• Immobilisation
• protection
• controlled release
• structuration
• functionalisation
ENITIAA, Nantes, France
Liquid > solid
Dispersibility
Flowdability
Tabletisation
Dust free
&
Capsulae, Nantes, France
Microencapsulation ?
• Entrapment of active materials inside
Liquid or gaz to solid
microparticles for:
Dispersibility
Solubility
Flowdability
Tabletisatisable
Spic and Span
Hygroscopicity controle
Dust free powder (enzyme)
ENITIAA, Nantes, France
• Entrapment of active materials inside
microparticles for:
www.salvona.com
300
Microencapsulation ?
&
Capsulae, Nantes, France
• Immobilisation
• protection
• controlled release
• structuration
• functionalisation
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Spic and Span
Microencapsulation ?
Fonctionalisation
Visual aspect
Methods : 3 steps
Customer advising
Marketing
Incorporation
of the active ingredient within the
microcapsule core/matrix
Dispersion
of the core as dropplet
or
mixing of core particles
Stabilisation
(solidification)
of the dropplets
or
of coating layer around particles
End user applications
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
Methods ...
Capsulae, Nantes, France
Methods ...
Incorporation
liquid core
(water, solvent, melt)
Incorporation solution, emulsion,
suspension
&
solid core
(particles, powder)
absorbtion, layering,
agglomeration
liquid core
Dripping
Spraying
solid core
Emulsion
Spray
coating
liquid
liquid
Dispersion
Coating
solution
Dispersion
Air
Stabilisation
Stabilisation
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Suspension
coating
Methods ...
Methods ...
Incorporation
Dispersion
Stabilisation
Solidification
liquid core
Dripping
Spraying
Prilling
Spray
cooling
Evaporation
(drying)
Emulsion
Hydrogel
beads
Solvent Spray (drying)
evaporation
coating
Internal
gelation
Spray
chilling
Polymerisation
Interfacial
in situ pol..
Precipitation
coacervation
coacervation
Molecular
interaction
Interfacial
coacervation
ENITIAA, Nantes, France
Methods ...
liposomes
&
Suspension
coating
Spray
coating
Hotmelt
spray coating
Spray
drying
Gelation
solid core
• Laminar flow (gentle conditions)
• Providing small (200 µm > 1000 µm)
• Low size dispersion (s= 5 > 20 %)
• Good productivity (mL/h > L/h)
polymer
coating
Dry powder
coating
Ionic
coating
Capsulae, Nantes, France
ENITIAA, Nantes, France
Methods ...
Driping : droping
de
Dripping
&
Capsulae, Nantes, France
driping: co-axial air flow
$"
'
mg = & d 3# ) = "de*+
%6
(
mg+ 3"µud + 0,055"#u2 d 2 = "de$%
3
model
!
2
u
u
d (mm)
!
d (mm)
3
2
0
0,2
0,4
0,6
de (mm)
Low flow - large capsules
ENITIAA, Nantes, France
&
Size dispersion
1
1
0
Flow limited by
the jet formation
(50 mL/h)
data
Capsulae, Nantes, France
0,8
1,0
Jet formation faster
if u increases
0
5 10 15 20 25 30 35 40
u (m/s)
Low flow - small capsules but size dispersion
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Dripping : Electrostatic generator
Methods ...
Dripping: vibrated nozzle
Jet formation
% U2 (
mg = "de # o '1$ 2 *
& U cr )
4 #
$ dj
uj "
!
http://www.nisco.ch
U
d (mm)
3
jet
formation
2
u!
j
1
0
dj
0
1
2
3
4
5
6
7
8
!
U (kV)
!
Very low flow - small capsules
ENITIAA, Nantes, France
Methods ...
&
f=
" dj
http://www.inotech.ch
"opt = 4,05
d = 1,89 d j
http://www.nisco.ch
Low viscous liquid (200 mPa.s)
Capsulae, Nantes, France
ENITIAA, Nantes, France
!
Dripping: vibrated nozzle
uj
&
Capsulae, Nantes, France
Methods ...
Dripping: vibrated nozzle
20
Fmin (l/h)
Fmax (l/h)
15
10
http://www.inotech.ch
5
0
0
500
1000
1500
2000
d (µm)
" / d = 5 #10%
http://www.brace.de
!
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Dripping: jet cutter
Methods ...
Dripping : rotating devices
www.swri.org
http://www.genialab.de
F (kg/h)
80
" / d = 5 #10%
60
" = 5000 Hz
20
0
Particle and coating technology
www.pctincusa.com
200 400 600 800 1000 1500 2000
d (µm)
!
ENITIAA, Nantes, France
&
http://www.spraysas.com/
Capsulae, Nantes, France
Methods ...
Prilling : dripping & cooling
Melt
Melt material
• fatty acid, triglycerides, ester
• parafin
ENITIAA, Nantes, France
Cristalisation !
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Hydrogel beads: dripping + gelation
Alginate
•
•
Active ingredient incorporated as
• solution
• emulsion
• suspension
Cold air
www.niro.com
40
!
High viscosity
(>200 mPa.s)
high productivity
“low” dispersion
high spray surface !
Ionic gelation
•
•
Alginate in CaCl2
Chitosan in Phosphate
Thermal gelation
•
•
K-carraghenane
agar, agarose
2 - 5 % polymer - porous beads
CaCl2
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Methods ...
Microcapsules by dripping
polymer or ions
Spray technologies
• co-extrusion
• inverse gelation
• CaCl in alginate
2
(Cacl2 in water or oil)
• interfacial coacervation
• Alginate (-) in Chitosan (+)
• Cellulose sulfate in PPDMAC
polymer
High control of the permeability
ENITIAA, Nantes, France
Methods ...
&
Large productivity (tons per hours)
dropplets 30 -100 µm - large size distribution
Capsulae, Nantes, France
ENITIAA, Nantes, France
Methods ...
Spray technologies
• Spray drying
• water solution
• energy, overheating, low yield
• Spray cooling
• melt solution
• low energy, high yield
• Spray chilling
• thermogel solution
• porous beads
ENITIAA, Nantes, France
&
&
Capsulae, Nantes, France
Spray technologies
Temperature
moisture
Capsulae, Nantes, France
temperature
Water
water removal
low drying
surface
capacity
water content
aroma
Time (s)
temperature
Water
high drying
water removal
water content
surface
capacity
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Emulsion technologies
Methods ...
Emulsion technologies
Turbine reactor with baffles
• turbulent flow (kolmogorov theory)
d
= k We"2/ 3
D
Shear driven
dispersion
Emulsion
microencapsulation
Physicochemical
dispersion
micro-emulsion
nanoencapsulation
• d = 100 - 800 µm
size
• surfactant to decrease
!
u !
•
D
Methods ...
&
Capsulae, Nantes, France
Emulsion technologies
Static Mixer
• d = 10 - 500 µm
• surfactant to decrease size
! • " / d = 20 # 40%
Cacrit
rotational
"c # Cacr
2 $
Static
mixer
• productivy = L /min.cm2
• time of dispersion < 1 sec
elongation
!d / !c
!
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
" / d = 30 # 50%
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Emulsion & chemical reaction
Continuous
oil phase
• laminar flow
d=
D"u 2
#
• productivy = 25 % reactor volume
• time of mixing 5 - 20 min
!
ENITIAA, Nantes, France
We =
ClOC-(CH3)6-COCl
HCl
Polyamide
membrane
Aqueous
dropplet
Continuous
water phase
NH2-(CH3)6-NH2
• interfacial or internal
• polymerisation or
reticulation
• direct membrane formation
or coacervation
NH2-(CH3)6-NH2
HCl
Polyamide
membrane
oil
dropplet
ClOC-(CH3)6-COCl
Nylon
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Chitosan
Methods ...
Methods ...
Emulsion & solvent removal
Polymer + solvent
Solvent
Solvent
Solvent
Emulsion : coacervation
Coacervation
Acid or salt
Solvent
• Simple : 1 polymer
• Complex : 2 polymers
• Acacia gum /gelatin
• + acid
• + glutaraldehyde
Oil
P ! Ps
P > Ps
Water
Polymer(s)
solution
P < Ps
• extraction &/or evaporation
• polylactic acid, polyglycolic acid in dichloromethane
• expensive, organic solvent, applications in pharmacy
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
Emulsion : internal gelation
[free Ca] (mM)
50,0
37,5
25,0
12,5
0
carbonate
tartrate
2
3
4
Liposomes and molecular inclusion
citrate
oxalate
5 5,5 6
7
8
Liposomes
pH
gelification time (sec)
Vegetal Oil
CaCO3 + 2H + " Ca 2+ + H 2CO3
!
molecular inclusion
carbonate
citrate
500
375
Capsulae, Nantes, France
Methods ...
Methods ...
Internal gelation
Acetic
Alginate +
acid
CaCO3
&
250
125
0
6.4
6,8
7,3
7,7
8
pH
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Coating technologies
evaporatio n
(drying )
co ating
spray
•
im pact, sp reading,
adhesion, co alescence
•
e vaporation
(drying)
co ating
sp ray
agglomeratio n
•
ENITIAA, Nantes, France
Methods ...
Coating technologies: fluid bed
Mixing
fluid bed
pan coater
spray
coating
agglomeration
layering
u = UT " n
•
•
•
•
•
!
Spray =
•
•
solution, emulsion, suspension, powder
&
Capsulae, Nantes, France
polymer, filler, surfactant, active
Coating technologies: fluid bed
Tangential
“Spouted”
Wurster
www.encap.com
ENITIAA, Nantes, France
Methods ...
Top spray
packed expanded fluidized transported
particle bed status
&
Capsulae, Nantes, France
Methods ...
Coating : continuous process
2,00
2,00
1,50
1,50
1,00
1,00
0,50
0,50
0,00
0,00
1,00
2,00
3,00
0,00
0,00
1,00
time
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
2,00
time
3,00
Methods ...
Coating technologies: pan coater
Methods ...
Coating: spray + evaporation
Evaporation (spray coating)
evaporatio n
(drying )
co ating
spray
•
im pact, sp reading,
adhesion, co alescence
spray = solution, emulsion, suspension
• high concentrate solution
•
Evaporation
• slow process (1-2 h)
• energy demand
• high temperature of input air
• risk of product overheating
http://www.glatt.de
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Methods ...
Coating : spray + cooling = hotmelt
h ot m elt
coatin g
sp ray
Solidification (hot melt coating)
ENITIAA, Nantes, France
&
Methods ...
Coating : dry powder technology
bind er
spray
Coalescence (dry powder
coating)
evaporatio n
(drying )
• spray = fine powder + plastifiant
• Starch + triethyl citrate
• fast process (15 min)
• limited material choice
• air at room temperature
• porous coating
• Curing step
• spray = hot melt
im pact, sp reading,
adhesion, co alescence
• fast process (20 - 30 min)
p owder
spray
• limited coating material choice
Coo ling air
• cold air air
• no risk of overheating
• low energy demand
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Capsulae, Nantes, France
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
HCl (pH 4)
ENITIAA, Nantes, France
&
Buffer
Capsulae, Nantes, France
Tendencies ...
•
•
•
•
•
•
Lactic cell immobilization
Langerhans islet isolation
Expansion
Cosmetic enzyme encapsulation
Diversification Yogourth production & chesse ripening
Beer production and maturation
Probiotic
& nutraceutic encapsulation
Sophistification
Nitrogen fixing cell soil innoculation
Artificial insemination
Sizes
Brown sugar flowing powder
Flavor & plant extract encapsulation
Environment
Biochemical production or conversion
Single component glue system
Scale-up
Low shear oxygen transfer
Carcinogen detection during digestion
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Non-patent (7500)
1600
Patent (11000)
1400
1200
1000
800
600
400
2003
2001
1997
1999
1995
1991
1993
1989
1985
1987
1983
1981
0
1977
200
1979
Alginate beads +
proteine + ester
1800
1975
Covalent hydrogel bead coating
2000
1971
Alginate solution 0.2 %
• Expansion
• Diversification
• Sophistification
• Sizes
• Environment
• Scale-up
1973
PLL or chitosan 0.2 %
filtration
washing
1967
filtration
washing
1969
Ionic hydrogel bead coating
Alginate beads
Tendencies ...
1965
Coating in suspension
Number of documents
Methods ...
Year
From Bojana boh (2003) MLL vol. 6, Citus Book, london, UK.
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Tendencies ...
2 enzymes
• Expansion
• Diversification
• Sophistification
• Sizes
• Environment
• Scale-up
Water
glucose
HSCN
OSCNhypothiocyanite
Listeria
bactericide
lactoperoxidase system (LPS)
• material immobilization !enzymes +
susbstrates"
• enzyme protection !storage"
• controlled release of end#products
• control of hygroscopy
• flowdability & dispersibility
• high reaction e$ciency
• long term & more e$cient action
• easy to use for underdeveloped
countries
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
Tendencies ...
• Expansion
• Diversification
• Sophistification
• Sizes
• Environment
• Scale-up
ENITIAA, Nantes, France
Tendencies ...
• Expansion
• Diversification
• Sophistification
• Sizes
• Environment
• Scale-up
very small
very large
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
Methods ...
Tendencies ...
Emulsion
• Expansion
• Diversification
• Sophistification
• Sizes
• Environment
• Scale-up
Vegetable or
mineral oil
membrane forming
material + cells
Cross-linker
static mixers
Nylon
Chitosan
&
Capsulae, Nantes, France
Conclusions ...
• Encapsulation covers a broad domaine of activities
• It is a very active industrial topic
• Progress has to be done and are in process to be
Coating
http://www.microencapsulation.de
http://Bioencapsulation.net
http://COST865.Bioencapsulation.net
ENITIAA, Nantes, France
&
Capsulae, Nantes, France
ENITIAA, Nantes, France
&
Capsulae, Nantes, France