Microencapsulation Technologies

Microencapsulation technology has been used commercially since the 1950s when it became established as the basis for carbonless copy paper and is now used widely within the food processing, paper, pharmaceutical, agrochemical and cosmetic/persona; care industries. Similarly the technology has played a significant role in new developments in the textile industry and has been used for example to impart a range of long-lasting finishes to textile materials including, fragrances, antimicrobials, insecticides, fire retardants and temperature control phase change materials. Micro-encapsulation has also been the major force behind the rise of ‘Cosmeto-textiles’ delivering moisturising agents, vitamins and anti-wrinkle/anti-ageing active ingredients onto the skin. 

  

Microencapsulation is a process by which very tiny droplets or particles of liquid or solid material are surrounded or coated with a continuous film of a polymeric material. The ingredient to be encapsulated is usually referred to as the core material, however, can also be called the internal phase, active, encapsulate, payload or fill. The coating of the microcapsule is generally referred to as the wall material with shell, external phase and in some cases membrane also commonly used. The shape of the capsule is generally governed by the physical nature of the core material for example if the core material is a solid or crystalline material then the resulting capsule may be irregularly shaped. However, if the core material is a liquid, a simple spherical capsule containing a single droplet of active ingredient may be formed. 

Microcapsules range in size from 100s of microns, down to single microns although 10-40microns is probably most common. Nanocapsules are also available with sizes around or below 1 micron. Typically the core content will be around 80% by weight although anything up to 95% is possible.  Follow the links below to find out more about the major microencapsulation technologies and also other technologies used to store and control release active ingredients:

Chemical Based Microencapsulation Technologies

Coacervation      Interfacial Polymerisation      In-situ Polymerisation      Liposomes      Inclusion Complexation

 Coacervation

Sometimes called phase separation this technology is considered as the oldest true encapsulation technology first developed by the National Cash Register Company for carbonless copy-paper. Microencapsulation by coacervation, involves the phase separation of one or more hydrocolloids from the initial solution and the subsequent deposition of the newly formed coacervate phase around the active ingredient suspended or emulsified in the same reaction media. After being hardened, the wall of the microcapsules forms a cross-linked structure, thus the microcapsules have good thermal and moisture-resistant properties and can be used for controlled release applications. Coacervation generally involves a number of steps which are carried out under continuous agitation

1. Disperse the oil phase in a solution of a surface active hydrocolloid.2. Precipitate the hydrocolloid onto the oil phase by lowering the solubility of the hydrocolloid (add a non-solvent or change pH or temperature)3. Induce the formation of the polymer-polymer complex by addition of a second complexing hydrocolloid.4. Cross-link to stabilise the microcapsule5. Dry the material to form microcapsules with sizes in the range 10-250microns

Although many materials (e.g. alginates, chitosan, starch, and methyl cellulose) can be used the most commonly used are mixtures of proteins and anionic polysaccharides. Perhaps the most well-known example is gelatin and gum arabic.

At pH values above 6 both these materials are miscible, however when the pH is lowered below gelatin’s isoelectric point the net charge on the gelatin becomes negative and it then interacts with the positively charged gum arabic. The active ingredient, e.g. dye dissolved in an oil phase is first emulsified at about 40% in 10%w/v gelatin. The mixture is then added to about 2 parts gum arabic solution, maintaining the pH of the system above 5. As the pH is lowered to 4.5, microcapsules form from coacervate material positively charged gelatin and negatively charged gum arabic depositing around the oil droplets. After wall formation the wall is hardened by cross linking with for example glutaraldehyde or alternatively using transglutaminase.

 

 Interfacial Polymerisation

This technique is based on the classical technology involved in interfacial polycondensation polymerisation which is widely used to produce synthetic fibres such as polyester, nylon and polyurethane and is characterized by wall formation via the rapid polymerization of monomers at the surface of the droplets or particles of dispersed core material. A multifunctional monomer is dissolved in the core material, and this solution is dispersed in an aqueous phase. A reactant to the monomer is added to the aqueous phase, and polymerization quickly ensues at the surfaces of the core droplets, forming the capsule walls. Interfacial polymerization can be used to prepare bigger microcapsules, but most commercial interfacial polymerization processes produce smaller capsules in the 20-30 micron diameter range, or even smaller 3-6 micron diameter range for carbonless paper ink.

 

In interfacial polymerization, the two reactants in a polycondensation meet at an interface and react rapidly. The basis of this method is the classical Schotten-Baumann reaction between an acid chloride and a compound containing an active hydrogen atom, such as an amine or alcohol, polyesters, polyurea, polyurethane. Under the right conditions, thin flexible walls form rapidly at the interface.

 

 In-situ polymerisation In situ polymerization is a chemical encapsulation technique very similar to interfacial polymerization. The distinguishing characteristic of in situ polymerization is that no reactants are included in the core material. All polymerization occurs in the continuous phase, rather than on both sides of the interface between the continuous phase and the core material, as in interfacial polymerization. Examples of this method include urea-formaldehyde (UF) and melamine formaldehyde (MF) encapsulation systems. Typically an oil-phase is emulsified in water using water-soluble polymers and high shear mixers yielding a stable emulsion at the required droplet size. A water-soluble melamine resin is added and dispersed. The pH is then reduced by the addition of acid initiating the polycondensation which yields cross-linked resins that deposit at the interface between the oil droplets and the water phase. During hardening of the wall material the microcapsules form and the aqueous dispersion of polymer-encapsulated oil droplets is produced.

 

 Liposomes

A liposome is a tiny vesicle generally made from phospholipids which spontaneously form when disrupted in water, with diameter ranging from 25nm to 10microns. Both hydrophobic and hydrophilic active ingredients can be entrapped. The vesicles are made of a bilayer similar to that of a cell membrane hence orient themselves so that the inner and outer phase is hydrophilic. The central core can therefore contain water soluble active ingredients with hydrophobic ingredients being trapped within the bilayer. In a similar way micelles can be formed to entrap hydrophobic materials in the central core. 

 

 Inclusion Complexation

Inclusion complexation involves the use of cyclodextrins which are a group of structurally related natural products formed during bacterial digestion of cellulose (Martin Del Valle, 2004). These cyclic oligosaccharides consist of (α-1,4)-linked α-D-glucopyranose units and contain a lipophilic central cavity and a hydrophilic outer surface. Cyclodextrin inclusion is a molecular phenomenon in which usually a single guest molecule interacts with the cavity of a cyclodextrin molecule to become entrapped and form a stable association. Molecules or functional groups of molecules which are less hydrophilic than water can be included in the cyclodextrin cavity in the presence of water. In order to become complexed, the "guest molecules" should fit, at least partly, into the cyclodextrin cavity. The cavity size as well as chemical modifications to the cyclodextrin defines the affinity of the various guest molecules. In the case of some low molecular weight molecules,

more than one guest molecule may fit into the cavity.  

Physical Microencapsulation Technologies

Spray Coating       Centrifugal Extrusion       Spinning Disk       Annular Jet      Spray Drying       Prilling     Extrusion

 Spray Coating

Coating technologies have been used for many years to prepare pharmaceutical capsules in the traditional macro scale. The particles are tumbled in a pan or other device while the coating material is applied producing capsules we have all used at one time or another. Building on this technique Air-Suspension Coating/Fluidised Bed Coating (a more specific version is called Wurster Coating) of particles by solutions or melts gives better control and flexibility for microcapsule production. Particles of the active ingredient, spheres or granules are coated while suspended in an upward-moving air stream. They are supported by a perforated plate having different patterns of holes inside and outside a cylindrical insert. Just sufficient air is permitted to rise through the outer annular space to fluidize the settling particles. Most of the rising air (usually heated) flows inside the cylinder, causing the particles to rise rapidly. At the top, as the air stream diverges and slows, they settle back onto the outer bed and move downward to repeat the cycle. The particles pass through the inner cylinder many times in a few minutes.

In the food industry the Wurster process has been used to encapsulate/coat vitamins, minerals and functional food ingredients for example to mask an undesirable flavour or improve stability and shelf life. The coating possibilities are relatively unlimited for example it is possible to coat a hydrophilic active ingredient with a hydrophobic polymer, or a hydrophobic active ingredient with a hydrophilic wall material at various thicknesses for process optimisation. With irregular shaped crystals  it is likely that the coated particles would also be irregular in shape, although trials would have to be completed to be certain. Particles can be prepared with potential diameters of less than 50microns upwards.

 

 Centrifugal Extrusion

The centrifugal extrusion process is a liquid co-extrusion process utilising nozzles consisting of concentric orifices located on the outer circumference of a rotating cylinder. A liquid core material is pumped through the inner orifice and a liquid wall material through the outer orifice forming a co-extruded rod of core material surrounded by the wall material. As the device rotates, the extruded rod breaks into droplets which form capsules. The rotational speed affects the capsule size which can be a little as 150microns in diameter and the active ingredients can be encapsulated to up to 80% per weight. Typical wall materials include gelatin, alginate, carageenan, starch, cellulose derivatives, gum arabic, fats and waxes or polyethylene glycol. Flavour oils for example are easily encapsulated using this methodology.

 

 Spinning Disk

Similarly to centrifugal extrusion this spinning disk system uses rotational forces to create droplets. Typically the active ingredient is suspended in a wall material and dropped onto the rotating disk which throws the droplets out towards the circumference of the disk where the wall material solidifies through drying or chilling. As the spinning rate can be carefully controlled the disk process is able to yield narrow particle size distributions, and produce matrix particles of between 5 and 3000 microns.  

 

 

Annular Jet

The technique involves two concentric jets, the inner containing the active ingredient and the outer generally molten wall material which solidifies when exiting the jet. The duel fluid stream naturally breaks into droplets which form the basis of the microcapsule, which depending on configuration can be matrix particles or core-shell in formation. Later adaptations have added a vibrational nozzle to help control the droplet size giving a more uniform product with lower microcapsule sizes down to sub-micron diameters. The liquid can consist of any liquids with limited viscosities e.g. solutions, emulsions, suspensions, melts etc. The soldification can be initiated by any common gelation system (e.g. sol-gel processing, melt) or by using an external additional binder system, (e.g. in a slurry).  

 

 Spray Drying

Traditionally the most common method of microencapsulation of food ingredients. To prepare materials for spray drying the wall material (e.g. maltodextrin, modified starch, gum or a combination of these is hydrated. The flavour or ingredient to be encapsulated is added to the carrier and homogenised or thoroughly mixed using a equivalent technique to create small droplets. Typically the ratio of carrier to flavour would be 4:1, however in some applications higher flavour loads can be used. The mixture is fed into the spray dryer where it is atomised through a nozzle or spinning wheel. Hot air flowing in either a co-current or counter current direction contacts the atomised droplets and evaporates the water producing a matrix particle containing small droplets of flavour. The dried particles are generally collected in a separate chamber through a cyclonic air stream.  

There are many variants of the technique utilising a wide range of wall materials. Spray drying is carried out internally in virtually all major and medium size flavour companies where the encapsulated flavours, spices etc are either sold as spray dried individual active ingredients or as part of a formulated blend.

 

 Prilling

Prilling sometimes called spray chilling, spray cooling or spray congealing is similar to spray drying in that the active ingredient is dispersed in a liquefied coating or wall material and atomised. However in these cases the mixture is atomised into cool or chilled air which solidifies the wall material around the active ingredient. In some cases two fluid nozzles can be used. Microcapsules or matrix particles can be produced generally from 10-400microns in diameter

utilising a wide range of wall materials including waxes, hydrogenated vegetable oils and polymers. This technology has been applied to agrochemicals and drugs but can also be used for flavours and fragrances. As the melting point of the wall material can be carefully selected it is possible to develop control release formulations for a given active ingredient.  

Prilling systems are capable of high throughput for major industrial application and contract manufacture capability is fairly widespread.

 

 Extrusion

Encapsulation by extrusion involves dispersion of the active ingredient in a molten wall material often a carbohydrate such as starch or maltodextrins. The process can also be called melt-extrusion, glass encapsulation, melt-encapsulation or the Durarome process. The mixture is forced through a die producing a solid filament as the material cools in air or by falling into a dehydrating liquid such as isopropyl alcohol. The filaments are then milled and sieved to the desired particle size. Generally the product contains 8-20% flavour load, although the capsules size are in general fairly large (~500microns)

A typical commercially available product range utilises sugar as a wall material and with careful selection of the glass transition temperature can produce glassy matrix particles stable at room temperature which protect the flavours from oxidation. As the coating is sugar based they are particularly suited to sweet applications.

Gel Based Technologies

HydrogelsThe first synthetic Hydrogels were developed in the 1950s and since those days have been researched and developed as food additives, controlled release pharmaceuticals, biomedical implants, tissue constructs for tissue engineering, and  also in regenerative medicines, diagnostics, in the separation of biomolecules or cells, in biosensors, as barrier materials to regulate biological adhesions.

Hydrogels are hydrophilic polymeric network of three dimensional cross linked structures that absorb substantial amount of water. When cross-linked water solubility is reduced because of ionic interaction and hydrogen bonding. It also provides required mechanical strength and physical integrity to the Hydrogels. Hydrogels can absorb water nearly 10-20 times its molecular weight and hence become swollen. Some examples of Hydrogels include contact lenses, wound dressing, and superabsorbents.

The ability to swell can be controlled and used to release active ingredients in a controlled and targeted way. Hydrogels can also be found naturally for example agarose, hylaronan and cellulosic polymers. The materials are biocompatible and easy to modify and release of the active ingredients can be precipitated by change in pH, temperature or even change in the concentration of a specific

substance in the vicinity of the hydrogel.

Conventional Air Freshener Gel SystemsFragrances, insect repellents and other active materials can be controlled released into the environment from gel based systems. Typical air freshener systems are made from cellulose derivatives, carrageen or similar gel matrices and the fragrance is released as the gel dries out on exposure to the air. These gel systems generally contain around 5- 8% fragrance and last a few weeks. The gel is prepared as a liquid and metered into plastic or glass moulds which are sealed ready for use.  

   

 Higher fragrance concentration can be achieved in sodium stearate type gels systems. Typically used in public health applications, these products can contain around 30% fragrance. Although there are specialist gel systems where the fragrance concentration can be higher than 90%.

Plastic Technologies

Fragrances, flavours, insect repellents and other hydrophobic liquid active ingredients can be compounded or infused into a whole variety of plastics for subsequent moulding into consumer and industrial products. The loading in the concentrate is usually around 40% and in final application between 1 and 5%. Anything higher than this is generally uneconomic. In some case finished products can be dipped in the fragrance which is absorbed effectively into the finished product. The active ingredient diffuse out through the surface of the plastic and is released into the atmosphere at a rate which depends on air flow, temperature etc.

Application are very broad and include air fresheners, in car and in the home, gum shields, medical devices (flavoured tongue depressors), infant teething mugs, and even animal toys (chocolate flavoured dog chews).

 

Some specialist systems for adding the active ingredient into plastics are available including liquid injection systems which allow formation of microcapsule within the plastic to further control the release.

 

Natural Preformed Microcapsule Systems

Yeast Microencapsulation TechnologyThe most widely known and commercially available systems utilise yeast cells, either bakers or brewers yeast as preformed microcapsules. The commercial products are usually made up of yeast coated or partially coated with maltodextrin, gelatin or a similar material although purely yeast cell based systems are possible.  They are primarily sold as heat stable flavoured systems for food products, breads, fries etc, although research has been conducted with drugs, pesticides, anti-microbials and many other active ingredients.   As single yeast cell is approximately 8-10microns in diameter and comprises and lipid membrane which provides selectivity for the microencpasulaiton system (only low molecular weight liquid lipophilic active ingredients can be encapsulated successfully) and an outer glucan/mannan cell wall which gives the microcapsule system great strength in process. The active ingredient when mixed under the right conditions diffuse into the yeast cell and remain there until the external conditions promote release, for example when the yeast cell touches a moist mucous membrane, mouth or nose or a strong solvent for the active ingredient.  

 

 

 

 

 

 

 Overall advantages: 

Low cost High Loading

 

Other Natural Systems

Heat Stable Natural

A range of other natural systems have been examined as preformed microcapsules for example spores, pollen grains, starch granules. However, as yet none of these systems have practical applications.