Encapsulation technologies:

Transcription

1 Encapsulation technologies: A general overview Capsulae

2 Presentation outline 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

3 Introduction 1. Introduction Definitions Objectives Markets 3. Analyses 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. 3

4 Introduction Matrix structure, active(s) in orange 1. Introduction Definitions Objectives Markets 3. Analyses 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 particle with clearly visible active Core / shell structure, active(s) in orange Shell of capsule containing a liquid core 4

5 Introduction 1. Introduction Definitions Objectives Markets 3. Analyses 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 5

6 Introduction 1. Introduction Definitions Objectives Markets 3. Analyses 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. O 2, light, T C H 2 O, ph) Protect handlers and consumers (e.g. detergent proteases, pesticides) Encapsulation of essential oil in biopolymer beads Lyophilisate without (up) and with coating (down) 6

7 Introduction 1. Introduction Encapsulation: objectives (2/2) Definitions Objectives Markets 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) 3. Analyses Salt release in aqueous Structuration / Functionalization: solution (microsphere) 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 Samples produced using different encapsulation technologies 7

8 1. Introduction Definitions Objectives Markets Introduction Encapsulation: markets Microencapsulation can be applied to all sectors of industrial activity: Agriculture & Environment Insecticides and fungicides Herbicides and fertilizers Repellents and larvicides Plant biocontrol & bionutrition Water, soil, air treatment Chemistry Adhesives and sealants Paints and coatings Building & construction materials Self-healing materials & PCM 3. Analyses Food & Feed Flavouring agents & sweeteners Enzymes & micro-organisms Vitamins, minerals & amino acids Plant extracts, aromas, fragrances Unsaturated fatty acids Home & Personal Care Cosmetic creams S h am p o o, to oth p a s te, soap & shower gels Washing powders & washing-up liquids Household products Human & Animal Health Vaccination & drug delivery Artificial insemination Bioartificial organs Cell therapy 8

9 Encapsulation processes General principle Dripping Spray-drying Prilling Coating Emulsion 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 9

10 Encapsulation processes G en er al p r in c ip le Dripping Spray-drying Prilling Coating Emulsion 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 Dripping (multiple nozzles) Vibrating jet breakage (up) and spinning disk device (down) 10

11 Encapsulation processes G en er al p r in c ip le Dripping Spray-drying Prilling Coating Emulsion 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 Spray-dried powder (encapsulated PUFA) SEM observation of microparticles produced by spray-drying 10 µm 11

12 Encapsulation processes G en er al p r in c ip le Dripping Spray-drying Prilling Coating Emulsion 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 Encapsulated minerals Encapsulated vitamins 12

13 Encapsulation processes G en er al p r in c ip le Dripping Spray-drying Prilling Coating Emulsion 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 mm SEM observation of sections of coated minerals Fluid-bed coating (bottom-spray) 13

14 Encapsulation processes G en er al p r in c ip le Dripping Spray-drying Prilling Coating Emulsion 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 Particles prepared by double emulsion (w/o/w) 20 µm Particles prepared by o/w emulsion and interfacial polymerization 14

15 Size measurements Microscopy Thermo-mechanical properties Powder properties Microbiology Quantification 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 Minerals inside microparticles of fatty acids (optical microscopy) 10 µm Surface of microparticles produced by emulsion / solidification (SEM) Fluorescent confocal microscop (along Z-axis) of microcapsules produced by double emulsion 15

16 Analysis Size measurements Microscopy Thermo-mechanical properties Powder properties Microbiology Quantification 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 Breakage of core / shell capsule containing oil Uncoated (left) & coated (right) freeze-dried probiotic bacteria after storage at high Aw value 16

17 Analysis Microbiology (bacteria, yeast, fungi): Size measurements Microscopy Thermo-mechanical properties Powder properties Microbiology Quantification 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 NaCl concentration (mmol/l) Immobilized cell culture (left) & cell enumeration (right) Water NaCl Stearic/palmitic acid blend Candelilla wax carnauba wax Time (secondes) Effect of material coating on the release of NaCl in solution J. Agric. Food Chem. 2012, 60 (43),

18 Conclusion Selection Industrialization Capsulae 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 (O 2, H 2 O, 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 18

19 Conclusion Encapsulation technologies: industrial scale Selection Industrialization Capsulae 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 Production costs 1,2 1 0,8 0,6 0,4 0,2 0 Dripping Emulsion / Stabilization Coating Prilling Spraydrying Productivity 19

20 Conclusion Selection Industrialization Capsulae 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 20

21 Visit us at capsulae.com