Post on 06-Feb-2018
Encapsulation technologies: A general overview
© Capsulae
Introduction • Definition of encapsulation• Objectives and markets
Encapsulation technologies • Dripping• Spray-drying• Prilling• Coating• Emulsion / Stabilization
Characterizations • Particle size measurements• Microscopy• Thermo-mechanical properties• Powder properties• Microbiology• Quantification, release kinetic profiles
Conclusion • Selection of a technology• Industrialization • Capsulæ, company and services
Presentation outline
3 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Introduction
Encapsulation: definition and concepts
Encapsulation relates to technologies which enable to formulate one active compound (or more), inside individualized particles with a specific geometry and properties.
Terminology: encapsulation, microencapsulation, or nanoencapsulation? • Encapsulation defines no size notion• Microencapsulation usually refers to sizes ranging
from 1 µm to 1 mm• Nanoencapsulation is used for nanometric sizes but
sometimes refers to sizes ranging up to 1 µm or few micrometers
The current presentation focuses on sizes ranging from 1 µm to few millimeters.
1. Introduction
DefinitionsObjectives
Markets
2. Technologies3. Analyses
4. Conclusion
4 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Introduction
Encapsulation: definition and concepts Structures of particles:
• Matrix structure: dispersion of active compound(s) in the encapsulation material (beads, microparticles, microspheres)
• Core / shell structure: the active compound (pure or not) is confined as one core by one shell or more (multi-shell) (microparticles, microcapsules)
• Both structure can be combined to design new ones: (matrix core) / shell, or core / (matrix shell) (two compounds, one in the core and another one in the shell)…
Matrix structure, active(s) in orange
Matrix structure particle with clearly
visible active
Core / shell structure, active(s) in orange
Shell of capsule containing
a liquid core
1. Introduction
DefinitionsObjectives
Markets
2. Technologies3. Analyses
4. Conclusion
5 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Introduction
Encapsulation: definition and concepts Active compounds:
• Physical state: solid, liquid, gas• Hydrophilic or hydrophobic• Granulometry (powder, particle): up to few mm• Active compound content up to 900 mg per g of final particle
Encapsulation materials (non exhaustive list):
• Biopolymers (vegetable, animal or bacterial sources): alginates, pectins, chitosans, carrageenans, Arabic gums, cellulose derivatives, starches, gelatins, milk proteins, gellan gum, …
• Waxes and fats (vegetable, animal sources): carnauba wax, candelilla wax, stearins, shellac…
• Surfactants: lecithins, Spans®, Tweens®…• Synthetic polymers: PVA, PEG, polycaprolactone, PLGA, isocyanates,
polyamide, polyurea, polyurethane, melamine formaldehyde…
The appropriate grade shall be selected:
• Food• Feed• Cosmetic• Pharma• Others
1. Introduction
DefinitionsObjectives
Markets
2. Technologies3. Analyses
4. Conclusion
6 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Introduction
Encapsulation: objectives (1/2) Encapsulating an active principle meets four main objectives which can be combined.
Immobilization:
• Volatile compounds (e.g. fragrances, flavors)• Continuous bioprocessing
(e.g. enzymes, micro organisms)
Protection / Stabilization:
• Stabilize and protect the active ingredient against external environemental factors (e.g. O2, light, T°C H2O, pH)
• Protect handlers and consumers (e.g. detergent proteases, pesticides)
1. Introduction
DefinitionsObjectives
Markets
2. Technologies3. Analyses
4. Conclusion
Encapsulation of essential oil in biopolymer beads
Lyophilisate without (up) and with coating (down)
7 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Introduction
Encapsulation: objectives (2/2) Controlled release (at a given time, upon the action of a selected trigger) :
• Diffusion, rehydration, degradation, rupture• Triggered release by a specific condition
(chemical, physical, mechanical factor): temperature, pH value, water, pressure…
• Sustained release with specific kinetics profiles (e.g. vitamins, drugs, flavors, pesticides)
Structuration / Functionalization:
• Conversion of liquid or gas to solid• Taste, odor or color masking• Surface properties and rheology of powders;
dust free powder• Visual aspect and marketing concept
1. Introduction
DefinitionsObjectives
Markets
2. Technologies3. Analyses
4. Conclusion Salt release in aqueous solution (microsphere)
Samples produced using different encapsulation
technologies
8 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
1. Introduction
DefinitionsObjectives
Markets
2. Technologies3. Analyses
4. Conclusion
Introduction
Encapsulation: markets Microencapsulation can be applied to all sectors of industrial activity: Food & Feed • Flavouring agents & sweeteners• Enzymes & micro-organisms• Vitamins, minerals & amino acids• Plant extracts,
aromas, fragrances• Unsaturated fatty acids
Agriculture & Environment • Insecticides and fungicides• Herbicides and fertilizers• Repellents and larvicides • Plant biocontrol & bionutrition• Water, soil, air treatment
Home & Personal Care • Cosmetic creams • Shampoo, toothpaste,
soap & shower gels• Washing powders
& washing-up liquids• Household products
Chemistry • Adhesives and sealants• Paints and coatings• Building & construction
materials• Self-healing materials
& PCM
Human & Animal Health • Vaccination & drug delivery• Artificial insemination• Bioartificial organs• Cell therapy
9 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Encapsulation processes
General principe
1. Incorporation of the active ingredient within the microparticles
• Liquid core (active ingredient dissolved or dispersed in water, organic solvent, oil or melt; solution, emulsion, suspension)• Solid core (active ingredient available as powder, crystals, or liquid adsorbed on inert particles)
2. Dispersion (liquid core) or Agitation & spraying (solid core)
• Liquid core (formation of droplets via liquid/liquid or liquid/air dispersion): droplet extrusion (dripping), spraying, or emulsification• Solid core (spraying of coating material on particles under agitation; coating, layering, agglomeration): fluid bed coating, pan/drum coating
3. Stabilization of droplets (liquid core) or film formation (solid core)
• Solidification / Crystallization• Solvent evaporation or drying• Gelation (thermal, ionotropic)• Polymerization (in-situ or interfacial), Polycondensation • Precipitation / Coacervation (simple or complex) / Reticulation
1. Objectives
2. Technologies
General principleDripping
Spray-dryingPrillingCoating
Emulsion
3. Analysis4. Conclusion
10 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Encapsulation processes
Dripping / gelation technologies:
Methods: droplet extrusion (single or multi nozzle device, simple gravity, spinning disk, jet breakage systems, co-extrusion) of a (bio)polymer solution in a gelation bath or in ambient/cold air
Particles properties (standard):
• Size range: from 50 µm to 7-8 mm• Final state: wet (can be dried or lyophilized) • Active type: liquid, solid; hydrophilic or lipophilic• Active content: up to 400 mg/g (wet), 900 mg/g (dry)• Structure: matrix, core / shell (s), (matrix core) / shell
Main advantage(s):
• Biocompatibility• Low particle size distribution
Possible limitation(s):
• Diffusion through the biopolymer network / membrane
1. Objectives
2. Technologies
General principleDripping
Spray-dryingPrillingCoating
Emulsion
3. Analysis4. Conclusion
Dripping(multiple nozzles)
Vibrating jet breakage (up) and spinning disk device (down)
11 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Encapsulation processes
Spray-drying Method: spraying of an aqueous solution in hot air
Particles properties (standard):
• Size range: from 10 µm to 200 µm• Final state: dry • Active type: liquid, solid; hydrophilic or lipophilic• Active content: up to 400 mg/g• Structure: matrix
Main advantage(s):
• Very high productivity
Possible limitation(s):
• Thermal degradation
1. Objectives
2. Technologies
General principleDripping
Spray-dryingPrillingCoating
Emulsion
3. Analysis4. Conclusion
10 µm
Spray-dried powder (encapsulated PUFA)
SEM observation of microparticles produced
by spray-drying
12 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Encapsulation processes
Prilling (spray-cooling or spray-congealing): Method: formation of droplets by spraying of hot-melt material containing the active and solidification in ambient / cool air
Particles properties (standard): • Size range: from 50 µm to 500 µm• Final state: dry • Active type: solids or lipophilic liquid • Active content: up to 400 mg/g• Structure: matrix
Main advantage(s): • Very high productivity• Size control
Possible limitation(s):
• Thermal degradation
1. Objectives
2. Technologies
General principleDripping
Spray-dryingPrillingCoating
Emulsion
3. Analysis4. Conclusion
Encapsulated minerals
Encapsulated vitamins
13 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Encapsulation processes
Coating technologies: Method: spraying (top-spray, bottom-spray and tangential-spray) of an aqueous solution or a hot-melt material on particles under agitation (fluid-bed coating or drum/pan coating)
Particles properties (standard):
• Size range: from 100 µm to 5 mm• Final state: dry • Active type: solid or liquid adsorbed on a support • Active content: up to 900 mg/g• Structure: core / shell(s)
Main advantage(s):
• Control of final particle size and coating thickness• High active content
Possible limitation(s):
• Support properties
1. Objectives
2. Technologies
General principleDripping
Spray-dryingPrillingCoating
Emulsion
3. Analysis4. Conclusion
1 mm
SEM observation of sections of coated minerals
Fluid-bed coating (bottom-spray)
14 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Encapsulation processes
Emulsion / Stabilization technologies: Methods: stabilization of droplets formed by emulsion (o/w, w/o, double emulsion) by coacervation, reticulation, thermal gelation, solidification, interfacial or in-situ polymerization, solvent evaporation
Particles properties (standard):
• Size range: from 1 µm to 500 µm (nanometric size can be achieved)• Final state: wet (slurry); can be spray-dried or lyophilized• Active type: soluble in hydrophilic or hydrophobic liquids• Actif content: up to 900 mg/g• Structure: core / shell(s)
Main advantage(s):
• High active content• Small size
Possible limitation(s):
• High-shear process
1. Objectives
2. Technologies
General principleDripping
Spray-dryingPrillingCoating
Emulsion
3. Analysis4. Conclusion
20 µm
Particles prepared by double emulsion (w/o/w)
Particles prepared by o/w emulsion and interfacial
polymerization
15 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Analysis
Size measurements: particle size distribution • Laser diffraction (dry state or solution):
from 1 µm to few millimeters• Dynamic light scattering / zeta potential:
from 1 nm to 10 µm
Microscopy: structure and surface observation
• Scanning Electron Microscopy (SEM): surface observations• Binocular, optical microscope (bright or dark field),
fluorescence, confocal
1. Objectives
2. Technologies
3. Analysis
Size measurementsMicroscopy
Thermo-mechanical properties
Powder propertiesMicrobiology
Quantification
4. Conclusion
10 µm
Minerals inside microparticles of fatty acids
(optical microscopy)
Surface of microparticles produced by emulsion /
solidification (SEM)
Fluorescent confocal microscop (along Z-axis) of microcapsules produced by double emulsion
16 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Analysis
Thermal and mechanical characterizations: Dynamical mechanic analysis (DMA): • elastic properties, breakage force, release triggered by pressure (e.g. crushing)
Differential Scanning Calorimetry (DSC): • profiles, heat-triggered mechanisms (e.g. release during baking)
Powder properties:
Water content, water activity (aw) and water sorption isotherm: • control of biological and chemical reactions• limitation of water uptake and enhancement of shelf-life
Volumetric mass density (He pycnometry): • control of sedimentation or creaming of microparticles or microcapsules
Flowability (Carr index, Hausner’s ratio): • flowability improvement, decrease of friction phenomena, or fine powder formation
1. Objectives
2. Technologies
3. Analysis
Size measurementsMicroscopy
Thermo-mechanicalproperties
Powder propertiesMicrobiology
Quantification
4. Conclusion
Uncoated (left) & coated (right) freeze-dried probiotic bacteria after
storage at high Aw value
Breakage of core / shell capsule containing oil
17 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Analysis
Microbiology (bacteria, yeast, fungi):
• Culture of micro organisms (immobilized vs free cells)• Cell concentration, viability and survival rates:
over the encapsulation process, in specific conditions (e.g. simulated gastric conditions)
• Stability studies (controlled temperature and humidity)
Quantification: active titration, analysis, release profiles
• Conductivity, pH• Chromatography / Spectrometry• Spectroscopy, NMR…
1. Objectives
2. Technologies
3. Analysis
Size measurementsMicroscopy
Thermo-mechanicalproperties
Powder propertiesMicrobiology
Quantification
4. Conclusion
0
2
4
6
8
10
12
14
16
18
0 120 240 360 480 600 720 840 960 1080 1200
NaC
l con
cent
ratio
n (m
mol
/L)
Time (secondes)
WaterNaClStearic/palmitic acid blendCandelilla waxcarnauba wax
Immobilized cell culture (left) & cell enumeration (right)
Effect of material coating on the release of NaCl in solution
J. Agric. Food Chem. 2012, 60 (43), 10808-10814
18 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Conclusion
Factors to consider for selecting the appropriate technology
Active compound(s) / Core material
• Physico-chemical properties, physical state, size• Optimum concentration in the microparticles
Wall material / shell formulation
• Application(s): immobilization, protection, functionalization, release…• Stabilizing or barrier properties (O2, H2O, pH, T°C, shear,…)• Regulatory aspects: material grade, daily uptake (food/feed)…• Compatibility with core material• Release mechanism
Encapsulation process:
• Stability of core material during process• Encapsulation efficiency• Microcapsule morphology, particle size and distribution
Cost constraints, economic feasibility of large-scale production
1. Objectives
2. Technologies
3. Analysis
4. Conclusion
SelectionIndustrialization
Capsulae
19 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Conclusion
Encapsulation technologies: industrial scale
All the encapsulation technologies presented are fully available at lab, pilot and industrial scales.
Unit capacity could be up to 100’s of tons/year.
Costs study: equipment investment, materials cost, operating costs. Industrial production: internalization vs subcontracting
1. Objectives
2. Technologies
3. Analysis
4. Conclusion
SelectionIndustrialization
Capsulae
0
0,2
0,4
0,6
0,8
1
1,2
0 1000 2000 3000 4000 5000
Pro
duct
ion
cost
s
Productivity
Emulsion / Stabilization
Dripping
Coating
Spray-dryingPrilling
20 Capsulæ / Encapsulation technologies - © Capsulae
www.capsulae.com
Conclusion
Capsulæ: company presentation & services Capsulæ is a French Private Research and Technology Organization providing key R&D input to corporate innovation projects.
Capsulæ develops for its clients throughout the industrial world customized solutions which facilitate and optimize the performance of ingredients and active compounds, via microencapsulation.
Capsulæ offers a full range of services, including the following:
• Design of innovative solutions and feasibility studies• Encapsulation problem solving • Scaling-up studies and pilot-scale evaluation• Small pilot-scale production• Know-how licensing and technology transfer• Support at the industrialization stage
“From 10’s of grams to 10’s of kilos”
1. Objectives
2. Technologies
3. Analysis
4. Conclusion
SelectionIndustrialization
Capsulae
Visit us at capsulae.com