ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 International Journal of Pharma and Bio Sciences PHARMACEUTICS REVIEW ARTICLE MICROENCAPSULATION: A REVIEW JYOTHI SRI.S* 1, A.SEETHADEVI 1, K.SURIA PRABHA 1, P.MUTHUPRASANNA 1 AND ,P.PAVITRA2 1 2 Department Of Pharmaceutics, Hindu College Of pharmacy, Guntur, INDIA. Department Of Pharmaceutics, Shri Vishnu College Of pharmacy, Bhimavaram, INDIA JYOTHI SRI.S Department Of Pharmaceutics, Hindu College Of pharmacy, Guntur, INDIA. ABSTRACT Microencapsulation is the process of surrounding or enveloping one substance within another substance on a very small scale, yielding capsules ranging from less than one micron to several hundred microns in size. The encapsulation efficiency of the microparticles or microsphere or microcapsule depends upon different factors like concentration of the polymer, solubility of polymer in solvent, rate of solvent removal, solubility of organic solvent in water etc. Microencapsulation may be achieved by a myriad of techniques. Substances may be microencapsulated with the intention that the core material be confined within capsule walls for a specific period of time. Alternatively, core materials may be encapsulated so that the core material will be released either gradually through the capsule walls, known as controlled release or diffusion, or when external conditions trigger the capsule walls to rupture, melt, or dissolve. This article is a review of microencapsulation and materials involved in it, morphology of microcapsules, microencapsulation technologies, purposes of microencapsulation, and benefits of microencapsulation, release mechanisms, and application fields, with special emphasis on microencapsulated additives in building construction materials. This article can be downloaded from www.ijpbs.net P - 509 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 KEYWORDS Microencapsulation, morphology, release mechanism, benefits,technologies, applications INTRODUCTION Micro-encapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules. In a relatively simplistic 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. Most microcapsules have diameters between a few micrometers and a few millimeters. The definition has been expanded, and includes more foods. Every class of food ingredient has been encapsulated; flavors are the most common. The technique of microencapsulation depends on the physical and chemical properties of the material to be encapsulated.1 These micro-capsules have a number of benefits such as converting liquids to solids, separating reactive compounds, providing environmental protection, improved material handling properties. Active materials are then encapsulated in micron-sized capsules of barrier polymers (gelatin, plastic, wax ...).2 Many microcapsules however bear little resemblance to these simple spheres. The core may be a crystal, a jagged adsorbent particle, an emulsion, a suspension of solids, or a suspension of smaller microcapsules. The microcapsule even may have multiple walls. MATERIALS INVOLVED MICROENCAPSULATION: IN Microencapsulation is the process by which individual particles or droplets of solid or liquid material (the core) are surrounded or coated with a continuous film of polymeric material (the shell) to produce capsules in the micrometer to millimeter range, known as microcapsules.(Fig.No.1) Figure No.1 Microcapsule with core and coat This article can be downloaded from www.ijpbs.net P - 510 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Core Material: The material to be coated It may be liquid or solid Liquid core may be dissolved or dispersed material Composition of coating material: Drug or active constituent Additive like diluents Stabilizers Release rate enhancers E.g. Coating materials: • G ums: Gum arabic, sodium alginate, carragenan • C arbohydrates: Starch, dextran, sucrose • Celluloses: Carboxymethylcellulose, methycellulose. • L ipids: Bees wax, stearic acid, phospholipids. • P roteins: Gelatin, albumin. Coating Material: Inert substance which coats on core with desired thickness Compatible with the core material Stabilization of core material. Inert toward active ingredients. Controlled release under specific conditions. The coating can be flexible, brittle, hard, thin etc. Abundantly and cheaply available Composition of coating • Inert polymer • Plasticizer • Colouring agent MORPHOLOGY OF MICROCAPSULES: The morphology of microcapsules depends mainly on the core material and the deposition process of the shell. 1- Mononuclear (core-shell) microcapsules contain the shell around the core. 2- Polynuclear capsules have many cores enclosed within the shell. 3- Matrix encapsulation in which the core material is distributed homogeneously into the shell material. - In addition to these three basic morphologies, microcapsules can also be mononuclear with multiple shells, or they may form clusters of microcapsules. (Fig.No.2) Figure. No 2 Morphology of Microcapsules REASON FOR MICROENCAPSULATION AND RELEASE MECHANISM: The reasons for microencapsulation are countless. 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 This article can be downloaded from www.ijpbs.net P - 511 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 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. The reasons for microencapsulation are also described by John Franjione, Ph.D., and Niraj Vasishtha, PhD: as "Microencapsulation is like the work of a clothing designer. He selects the pattern, cuts the cloth, and sews the garment in due consideration of the desires and age of his customer, plus the locale and climate where the garment is to be worn. By analogy, in microencapsulation, capsules are designed and prepared to meet all the requirements in due consideration of the properties of the core material, intended use of the product, and the environment of storage" Different purposes of microcapsule-based final products require different characteristics of microcapsules. The size and shape of microcapsules, chemical properties of microcapsule walls, and their degradability, biocompatibility and permeability have to be considered in the selection of raw materials and microencapsulation processes. The purpose of microencapsulation is usually defined by the permeability. Microcapsules with impermeable walls are used in products where isolation of active substances is needed, followed by a quick release under defined conditions. The effects achieved with impermeable microcapsules include: separation of reactive components, protection of sensitive substances against environmental effects, reduced volatility of highly volatile substances, conversion of liquid ingredients into a solid state, taste and odour masking, and toxicity reduction. On the other hand, microcapsules with permeable walls enable prolonged release of active components into the environment, such as in the case of prolonged release drugs, perfumes, deodorants, repellents, etc., or immobilization with locally limited activity of microencapsulated substances. Examples of later include microencapsulated fertilizers and pesticides with locally limited release to reduce leaching into the ground water, or microencapsulated catalysts and enzymes for chemical and biotechnological processes.(3) The mechanisms of releasing encapsulated materials are planned in advance and depend on the purpose of microencapsulation. An analysis of several hundred patent documents revealed that the first developed and still often used is the mechanism of external pressure which breaks the microcapsule wall and releases the liquid from the core. This principle is applied in pressuresensitive copying papers (pressure of the penball or typewriter head), multi-component adhesives (activation in a press), deodorants and fungicides for shoes (mechanical pressure caused by walking), polishing pastes (rubbing) and aromas and sweeteners in chewing gums (chewing). In some applications, the microcapsule wall breaks because of inner pressure, e.g. for blowing agents in the production of light plastic materials and synthetic leather. In instant drinks, microcapsules dissolve in water.(4) Dissolution at the selected pH value is useful for microencapsulated catalysts and pharmaceuticals. Drugs, vitamins, minerals, essential amino acids, fatty acids, or even whole diets, can be released into the gastro-intestinal tract by enzymatic degradation of digestible microcapsules. The core substance can be released by abrasion of the microcapsule wall, e.g. in antistatic and fragrances for textiles (abrasion in washing machines and dryers), or for grinding and cutting additives. In many applications, core materials are released by heat. Heat-sensitive recording papers (e.g. telefax paper), temperature indicators for frozen food, heat-sensitive adhesives, textile softeners and fragrances in formulations for dryers, cosmetic components to be released at body temperature and aromas for tea and baking, are based on the effect of melting of the microcapsule wall. Microencapsulated fire retardants or This article can be downloaded from www.ijpbs.net P - 512 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 extinguishers, based on release caused by burning of microcapsule walls, are used in fireproof materials. These types of microcapsules are used for wall paper, carpets, curtains, fireprotecting clothes, and added to plastics and coatings for electric devices and wires. Microcapsules in special photographic emulsions, light-sensitive papers and toners for photocopiers are decomposed (or hardened) by light. If the wall is permeable, it slowly releases the content of the core. This mechanism can be applied in controlled drug release products, aromas, fragrances, insecticides and fertilizers. In the case of microencapsulated cells and enzymes in biotechnology, high-molecular weight components can be retained in microcapsules, while low-molecular by-products and substrate residues are extracted through semipermeable microcapsule walls. A special example is that of microencapsulated phase change materials for active accumulation and release of heat in textiles, shoes and building insulation materials. To remain functional over numerous phase transition cycles, they have to remain encapsulated within the impermeable and mechanically resistant microcapsule wall for the whole product life. BENEFITS OF MICROENCAPSULATION: 1Microorganism and enzyme immobilization. - Enzymes have been encapsulated in cheeses to accelerate ripening and flavor development. The encapsulated enzymes are protected from low pH and high ionic strength in the cheese. • The encapsulation of microorganisms has been used to improve stability of starter cultures. 2-Protection against UV, heat, oxidation, acids, bases (e.g. colorant sand vitamins). E.g. Vitamin A / monosodium glutamate 4- Masking of taste or odours. 5- Improved processing, texture and less wastage of ingredients. • Control of hygroscopy • enhance flowability and dispersibility • dust free powder • enhance solubility 6-Handling liquids as solids 7-There is a growing demands for nutritious foods for children which provides them with much needed vitamins and minerals during the growing age. Microencapsulation could deliver the much needed ingredients in children friendly and tasty way. 8- Enhance visual aspect and marketing concept. 9-Today's textile industry makes use of microencapsulated materials to enhance the properties of finished goods. One application increasingly utilized is the incorporation of microencapsulated phase change materials (PCMs). Phase change materials absorb and release heat in response to changes in environmental temperatures. When temperatures rise, the phase change material melts, absorbing excess heat, and feels cool. Conversely, as temperatures fall, the PCM releases heat as it solidifies, and feels warm. 10- Pesticides are encapsulated to be released overtime, allowing farmers to apply the pesticides less amounts than requiring very highly concentrated and toxic initial applications followed by repeated applications to combat the loss of efficacy due to leaching, evaporation, and degradation. 3- Improved shelf life due to preventing degradative reactions (dehydration, oxidation). This article can be downloaded from www.ijpbs.net P - 513 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 11- Ingredients in foods are encapsulated for several reasons. 12- Controlled and targeted release of active • Most flavorings are volatile; therefore ingredients. encapsulations of these components • Many varieties of both oral and extend the shelf-life of these products. injected pharmaceutical formulations are microencapsulated to release over • Some ingredients are encapsulated to longer periods of time or at certain mask taste, such as nutrients added to locations in the body. fortify a product without compromising the product’s intended taste. • Alternatively, flavors are sometimes 13- Microencapsulation allows mixing of incompatible compounds. encapsulated to last longer, as in chewing gum. Figure .No.3 MICROENCAPSULATION TECHNOLOGIES Microencapsulation processes are usually categorized into two groupings: chemical processes5-10 and mechanical or physical processes. These labels can, however, be somewhat misleading, as some processes classified as mechanical might involve or even rely upon a chemical reaction, and some chemical techniques rely solely on physical events. A clearer indication as to which category an encapsulation method belongs is whether or not the capsules are produced in a tank or reactor containing liquid, as in chemical processes, as opposed to mechanical or physical processes, which employ a gas phase as part of the encapsulation and rely chiefly on commercially available devices and equipment to generate microcapsules. There are various techniques available for the encapsulation of core materials.11,12,13 and microencapsulation processes with their relative particle size ranges is mentioned in (Table.No.1) Table.No.1 This article can be downloaded from www.ijpbs.net P - 514 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Microencapsulation Processes with Their Relative Particle Size Ranges PHYSICO - CHEMICAL PROCESSES Coacervation (2 – 1200 um) PHYSICO - MECHANICAL PROCESSES Spray-drying (5 – 5000 um) Polymer-polymer incompatibility (0.5 – 1000 um) Solvent evaporation (0.5 – 1000 um) Encapsulation by supercritical Fluid Encapsulation by Polyelectrolyte multilayer (0.02 – 20 um) Phase Inversion (0.5—5.0 um) Fluidized- bed technology (20 – 1500 um) Pan coating (600 – 5000 um) Hot Melt (1—1000 um) I. PHYSICO CHEMICAL PROCESSES 1. COESERVATION PHASE SEPARATION: A coacervate is a tiny spherical droplet of assorted organic molecules (specifically, lipid molecules) which is held together by hydrophobic forces from a surrounding liquid. Coacervates measure 1 to 100 micrometers across, possess osmotic properties and form spontaneously from certain dilute organic solutions. Their name derives from the Latin coacervare, meaning to assemble together or cluster. They were even once suggested to have played a significant role in the evolution of cells and, therefore, of life itself. Formation In water, organic chemicals do not necessarily remain uniformly dispersed but may separate out into layers or droplets. If the droplets which form contain a colloid, rich in organic compounds and are surrounded by a tight skin of water molecules, then they are known as Coacervates. These structures were first investigated by the Dutch chemist H.G. Bungenberg de Jong, in 1932. A wide variety of solutions can give rise to them; for example, Spinning disc (5 – 1500 um) Co-extrusion (250 – 2500 um) Interfacial polymerization (0.5 – 1000 um) In situ polymerization (0.5 – 1100 um) Coacervates form spontaneously when a protein, such as gelatin, reacts with gum Arabic. They are interesting not only in that they provide a locally segregated environment but also in that their boundaries allow the selective absorption of simple organic molecules from the surrounding medium. In Oparin's view this amounts to an elementary form of metabolism. Bernal commented that they are "the nearest we can come to cells without introducing any biological – or, at any rate, any living biological – substance." However, the lack of any mechanism by which Coacervates can reproduce leaves them far short of being living systems.14 Two methods for coacervation are available, namely simple and complex processes. • In simple coacervation, a desolvation agent is added for phase separation. • Whereas complex coacervation involves complexation between two oppositely charged polymers. Complex coacervation This article can be downloaded from www.ijpbs.net P - 515 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Complex coacervation refers to the phase separation of a liquid precipitate, or phase, when solutions of two hydrophilic colloids are mixed under suitable conditions. The general outline of the processes consists of three steps carried under continuous agitation [15]: Step 1: Formation of three immiscible chemical phases The immiscible chemical phases are (i) a liquid manufacturing vehicle phase (ii) a core material phase and (iii) a coating material phase.(Fig.No.4) To form the three phases, the core material is dispersed in a solution of the coating polymer, the solvent for the polymer being the liquid manufacturing vehicle phase. The coating material phase, an immiscible polymer in a liquid state, is formed by utilizing one of the methods of phase separation coacervation, that is, • By changing the temperature of the polymer solution • By adding a salt • By adding a non-solvent • By adding incompatible polymer to the polymer solution • By inducing a polymer-polymer interaction. Figure .No.4 Process of Coacervation: Step 2: Depositing the liquid polymer coating upon the core material This is accomplished by controlled, physical mixing of the coating material (while liquid) and the core material in the manufacturing vehicle. Deposition of the liquid polymer coating around the core material occurs if the polymer is adsorbed at the interface formed between the core material and the liquid vehicle phase, and this adsorption phenomenon is a prerequisite to effective coating. The continued deposition of the coating material is promoted by a reduction in the total free interfacial energy of the system, brought about by the decrease of the coating material surface area during coalescence of the liquid polymer droplets. Step 3: Rigidizing the coating This is usually done by thermal, cross linking or desolvation techniques, to form a self sustaining microcapsule. Complex coacervation can also occur with the neutralization of two oppositely charged polymers. The core material such as This article can be downloaded from www.ijpbs.net P - 516 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 an oily phase is dispersed in an aqueous solution of the two polymers. A change is made in the aqueous phase (pH) to induce the formation of a polymer rich phase that becomes the wall material. The Coacervates are usually stabilized by thermal treatment, crosslinking or desolvation techniques.(Fig.No.5),They found that the yield of gelatin–acacia microcapsules decreases at surfactant concentrations above or below the optimum. Inhibition of coacervation due to high concentrations of surfactants and disturbance of microencapsulation due to high hydrophilic– lipophilic balance (HLB) values have been reported. In general, the concentration of a surfactant required to increase the yield of microcapsules is too low to produce regularsized droplets. The analysis of the size distribution shows that the microcapsules are multi-dispersed. In the coacervation process, the pH value of a continuous gelatin phase would be adjusted above its isoelectric point to form negatively charged gelatin, which is able to create monodispersed droplets. The positively charged gelatin is attracted to the negatively charged acacia to form coacervate droplets when the pH value is adjusted to below its isoelectric point. Therefore, the particle size distributions of emulsion droplets are effected by the factors of pH adjustment, especially the adding rate of the acidifying agent. The report shows the indomethacin microcapsules had the slowest release rate when the coacervation pH was adjusted to the electrical equivalence pH value and not to the pH of maximum coacervate yield. Gelatin is only stable at the pH value between 4 and 6, our data shown that the alkalization caused the breaking of the wall of the microcapsule made by the crosslinking agent of glycerol. Not only is the purple-colored shikonin alkalized into a blue color, but the saponification effects may also be undergone by the solvent (sesame oil) of extract containing shikonin reacting with sodium hydride. However, this reaction would not be shown in the microcapsule made by the crosslinking agent of formaldehyde. This explains why the shell of the microcapsule made by formaldehyde is more rigid than that made by glycerol. In other words, the microcapsule made by glycerol has a more permeable shell than made by formaldehyde. The particle size of the microcapsule was not affected by the difference of crosslinking agents. Using the low concentration 3% and 6% of plasticizer glycerol instead of formaldehyde, similar morphology results were obtained. Increasing the amount of crosslinking agent leads to an increase in the encapsulation ability. However, the results indicated that above 6% of glycerin, encapsulation ability decreases as the crosslinking agent increases due to the alteration of the mechanism and inability to integrate into the network even after the addition of an excess amount. Figure.No.5 Complex Coacervation This article can be downloaded from www.ijpbs.net P - 517 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 2. POLYMER-POLYMER INCOMPATIBILITY : ( phase separation) • This method utilizes two polymers that are soluble in a common solvent; yet do not mix with one another in the solution. • The polymers form two separate phases, one rich in the polymer intended to form the capsule walls, the other rich in the incompatible polymer meant to induce the separation of the two phases. The second polymer is not intended to be part of the finished microcapsule wall.(Fig.No.6) Figure. No. 6 Polymer-Polymer Incompatibility 3. SOLVENT EVAPORATION: Microencapsulation by solvent evaporation technique is widely used in pharmaceutical industries. It facilitates a controlled release of a drug, which has many clinical benefits. Water insoluble polymers are used as encapsulation matrix using this technique. Biodegradable polymer PLGA (poly (lactic-co-glycolic acid)) is frequently used as encapsulation material.16 Different kinds of drugs have been successfully encapsulated: for example hydrophobic drugs such as cisplatin, lidocaine, naltrexone and progesterone; and hydrophilic drugs such as This article can be downloaded from www.ijpbs.net P - 518 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 solvents like dichloromethane or insulin, proteins, peptide and vaccine. The chloroform with vigorous stirring to form choice of encapsulation materials and the testing the primary water in oil emulsion. of the release of drug have been intensively investigated. However process-engineering • This emulsion is then added to a large aspects of this technique remain poorly reported. volume of water containing an emulsifier To succeed in the controlled manufacturing of like PVA or PVP to form the multiple microspheres, it is important to investigate the emulsion (w/o/w). latter. • The double emulsion is then subjected to Process involved: stirring until most of the organic solvent • Prepare an aqueous solution of the drug evaporates, leaving solid microspheres. (may contain a viscosity building or • The microspheres can then be washed stabilizing agent) and dried.(Fig.No.7) • Then added to an organic phase consisting of the polymer solution in Figure .No. 7 Solvent Evaporation: 4. POLYMER ENCAPSULATION BY RAPID EXPANSION OF SUPERCRITICAL FLUIDS: - Supercritical fluids are highly compressed gases that possess several properties of both liquids and gases. - The most widely used being supercritical CO2 and nitrous oxide (N2O). - - A small change in temperature or pressure causes a large change in the density of supercritical fluids. Supercritical CO2 is widely used for its low critical temperature value, in addition to its nontoxic, non flammable properties; it is also readily available, highly pure and costeffective. This technology also applicable to prepare nanoparticles also.(Fig.No.8) Figure.No8. This article can be downloaded from www.ijpbs.net P - 519 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 RAPID EXPANSION OF SUPERCRITICAL FLUIDS Process Involved: Supercritical fluid contains the active ingredient and the shell material are maintained at high pressure and then released at atmospheric pressure through a small nozzle. The sudden drop in pressure causes desolvation of the shell material, which is then deposited around the active ingredient (core) and forms a coating layer. o Different core materials such as pesticides, pigments, vitamins, flavors, and dyes are encapsulated using this method.17,18,19 o A wide variety of shell materials e.g. paraffin wax and polyethylene glycol are used for encapsulating core substances. o The disadvantage of this process is that both the active ingredient and the shell material must be very soluble in supercritical fluids. 5. HYDROGEL MICROSPHERES: • Microspheres made of gel-type polymers, such as alginate, are produced by dissolving the polymer in an aqueous solution20 • Then, suspending the active ingredient in the mixture • Extruding through a precision device, producing micro droplets • Then fall into a hardening bath that is slowly stirred. The hardening bath usually contains calcium chloride solution.(Fig.No.9) Advantage: The method involves an “all-aqueous” system and avoids residual solvents in microspheres. The particle size of microspheres can be controlled by: o Using various size extruders or o By varying the polymer solution flow rates. Figure.No.9 This article can be downloaded from www.ijpbs.net P - 520 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Hydrogel Microspheres TYPE B: MECHANICAL PROCESS SPRAY-DRYING & SPRAY-CONGEALING: Microencapsulation by spray-drying is a low-cost commercial process which is mostly used for the encapsulation of fragrances, oils and flavors. Spray drying is the continuous transformation of feed from a fluid state into dried particulate form by spraying the feed into a hot drying medium. An emulsion is prepared by dispersing the core material, usually an oil or active ingredient immiscible with water; into a concentrated solution of wall material until the desired size of oil droplets are attained. The resultant emulsion is atomized into a spray of droplets by pumping the slurry through a rotating disc into the heated compartment of a spray drier. There the water portion of the emulsion is evaporated, yielding dried capsules of variable shape containing scattered drops of core material. The capsules are collected through continuous discharge from the spray drying chamber.21This method can also be used to dry small microencapsulated materials from aqueous slurry that are produced by chemical methods. ( Fig. No. 10) Figure .No.10 Spray-Drying Spray congealing can be done by spray drying equipment where protective coating will be applied as a melt. Core material is dispersed in a coating material melt rather than a coating solution. Coating solidification is accomplished by spraying the hot mixture into cool air stream. This article can be downloaded from www.ijpbs.net P - 521 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Waxes, fatty acids, and alcohols, polymers which are solids at room temperature but meltable at reasonable temperature are applicable to spray congealing.22, prepared mucoadhesive micro particles and to design an innovative vaginal delivery systems for econazole nitrate (ECN) to enhance the drug antifungal activity. Seven different formulations were prepared by spraycongealing, a lipid-hydrophilic matrix (Gelucire ((R)) 53/10) was used as carrier and several mucoadhesive polymers such as chitosan, sodium carboxymethylcellulose and poloxamers (Lutrol((R)) F68 and F127) were added. FLUIDIZED-BED TECHNOLOGY: Fluid bed coating, another mechanical encapsulation method, is restricted to encapsulation of solid core materials, including liquids absorbed into porous solids. This technique is used extensively to encapsulate pharmaceuticals. Solid particles to be encapsulated are suspended on a jet of air and then covered by a spray of liquid coating material.23 The capsules are then moved to an area where their shells are solidified by cooling or solvent vaporization. The process of suspending, spraying, and cooling is repeated until the capsules' walls are of the desired thickness. This process is known as the Wurster process when the spray nozzle is located at the bottom of the fluidized bed of particles. Both fluidized bed coating and the Wurster process are variations of the pan coating method The liquid coating is sprayed onto the particles and the rapid evaporation helps in the formation of an outer layer on the particles. The thickness and formulations of the coating can be obtained as desired. Different types of fluid-bed coaters include top spray, bottom spray, and tangential spray (Fig.11). In the top spray system the coating material is sprayed downwards on to the fluid bed such that as the solid or porous particles move to the coating region they become encapsulated. Increased encapsulation efficiency and the prevention of cluster formation are achieved by opposing flows of the coating materials and the particles. Dripping of the coated particles depends on the formulation of the coating material. Top spray fluid-bed coaters produce higher yields of encapsulated particles than either bottom or tangential sprays. The bottom spray is also known as “Wurster’s coater” in recognition of its development by Prof. D.E. Wurster 24. This technique uses a coating chamber that has a cylindrical nozzle and a perforated bottom plate. The cylindrical nozzle is used for spraying the coating material. As the particles move upwards through the perforated bottom plate and pass the nozzle area, they are encapsulated by the coating material. The coating material adheres to the particle surface by evaporation of the solvent or cooling of the encapsulated particle. This process is continued until the desired thickness and weight is obtained. Although it is a time consuming process, the multilayer coating procedure helps in reducing particle defects. The tangential spray consists of a rotating disc at the bottom of the coating chamber, with the same diameter as the chamber. During the process the disc is raised to create a gap between the edge of the chamber and the disc. The tangential nozzle is placed above the rotating disc through which the coating material is released. The particles move through the gap into the spraying zone and are encapsulated. As they travel a minimum distance there is a higher yield of encapsulated particles. Figure. No. 11 This article can be downloaded from www.ijpbs.net P - 522 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 FLUIDIZED-BED TECHNOLOGY PAN COATING: The pan coating process, widely used in the pharmaceutical industry, is among the oldest industrial procedures for forming small, coated particles or tablets. The particles are tumbled in a pan or other device while the coating material is applied slowly. In pan coating, solid particles are mixed with a dry coating material and the temperature is raised so that the coating material melts and encloses the core particles, and then is solidified by cooling; or, the coating material can be gradually applied to core particles tumbling in a vessel rather than being wholly mixed with the core particles from the start of encapsulation.(Fig.No12) Figure.No.12 Pan Coating CENTRIFUGAL EXTRUSION: Centrifugal extrusion processes generally produce capsules of a larger size, from 250 microns up to a few millimeters in diameter. The core and the shell materials, which should be immiscible with one another, are pushed through a spinning two-fluid nozzle. This movement forms an unbroken rope which naturally splits into round droplets directly after clearing the nozzle. The continuous walls of these droplets are solidified either by cooling or by a gelling bath, depending on the composition and properties of the coating material.(Fig.No.13) Figure.No.13 This article can be downloaded from www.ijpbs.net P - 523 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Centrifugal Extrusion A dual fluid stream of liquid core and shell materials is pumped through concentric tubes and forms droplets under the influence of vibration. The shell is then hardened by chemical cross linkings, cooling, or solvent evaporation. Different types of extrusion nozzles have been developed in order to optimize the process(25) SPINNING DISK Suspensions of core particles in liquid shell material are poured into a rotating disc.(26) Due to the spinning action of the disc, the core particles become coated with the shell material. The coated particles are then cast from the edge of the disc by centrifugal force. After that the shell material is solidified by external means (usually cooling). This technology is rapid, cost-effective, relatively simple and has high production efficiencies.(Fig.No.14) Figure.No.14 Spinning Disk Due to the development and specialization of microencapsulation technologies and applications, microencapsulation products differ in structure and terminology: (27) Table.No.2) Table.No.2 This article can be downloaded from www.ijpbs.net P - 524 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Terminology of microencapsulation products Terminology Description Microcapsules (narrow sense of Meaning Products of coating liquid nuclei with solid walls. Nanocapsules Same structure as microcapsules, but smaller. nm Microspheres or Microparticles The cores and walls are both solid. Often, there is no clear distinction between them: the thick solid wall functions as a porous matrix where active substances are embedded. Same structure as microspheres, but smaller. Lipid wall, often made of Phospholipids and cholesterol. Subtypes: unilamellar (one lipid layer) and multilamellar (several lipid layers). Similar to Liposomes but their membranes are made of synthetic amphiphylic molecules (detergents). µm Nanospheres or Nanoparticles Liposomes Niosomes ENHANCING COATING FUNCTIONALITIES WITH MICROCAPSULES Microcapsules can be used in a wide variety of applications [28, 29, 30], since the versatility of microencapsulation technologies offers unlimited combinations of core and shell materials for their production. To date, few investigations have been made into possible applications of Size range µm Schematic illustration nm µm to nm microcapsules in functional coating developments. Microcapsules are applied onto substrates in various ways. For example, they may be sprayed over an existing coating layer, perhaps to provide immediate release of lubricants or perfumes. The most two common process of applying microcapsules in coatings are either to incorporate them into a coating This article can be downloaded from www.ijpbs.net P - 525 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 formulation or by their electrolytic co-deposition with metal ions (Fig. 15) 31, 32 Figure .No 15 Schematic diagram showing pathways for microcapsule incorporation into Coatings. (a) Blending of microcapsules with binders; (b) electrolytic co-deposition of Microcapsules with metallic ions The mixing of microcapsules with coating binders requires compatibility of the shell material with the binder. Generally, microcapsules are used in coatings for controlled-release applications, but microcapsules containing active ingredients such as biocides can also be trapped inside a coating matrix that will release the contents slowly over time. Another interesting example is to use microcapsules in the development of self-healing coatings33. For this, microcapsules containing monomer, cross linker or catalysts are incorporated into a coating matrix such that, when a coating ruptures, the microcapsules along the rupture break open and release their contents. Subsequently, the monomer polymerizes crosslink’s, and fills the damage, thereby preventing further propagation. An innovative example is the use of microencapsulated phase-change material (PCM) particles in interior coatings for buildings 34,35 . During the day, as the temperature rises, the core material melts and stores heat. During the night, when the temperature falls, the heat stored inside the capsules is released, thereby reducing energy needs. Commonly used coat materials in microencapsulation: At Coating Place, coatings are customized to solve problems. Once desired coat functions and coating material restrictions have been established, a coating formulation can be developed from a range of available coating materials, modifiers, and solvents. The list of coating materials shown below represents the range of components that have been successfully applied in coating formulations at Coating Place. This list is not comprehensive; there are many other materials that can be applied. Coating materials may be applied directly as a hot melt or via a solution, suspension, dispersion, emulsion, colloid, or latex. Solvent vehicles may be aqueous or organic. (TABLE.NO.3) Table.No.3 This article can be downloaded from www.ijpbs.net P - 526 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 commonly used coat materials in microencapsulation: S.No 1 2 3 4 5 6 7 8 COMMONLY USED COAT Acacia Acrylic polymers and copolymers Ex: Polyacrylamide Polymethyl methacrylate Agar Albumin Alginates Ex: sodium and calcium alginates Aluminum monostearate Carboxy vinyl polymer MATERIALS 12-hydroxy stearyl alcohol Polyamide Ex: Nylon 6-10 Poly ( ε-caprolactone) Poly dimethyl siloxane Poly vinyl alcohol Shellac Stearic acid Waxes Ex: Bees wax Carnauba wax Spermaceti Paraffin wax Cellulose polymers Ex: cellulose acetate Cellulose acetate phthalate Cellulose acetate butyrate Ethyl cellulose Hydroxy propyl cellulose Hydroxy propyl methylcellulose Methyl cellulose Opadry® coating systems Teflon® fluorocarbons Surelease® systems fluoroplastics Milk solids, Molasses , Nylon, Maltodextrins Shellac, Stearines, Zein APPLICATIONS OF MICROENCAPSULATIONS: In such industrial applications, 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 citric acid in the food coating Kynar® Starches, industry and chemical drugs in the pharma industry and fertilizers in the agro industry. Actually about any area in the industry could beneficiate from microencapsulation technologies. Microencapsulation can be found in various fields (Fig No.16) Figure.No.16. This article can be downloaded from www.ijpbs.net P - 527 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 Applications Of Microencapsulation Cell Immobilization: In plant cell cultures microencapsulation, by mimicking cell natural environment, improves efficiency in production of different metabolites used for medical, pharmacological and cosmetic purposes. Human tissue are turned into bioartificial organs by encapsulation in natural polymers and transplanted to control hormonedeficient diseases such as diabetes and severe cases of hepatic failure. In continuous fermentation processes immobilization is used to increase cell density, productivity and to avoid washout of the biological catalysts from the reactor. This has already been applied in ethanol and solvent production, sugar conversion or wastewater treatment. Beverage Production: Today beer, wine, vinegar and other food drinks production are using immobilization technologies to boost yield, improve quality, change aromas, etc... Protection of Molecules from Other Compounds: Microencapsulation is often a necessity to solve simple problem like the difficulty to handle chemicals (detergents dangerous if directly exposed to human skin) as well as many other molecule inactive or incompatible if mixed in any formulation. Moreover, microencapsulation also allows preparing many formulations with lower chemical loads reducing significantly processes’ cost. Drug Delivery: After designing the right biodegradable polymers, microencapsulation has permitted controlled release delivery systems. These revolutionary systems allow controlling the rate, duration and distribution of the active drug. With these systems, microparticles sensitive to the biological environment are designed to deliver an active drug in a sitespecific way (stomach, colon, specific organs). One of the main advantages of such systems is to protect sensitive drug from drastic environment (pH,) and to reduce the number of drug administrations for patient. Quality and safety in food, agricultural & environmental sectors: Development of the “biosensors” has been enhanced by encapsulated bio-systems used to control environmental pollution, food cold chain (abnormal temperature change). Soil Inoculation: This article can be downloaded from www.ijpbs.net P - 528 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 For example Rhizobium is a very interesting bacterium which improves nitrate adsorption and conversion. But inoculation is often unsuccessful because cells are washed out by rain. By cell encapsulation processes, it is possible to maintain continuous inoculation and higher cell concentration. This list is not exhaustive, the nutraceuticals’ world could be the last mentioned because of the growing interest & increasing demand we have to face in ingredients with health benefits which often require improvement of their efficiency and stability (e.g. probiotics, vitamins...) by protecting and offering targeting release of the active materials. Applications of microcapsules in building construction materials An analysis of scientific articles and patents shows numerous possibilities of adding microencapsulated active ingredients into construction materials, such as cement, lime, concrete, mortar, artificial marble, sealants, paints and other coatings, and functionalized textiles. A summary of applications is presented in (Fig.No.17) Figure .No.17 Applications of microcapsules in building construction materials This article can be downloaded from www.ijpbs.net P - 529 ISSN 0975-6299 Vol 3/Issue 1/Jan – Mar 2012 FUTURE PROSPECTS OF MICROENCAPSULATION o Microencapsulation, as its name suggests, is the creation of a tiny capsule (or, in practice, lots of tiny capsules), usually just microns in diameter, containing a particular material. In practice, microencapsulation entails placing a spherical shell composed of a synthetic or natural polymer completely around another chemical. That shell delays or slows the release of the core material. When the polymer shell dissolves or is ruptured by pressure, the material it encapsulates is released. o Microencapsulation is not new. It has been around for decades in the form of spray drying, spray chilling, freeze drying and coacervation. But scientists believe that the sector has innovated rapidly. The microencapsulation sector is therefore fast establishing itself at the cutting edge of food and beverage flavor development. The use of nanotechnology, which involves the study and use of materials at sizes of millionths of a millimeter, could increasingly be used in the creation and development of flavors and flavor systems in the future. o Microencapsulated flavors are opening up new food development possibilities never before attempted “The Franken food that o o o o improves you” in UK’s. Of these, encapsulation technologies play a huge role in their picture of the future of foods. Microencapsulation of oil ingredients, like omega-3, with sugar beet pectin could provide an alternative to more traditional encapsulating agents like milk proteins and gum Arabic Further research of microencapsulation, to test the oxidative stability of the microcapsules over time as well as flavor retention for aroma compounds. Future prospects of microencapsulation of islets of Langerhans used sodium alginate and poly-l-lysine (PLL) to form the capsules In addition to the familiar uses noted above, microcapsules have found uses in the pharmaceutical, agricultural, cosmetic, and food industries and have been used to encapsulate oils, aqueous solutions, alcohols, and various solids. ACKNOWLEDGEMENTS We acknowledged our management of Hindu college of pharmacy and also very much thankful to Professors A.SeethaDevi, K.Suria Prabha, and P.MuthuPrasanna for giving constant support. REFERENCES 1. 2. 3. Jackson L. S, Lee K, "Microencapsulation and the food industry", Lebensmittel Wissenschaft Technologie, Retrieved 199102-02. Remuñán C, Alonso MJ,Microencapsulation de medicamento, En.Vilá-Jato, JL.Tecnología Farmacéutica,Aspectos fundamentales de los systems farmacéuticos operaciones básicas, Madrid: Ed. Síntesis, SA:577-609,(1997). Boh.B, Kornhauser, A.Dasilva,Microencapsulation for pollution 4. 5. 6. 7. prevention, developing support for introducing clean(er) pp: 205-222, (1996). Boh, B., Sajovic, I., Voda, K.: Microcapsule applications: patent and literature analysis pp:85-156,(2003) J.L. Luna-Xavier, E. Bourgeat-Lami, A. Guyot, Colloid. Polym. Sci:279,947–958, (2001) W.F. Liu, Z.X. Guo, J. Yu, J. Appl. Polym. Sci: 97(4), 1538–1544, (2005). M. Okubo, H. Minami, Y. Jing, J. Appl ,Polym. Sci:89, 706–710, (2003). This article can be downloaded from www.ijpbs.net P - 530 ISSN 0975-6299 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. Vol 3/Issue 1/Jan – Mar 2012 M.L.Soto-Portas, J.F. Argillier, F. Méchin,N. Zydowicz, Polym. Int: 52,522– 527, (2003). B.Z. Putlitz, K. Land fester, H. Fischer, M. Antonietti, Adv. Mater :13(7), 500–503,( 2001). A.J.P. van Zyl, R.D. Sanderson, D. de WetRoos, B. Klumperman, Macromolecules: 36, 8621–8629,( 2003). S. Benita, Microencapsulation:Methods and Industrial applications, Marcel Dekker, Inc, New York, (1996). R.Arshady, Microspheres, Microcapsules and Liposomes, Citrus Books, London, United Kingdom, (1999). M.W.Ranney,Microencapsulation Technology, Noyes Development Corporation, Park Ridge: 275(1969). Stephen J. Dick, “The Biological Universe”: pg.340(1999). Leon Lachman, Herbert A. Lieberman, Joseph L. Kanig,“The Theory and Practice of Industrial Pharmacy”, 3rd edition, pp.420. Mahmoud M. Ghorab a, Hossein Zia a, Louis A. Luzzi a, Preparation of controlled release anticancer agents I: 5-fluorouracilethyl cellulose microspheres, Journal of Microencapsulation, 7(4), October: p 447 – 454(1990). R. Ghaderi, A Supercritical Fluids Extraction Process for the Production of Drug Loaded Biodegradable Microparticles, PhD Thesis, ACTA Universitatis Upasaliensis, Uppsala, (2000). H. Liu, M.Z. Yates, Langmuir:18, 6066– 6070(2002). P. Chambon, E. Cloutet, H. Cramail, Macromolecules:37, 5856–5859(2004). Sankar.C,Mishra.B,Development and in vitro evaluations of gelatin A microspheres of ketorolac tromethamine for intranasal administration.Acta Pharm: 53(2): 101-10, (2003). Desai, K. G. H.1 Park, H. J.2, Preparation of cross-linked chitosan microspheres by spray drying: Effect of cross-linking agent on the properties of spray dried microspheres, Journal of Microencapsulation: 22(4), June, p. 377395(19),( 2005). 22. Albertini B, Passerini N, Di Sabatino M, Vitali B, Brigidi P, Rodriguez L, Polymerlipid based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate, Eur J Pharm Sci, Dec 25,( 2008 ). 23. K. Lehmann, in: Microcapsules and Nanoparticles in Medicine and Pharmacy (Ed. M. Donbrow), CRC Press, Boca Raton :pp. 73–97,( 1992). 24. D.E. Wurster, US Patent 2648609, and September 8, through, Swapan Kumar Ghosh, Functional coatings and Microencapsulation: A General Perspective:P 22. (1953) 25. J.T. Goodwin, G.R. Somerville, Chemtech:623–626,( 1974). 26. R.E. Sparks, M. Norbert, US Patent 4675140, June 6, (1987). 27. Boh, B. Kornhauser, A., Dasilva, E Microencapsulation technology applications: with special reference to biotechnology: pp. 51-76,(1996). 28. R. Arshady, Microspheres, Microcapsules and Liposomes, Citrus Books, London, United Kingdom, (1999). 29. G.O. Fanger, Chemtech: 397–405,(1974). 30. H. Yoshizawa, KONA: 22, 23–31,(2004) 31. A. Dietz, M. Jobmann, G. Raf ler, Mat.wiss. u. Werkstofftech, 31, 612–615,(2000). 32. Z. Liqun, Z. Wei, L. Feng, J. Mater. Sci: 39, 495–499,( 2004). 33. E.N. Brown, S.R. White, N.R. Sottos, J.Mater. Sci: 39, 1703–1710,( 2004). 34. J.F. Su, L.X. Wang, L. Ren, J. Appl.Polym. Sci: 97(5), 1755–1762,( 2005). 35. M.N.A. Hawlader, M.S. Uddin, H.J. Zhu,Int. J. Energy Re: 26, 159–171,(2002). This article can be downloaded from www.ijpbs.net P - 531