Microencapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules, of many useful properties. In general, it is used to incorporate food ingredients, enzymes, cells or other materials on a micro metric scale. Microencapsulation can also be used to enclose solids, liquids, or gases inside a micrometric wall made of hard or soft soluble film, in order to reduce dosing frequency and prevent the degradation of pharmaceuticals. In a relatively simple form, a microcapsule is a small sphere with a uniform wall around it. The material inside the microcapsule is referred to as the core, internal phase, or fill, whereas the wall is sometimes called a shell, coating, or membrane. Some materials like lipids and polymers, such as alginate, may be used as a mixture to trap the material of interest inside. Most microcapsules have pores with diameters between a few micrometers and a few millimeters. The coating materials generally used for coating are:
The definition has been expanded, and includes most foods, where the encapsulation of flavors is the most common. The technique of microencapsulation depends on the physical and chemical properties of the material to be encapsulated.
Many microcapsules however bear little resemblance to these simple spheres. The core may be a crystal, a jagged adsorbent particle, an emulsion, a Pickering emulsion, a suspension of solids, or a suspension of smaller microcapsules. The microcapsule even may have multiple walls.
core-forming space available to permanently or temporarily entrapped substances. Note: The substances can be drugs, pesticides, dyes, and similar materials.
- 1 Reasons for encapsulation
- 2 Techniques to manufacture microcapsules
- 2.1 Physical methods
- 2.2 Physicochemical methods
- 2.3 Chemical methods
- 3 Release methods and patterns
- 4 Applications
- 5 References
- 6 Bibliography
- 7 External links
Reasons for encapsulation
The reasons for microencapsulation are countless. It is mainly used to increase the stability and life of the product being encapsulated, facilitate the manipulation of the product and control its liberation in an adequate time and space. In some cases, the core must be isolated from its surroundings, as in isolating vitamins from the deteriorating effects of oxygen, retarding evaporation of a volatile core, improving the handling properties of a sticky material, or isolating a reactive core from chemical attack. In other cases, the objective is not to isolate the core completely but to control the rate at which it leaves the microcapsule, as in the controlled release of drugs or pesticides. The problem may be as simple as masking the taste or odor of the core, or as complex as increasing the selectivity of an adsorption or extraction process. In environmental science, a pesticide may be microencapsulated to minimize leaching or volatilization risks.
Techniques to manufacture microcapsules
This process widely used in the pharma industry, is the oldest industrial procedure for forming small, coated particles or tablets. The particles are tumbled in a pan or other device.
Liquids are encapsulated by a rotating head containing concentric nozzles. In this process, a jet of core liquid is surrounded by a sheath of wall solution or melt.
Core-shell encapsulation or microgranulation (matrix-encapsulation) can be done using a laminar flow through a nozzle and an additional vibration of the nozzle or the liquid. The vibration has to be done in resonance with the Rayleigh instability and leads to very uniform droplets. The liquid can consist of any liquids with limited viscosities (0-10,000 mPa·s have been shown to work), e.g. solutions, emulsions, suspensions, melts etc. The soldification can be done according to the used gelation system with an internal gelation (e.g. sol-gel processing, melt) or an external (additional binder system, e.g. in a slurry). The process works very well for generating droplets between 20–10,000 μm (0.79–393.70 mils), applications for smaller and larger droplets are known. The units are deployed in industries and research mostly with capacities of 1–20,000 kg per hour (2–44,000 lb/h) at working temperatures of 20–1,500 °C (68–2,732 °F) (room temperature up to molten silicon). Heads are available with from one up to several hundred thousand nozzles.
Spray drying serves as a microencapsulation technique when an active material is dissolved or suspended in a melt or polymer solution and becomes trapped in the dried particle. The main advantages are the ability to handle labile materials because of the short contact time in the dryer and the operation is economical. In modern spray dryers the viscosity of the solutions to be sprayed can be as high as 300 mPa·s. Applying this technique, along with the use of supercritical carbon dioxide, sensitive materials like proteins can be encapsulated.
Coacervation-phase separation consists of three steps carried out under continuous agitation.
- Formation of three immiscible chemical phases: liquid manufacturing vehicle phase, core material phase and coating material phase.
- Deposition of coating: core material is dispersed in the coating polymer solution. Coating polymer material coated around core. Deposition of liquid polymer coating around core by polymer adsorbed at the interface formed between core material and vehicle phase.
- Rigidization of coating: coating material is immiscible in vehicle phase and is made rigid. This is done by thermal, cross-linking, or dissolution techniques.
In interfacial polycondensation, 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. A solution of the pesticide and a diacid chloride are emulsified in water and an aqueous solution containing an amine and a polyfunctional isocyanate is added. Base is present to neutralize the acid formed during the reaction. Condensed polymer walls form instantaneously at the interface of the emulsion droplets.
Interfacial cross-linking is derived from interfacial polycondensation, and was developed to avoid the use of toxic diamines, for pharmaceutical or cosmetic applications. In this method, the small bifunctional monomer containing active hydrogen atoms is replaced by a biosourced polymer, like a protein. When the reaction is performed at the interface of an emulsion, the acid chloride reacts with the various functional groups of the protein, leading to the formation of a membrane. The method is very versatile, and the properties of the microcapsules (size, porosity, degradability, mechanical resistance) can be customized. Flow of artificial microcapsules in microfluidic channels:
In situ polymerization
In a few microencapsulation processes, the direct polymerization of a single monomer is carried out on the particle surface. In one process, e.g. cellulose fibers are encapsulated in polyethylene while immersed in dry toluene. Usual deposition rates are about 0.5μm/min. Coating thickness ranges 0.2–75 μm (0.0079–2.9528 mils). The coating is uniform, even over sharp projections. Protein microcapsules are biocompatible and biodegradable, and the presence of the protein backbone renders the membrane more resistant and elastic than those obtained by interfacial polycondensation.
In a number of processes, a core material is imbedded in a polymeric matrix during formation of the particles. A simple method of this type is spray-drying, in which the particle is formed by evaporation of the solvent from the matrix material. However, the solidification of the matrix also can be caused by a chemical change.
Release methods and patterns
Even when the aim of a microencapsulation application is the isolation of the core from its surrounding, the wall must be ruptured at the time of use. Many walls are ruptured easily by pressure or shear stress, as in the case of breaking dye particles during writing to form a copy. Capsule contents may be released by melting the wall, or dissolving it under particular conditions, as in the case of an enteric drug coating. In other systems, the wall is broken by solvent action, enzyme attack, chemical reaction, hydrolysis, or slow disintegration.
Microencapsulation can be used to slow the release of a drug into the body. This may permit one controlled release dose to substitute for several doses of non-encapsulated drug and also may decrease toxic side effects for some drugs by preventing high initial concentrations in the blood. There is usually a certain desired release pattern. In some cases, it is zero-order, i.e. the release rate is constant. In this case, the microcapsules deliver a fixed amount of drug per minute or hour during the period of their effectiveness. This can occur as long as a solid reservoir or dissolving drug is maintained in the microcapsule.
A more typical release pattern is first-order in which the rate decreases exponentially with time until the drug source is exhausted. In this situation, a fixed amount of drug is in solution inside the microcapsule. The concentration difference between the inside and the outside of the capsule decreases continually as the drug diffuses.
Nevertheless, there are some other mechanisms that may take place in the liberation of the encapsulated material. These include, biodegradation, osmotic pressure, diffusion, etc. Each one will depend on the composition of the capsule made and the environment it is in. Therefore, the liberation of the material may be affected by various mechanisms that act simultaneously.
The applications of micro-encapsulation are numerous. The ones mentioned below are some of the most common ones.
- Carbonless copy paper
- E-paper or e-ink
- Essential oils, flavors and other volatile bioactives for food or in feed additives
- Pharmaceuticals, small molecules and recently also peptides and small proteins for oral or sublingual delivery
- Phase change materials
- Self-healing material such as novel plastics that can automatically repair damage:
- Temperature release (controlled release) in baking
- Thermochromic dyes
- Time release technology for pharmaceuticals
- Visual indicators
- Self healing coatings
- DNA protection from degradation for product tracing and data storage
- Protection of bioactive compounds that are easily degradated under normal environmental conditions.
- Singh, M. N.; Hemant, K. S.; Ram, M; Shivakumar, H. G. (2010). "Microencapsulation: A promising technique for controlled drug delivery". Research in Pharmaceutical Sciences. 5 (2): 65–77. PMC 3093624. PMID 21589795.
- Mervosh, T.L.; EW Stoller; FW Simmons; TR Ellsworth; GK Sims (1995). "Effects of starch encapsulation on clomazone and atrazine movement in soil and clomazone volatilization". Weed Science. 43 (3): 445–453. doi:10.1017/S0043174500081455.
- "Medical Dictionary: Enteric coating". Freedictionary.com. Retrieved 9 February 2009.
- Barba, A.A.; d'Amore, M.; Chirico, S.; Lamberti, G.; Titomalino, G. (2009). "A general code to predict the drug release kinetics from different shaped matrices". European Journal of Pharmaceutical Sciences. 36 (2–3): 359–368. doi:10.1016/j.ejps.2008.10.006. PMID 19022380.
- Hedaoo, Rahul K.; et al. (2014). "Fabrication of Core–Shell Novel Polyurea Microcapsules Using Isophorone Diisocyanate (IPDI) Trimer for Release System". International Journal of Polymeric Materials and Polymeric Biomaterials. 63 (7): 352–360. doi:10.1080/00914037.2013.845191.
- Puddu, M.; Paunescu, D.; Stark, W. J.; Grass, R. N. (2014). "Magnetically Recoverable, Thermostable, Hydrophobic DNA/Silica Encapsulates and Their Application as Invisible Oil Tags". ACS Nano. 8 (3): 2677–2685. doi:10.1021/nn4063853. PMID 24568212.
- Grass, R. N.; Heckel, R.; Puddu, M.; Paunescu, D.; Stark, W. J. (2015). "Robust Chemical Preservation of Digital Information on DNA in Silica with Error-Correcting Codes". Angewandte Chemie International Edition. 54 (8): 2552–2555. doi:10.1002/anie.201411378. PMID 25650567.
- Aizpurua-Olaizola, Oier; Navarro, Patricia; Vallejo, Asier; Olivares, Maitane; Etxebarria, Nestor; Usobiaga, Aresatz (2016-01-01). "Microencapsulation and storage stability of polyphenols from Vitis vinifera grape wastes". Food Chemistry. 190: 614–621. doi:10.1016/j.foodchem.2015.05.117. PMID 26213018.
- Prakash, S. et al. "The Gut Microbiota and Human Health with an Emphasis on the Use of Microencapsulated Bacterial Cells", Journal of Biomedicine and Biotechnology (2011),
- Brandau, T (2002). "Preparation of monodisperse controlled release microcapsules". Int. J. Pharm. 242 (1–2): 179–184. doi:10.1016/S0378-5173(02)00151-5.