Objectives of microcapsules:

It has some special objectives like:

1. It alters the surface characteristics of the particles to significant extent.

2. Microencapsulation also can be used for the sustained release or prolonged-action medication.

3. It can be used to taste-masked tablets, powder, suspensions.

4. It has proved that this technique is new for formulation in creams, ointments, aerosols, suppositories, and injectable.

5. Select appropriate shell formulation from FDA-approved, GRAS (generally recognized as safe) materials.

6. Selecting the most effectible process to provide the desired morphology, stability, and release mechanism.

7. Economic feasibility of large-scale production, operating and other miscellaneous expenses, such as transportation cost, regulatory cost, and downtime losses [8]

Classification:

Microcapsules can be classified on three basic categories according to their morphology as follows,

1. Mononuclear.

2. Polynuclear.

3. Matrix types.

4. Multi-wall.

5. Irregular.

In mononuclear (core-shell) the microcapsules contain the shell around the core, In polynuclear capsules have many cores enclosed within the shell, while matrix encapsulation, 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 as shown in fig.no. 2 [4]

Fig.2: The morphological Classification of Microencapsulation

Coating Material used in Microencapsulation:-

Table No:1 Synthetic Polymer

Sr. No	Type of synthetic polymer	Example
A.	Non-biodegradable	PMMA
		Acrolein
		Glycidyl methacrylate
		Epoxy polymers
B.	Biodegradable	Lactides and glycolides and their copolymers
		Polyalkyl cyano acrylates

Table No:2 Natural Material

Sr. No	Example
1	Agarose
2	Proteins
3	Albumins
4	Gelatin
5	Collagen
6	Carbohydrates
7	Starch ,

Table No:3 Different Microencapsulation Technique

Sr. No	Microencapsulation Technique	Physical nature of the core material	Particle size (Micrometer)
1	Polymerization	Solid and Liquid	1-1000
2	Interfacial Polycondensation	Solid and Liquid	3-2000
3	Coacervation		2-5000
4	Solvent evaporation	Solid and Liquid	5-5000
5	Air Suspension	Solid	35-5000
6	Pan coating	Solid	600-5000
7	Spray drying and congealing	Solid and Liquid	600
8	Multiorifine centrifugation	Solid and Liquid	1-5000

1. Polymerization:

A relatively new microencapsulation method utilizes polymerization techniques to from protective microcapsule coating particular substance. This methods involve the reaction of monomeric units located at the interface form between a core material substance while continuous phase in which the core material is dispersed. The continuous or core material supporting phase is in a liquid or gas form, and hence the polymerization reaction occurs at a liquid, liquid-gas, solid-liquid, interface[10]

2. Solvent Evaporation/Solvent Extraction:

Microcapsule formation by solvent evaporation or solvent extraction 53-60 is very similar to suspension crosslinking, but in this case the polymer is usually hydrophobic polyester. The polymer is dissolved into the water immiscible volatile organic solvent like as dichloromethane or chloroform, into which the core material is also dissolved or dispersed. The final solution is added drop wise to a continuous stirring aqueous having a suitable stabilizer like poly (vinyl alcohol), to form small polymer droplets containing encapsulated material. The droplets are resist to produce the corresponding polymer microcapsules [3]. This resisting process is accomplished by the removal of the solvent from the polymer droplets by solvent evaporation as well as by solvent extraction (with a third liquid which is a precipitant for the polymer and miscible with both water and solvent) This method produces microcapsules with higher porosities than those obtained by solvent evaporation of microencapsulation by solvent evaporation technique. Solvent evaporation or extraction processes is useful for the formulation of drug loaded microcapsules based on the biodegradable polyesters such as polylactide, (lactideco - glycolide) and polyhydroxybutyrate [4]

3. Air Suspension:

Also known as Wruster process, consist of the dispersing of solid, particulate core materials in a supporting air stream and the spray coating of the air suspended particles Air-suspension coating of particles by solutions or melts gives better control and flexibility. The particles 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 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. Process variables that affect the encapsulation: Density, surface area, melting point, solubility, volatility, crystallinity and flowability of the core material. Coating material concentration. Coating material application rate. Volumes of air required to support and fluidize the core material. Amount of coating material required. Inlet and outlet operating temperature. The process has the capability of applying coating in the form of solvent solutions, aqueous solutions, emulsions, dispersions or hot melts. In regard to particle size, the air suspension technique is applicable to both microencapsulation and macro-encapsulation coating processes.[6]

Fig no.3: Diagrammatic representation of Wruster process

4. 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. With respect to microencapsulation, solid particles greater than 600 microns in size are generally considered essential for effective coating, and the process has been extensively employed for the preparation of controlled - release beads. Medicaments are usually coated onto various spherical substrates such as nonpareil sugar seeds, and then coated with protective layers of various polymers Generally the coating is applied as a solution, or as an atomized spray, to the desired solid core material in the coating pans. To remove the coating solvent, warm air is passed over the coated materials as the coatings are being applied in the coating pans. In some cases, final solvent removal is accomplished in a drying oven.[6]

Fig 4: Representation of a typical pan coating

5. Spray drying and spray congealing:

Spray drying and spray congealing methods have been used for many years as microencapsulation techniques. Because of certain similarities of the two processes, they are discussed together. Spray drying and spray congealing processes are similar in that both involve dispersing the core material in a liquefied coating substance and spraying or introducing the core coating mixture into some environmental condition, whereby relatively rapid solidification of the coating is effected [15]. The principal difference between the two methods, for purpose of this discussion, is the means by which coating solidification is accomplished. Coating solidification in the case of spray drying is effected by rapid evaporation of a solvent in which the coating material is dissolved. Coating solidification in spray congealing method however is accomplished by thermally congealing a molten coating material or b solidifying a dissolved coating b introducing the coating core material mixture into a nonsolvent. Removal of the nonsolvent or solvent from the coated product is ten accomplished by sorption extraction or evaporation techniques [2]

Fig.no 5: A typical spray drying structure

6.multiorific-centrifugal process:

The Southwest Research Institute (SWRI) has developed a mechanical process for producing microcapsules that utilizes centrifugal forces to hurl a core material particle trough an enveloping [18]

microencapsulation membrane thereby effecting mechanical microencapsulation. Processing variables include the rotational speed of the cylinder, the flow rate of the core and coating materials, the concentration and viscosity and surface tension of the core material. The multiorifice-centrifugal process is capable for microencapsulating liquids and solids of varied size ranges, with diverse coating materials. The encapsulated product can be supplied as slurry in the hardening mediaor s a dry powder. Production rates of 50 to75 pounds per our have been achieved with the process.[10]

Recent advances in microencapsulation processes:

1 Fluidized bed spray coating

2 Deagglomerating jet spray coating

3 Melt prilling in fluidized bed

4 Using ultrasonic atomizer based on interfacial solvent

exchange

5 Miscellaneous

1.Fluidized bed spray coating:

Microencapsulation of core particles that can be fluidized by a gas may be accomplished by spraying a coating agent (wall) onto the surface of the particles. The wall may be formed by congealing of a molten material, by chemical reaction on the surface or by evaporation of a solvent from a coating solution. The solvent is removed with the gas leaving the bed. Coating thickness may be easily controlled by the amount of wall material applied. Conventional fluidized-bed spray-coating methods are generally employed in the encapsulation of solid particles. Liquids may be encapsulated if they can be frozen inparticulate form and coated at temperatures below their freezing point. Fluidized-bed encapsulation has yielded such products as: slow release fertilizer, coated iron particles, seeds, salts, and clays [15]

Fig.no 6: Fluidized bed spray coating

2) De-agglomerating jet spray coating:

Numerous modifications of the conventional fluidized-bed microencapsulation concept have been developed to satisfy the needs of particular problems. A de-agglomerating jet unit was created to coat core particles of small size which tend to agglomerate in a conventional fluidized bed, by application of a high velocity gas jet and a conical conduit in a fluidized bed to de-agglomerate the partially coated particles before additional coating material is applied from the coating spray nozzle. This method may be employed to encapsulate solid particles down in the 10-g size range. It does not lend itself to liquid cores nor to solid core particles larger than about 300 g. Products including pharmaceuticals, resin catalysts, inorganic salts, and pigmented plastics.

3) Melt prilling in fluidized bed:

In this process the wall material must be in solid particle form so that it can be fluidized by a gas. The core material is heated and is in liquid form for atomization from a nozzle to yield droplets of the desired size. The droplets of core material fall into the fluidized bed and are simultaneously cooled and coated with the wall material particles. The heat liberated from the core droplets is transferred to the wall material particles causing them to melt, adhere to the core surface, and flow together to form a coherent capsule wall structure. A mixture of capsules and bed material is removed from the fluidizing column and the capsules are separated by screening. The excess bed material is returned to the system. The process has been made continuous by providing continuous capsule removal and bed material make-up Both liquid and solid core capsules can be made; however, the core material must be able to withstand the temperature required to provide the energy for fusing the wall material particles together. Applications of this process have yielded slow-release glycerin capsules, and biologically active encapsulated products.

Fig.no 7: Melt prilling in fluidized bed

4) Using ultrasonic atomizer based on interfacial solvent exchange:

In this method, reservoir-type microcapsules were generated using a dual micro-dispenser system that involves two inkjet nozzles. Series of drops of polymer solution and aqueous drug solution are separately produced using ink-jet nozzles, and then they are induced to collide in the air [15]. Following the collision, the two liquid phases are separated as a core and a membrane within the merged micro-drops due to the surface tension difference of the two liquids. Recently, it was found that a coaxial ultrasonic atomizer can also be utilized to generate reservoir-type microcapsules under the similar principle, yet, in a simple, mild, and highly efficient manner. This method is successfully used for microencapsulation of therapeutic proteins

5) Miscellaneous:

a) Meltable dispersion: In this method the wall material in a molten state and the core material are dispersed in a medium (in which both are insoluble) at a temperature high enough to maintain the wall material in liquid form. By means of agitation and use of wetting agents the wall material is caused to envelop the core particles and solidifies on cooling to complete capsule formation [17].

b) Diffusional exchange: In this process, previously formed capsule with a porous coating is immersed in a preferred liquid so that the original core contents are diffused out of the capsule and the liquid diffused in. The resulting encapsulated liquid is then over-coated or subjected to a treatment that imparts the desired degree of wall impermeability.

Table No:4) Various microencapsulation techniques and the processes involved in each technique [2]:-

Sr. No	Microencapsulation technique	Major steps in encapsulation
1	Spray-drying	a. Preparation of the dispersion b. Homogenization of the dispersion c. Atomization of the infeed dispersion. Dehydration of the atomized particles
2	Spray-chilling	a. Preparation of the dispersion b. Homogenization of the dispersion c. Atomization of the infeed dispersion
3	Spray-cooling	a. Preparation of the dispersion b. Homogenization of the dispersion c. Atomization of the infeed dispersion
4	Fluidized-bed coating	a. Preparation of coating solution b. Fluidization of core particles. c. Coating of core particles
5	Coacervation	a. Formation of a three-immiscible chemical phases b. Deposition of the coating. Solidification of the coating

Basic consideration of microencapsulation technique:

Microencapsulation often involves a basic understanding of the general properties of microcapsules, Such as the nature of the core and coating materials, the stability and release characteristics of the coated materials and the microencapsulation methods [16]. The intended physical characters of the encapsulated product and the intended use of the final product must also be considered [21].

a. Core material:

The core material, defined as the specific material to be coated, can be liquid or solid in nature. The composition of the core material can be varied as the liquid core can include dispersed and/or dissolved material. The solid core can be a mixture of active constituents, stabilizers, diluents, excipients and release rate retardants or accelerators.

b. Coating materials:

The coating material should be capable of forming a film that is cohesive with the core materials, be chemically compatible and nonreactive with the core material and provide the desired coating properties such as strength, flexibility impermeability, optical properties and stability. The total thickness of the coatings achieved with microencapsulation techniques is microscopic in size [17].

c. Stability, release and other properties:

Three important areas of current microencapsulation application are the stabilization of core materials, the control of the release or availability of core materials and separation of chemically reactive ingredients within a tablet or powder mixture. A wide variety of mechanisms is available to release encapsulated core materials; such as disruption of the coating can occur by pressure, shear or abrasion forces, permeability changes brought about enzymatically etc., improved gastro tolerability of drugs can be obtained by microencapsulation.[16]

d. Physical character of the final product:

Microcapsules should have desirable physical properties like ability to flow, to be compacted or to be suspended and the capsule wall must be capable of resisting the pressure during compression etc.

e. coating materials:

A number of different substances both biodegradable as well as non-biodegradable have been investigated for the preparation or microcapsules. These materials include the polymers of natural and synthetic origin and also modified natural substances. Some of the polymers used in the preparation of the microcapsules are classified and listed below.[5]

Need of Microencapsulation:-

1. To achieve sustained or prolonged drug release.

2. To mask unpleasant taste and odor of drugs to improve patient compliance.

3. Environment sensitive drugs can be stabilized by this technique. Bakan and Anderson reported that microencapsulated vitamin A palmitate had enhanced stability.3

4. Microencapsulation can be used for converting liquid drugs into free flowing powders.

5. Drug-drug and drug-excipient incompatibility can be prevented by microencapsulation.

6. Vaporization of volatile drugs such as methyl salicylate and peppermint oil can be prevented.

7. Alteration in site of absorption can also be achieved by microencapsulation.

8. Reduction in toxicity and GI irritation caused by various drugs can be possible.

9. Toxic chemicals such as insecticides may be microencapsulated to reduce possibility of sensitization of factorial person [21].

Application of Microencapsulation:-

Some of the applications of microencapsulation can be described as given below:

1. Prolonged release dosage forms. The microencapsulated drug can be administered, as microencapsulation is perhaps most useful for the preparation of tablets, capsules or parenteral dosage forms.

2. Microencapsulation can be used to prepare enteric coated dosage forms, so that the medicament will be

3. It can be used to mask the taste of bitter drugs.

4. From the mechanical point of view, microencapsulation has been used to aid in the addition of oily medicines to tableted dosage forms. This has been used to overcome problems inherent in producing tablets from otherwise tacky granulations [17]. This was accomplished through improved flow properties. For example, the nonflowable multicomponent solid mixture of niacin, riboflavin, and thiamine hydrochloride and iron phosphate may be encapsulated and made directly into tablets.

5. It has been used to protect drugs from environmental hazards such as humidity, light, oxygen or heat. Microencapsulation does not yet provide a perfect barrier for materials, which degrade in the presence of oxygen, moisture or heat, however a great degree of protection against these elements can be provided. For example, vitamin A and K have been shown to be protected from moisture and oxygen through microencapsulation [16].

6. The separations of incompatible substances, for example, pharmaceutical eutectics have been achieved by encapsulation. This is a case where direct contact of materials brings about liquid formation. The stability enhancement of incompatible aspirin-chlorpheniramine maleate mixture was accomplished by microencapsulating both of them before mixing [17]

Factors Influencing Encapsulation Efficiency:-

The encapsulation efficiency of the microparticle or microcapsule or microsphere will be affected by different [14]

parameters:

1. High solubility of the polymer in organic solvent.

2. Low solubility of organic solvent in water.

3. Low concentration of polymer.

4. High DP/CP ratio.

5. Low solvent removal rate results in slow solidification of microparticles and low encapsulation efficiency.

6. Low solubility of the polymer in organic solvent.

7. Solubility of organic solvent in water.

8. High concentration of polymer. High solvent removal rate gives fast solidification of microparticles and high encapsulation efficiency.

CONCLUSION:

Microencapsulation is one of the quality preservation techniques of sensitive substances and a method for production of materials with new valuable properties. Microencapsulation is process of enclosing micron sized particles in a polymeric shell. Significances of microencapsulation For Sustained or prolonged drug release For Masking test and odor of many drugs Converting liquid into free flowing properties Drugs which are sensitive to Light, oxygen, moisture they are easily stabilized. Microencapsulation technologies are applied in any area of the industry. It can be found in: Cell immobilization, Beverage production, Protection of molecules from other compounds, Drug delivery, Quality and safety in food, agricultural and environmental sectors, pharmaceuticals etc.

ACKNOWLEDGEMENT:

According to my study and about microencapsulation, it is a very innovative technique for the different point of view such as the boosting of drug stability, purity, bioavailability and potency in well manner. For avoiding the excessive drug administration and minimized the adverse effect if drug this type of technique are mainly modified. By the survey of different literature the microencapsulation technique is confidential as well as effective technique. Significance of this method in various type of industry is probably in large amount and profitable to industry. Some time for increase the patient compliance this technique is used. So all over observation and study view microencapsulation technique is useful in various types of industry and our daily routing.

REFERENCES:

1. Methavee Peanparkdee, Satoshi Iwamotoa, Ryo Yamauchi, 2016. Microencapsulation: A review of applications in the food and pharmaceutical industries. Reviews in Agricultural Science, Volume 4, page no.56.

2. A Poshadri and Aparna Kuna 2010. Microencapsulation Technology: A review. J.Res. Angrau, 38(1)86-102, Page no 86.

3. Sanjay Kumar Das, Sheba Rani Nakka David, Rajan Rajabalaya, 2011. Microencapsulation technique and its partial. In. J. Pharma Sic Tech, Volume 6, Page no 1.

4. Loveleen Preet Kaur, Sheenam Sharma, Tarun Kumar Guleri, 2013. Microencapsulation: A new era in novel drug delivery. International Journal of Pharmaceutical Research and Bio Science, Volume 2.

5. K.P. Sampath Kumar, Tejbe. Sk, Shameem Banu, P. Naga Lakshmi, D. Bhowmik, 2013 Microencapsulation Technology; Indian Journal of Research in Pharmacy and Biotechnology, Volume 1 Page 324.

6. Talat Farheen, Azmat Shaikh, Sadhana Shahi, 2017. A Review on a Process: Microencapsulation. International Journal of Pharma Research and Health Sciences, volume 5, page no 1823.

7. N. Venkata Naga Jyothi, P. Muthu Prasanna, Suhas Narayan Sakarkar, K. Surya Prabha,2010. Microencapsulation techniques, factors influencing encapsulation efficiency. Journal of Microencapsulation, volume 27(3), page no 87.

8. S.K. Gupta, I.J. Singhvi, M.K. Shirsat, G. Karwani, A. Agarwal, Aditi, 2011. Microencapsulation techniques and its application in pharmaceutical field. Asian Journal of Pharmaceutical Sciences and Clinical Research; Volume 1, page no 67.

9. Pablo Teixeira da Silva I, Leadir Lucy Martins Fries I, Cristiano Ragagnin de MenezesI,2014. Microencapsulation: concepts, mechanisms, methods and some applications in food technology; Ciência Rural, Santa Maria, volume 44, page no 1304.

10. P. Venkatesan, R. Manavalan and K. Valliappan,2009. Microencapsulation: a vital technique in novel drug delivery system. Journal of Pharmaceutical Science and Research; Volume 1, page no 26.

11. Ying Lu, Kinam Park, 2012. Microencapsulation: Methods and Pharmaceutical Applications. Encyclopedia of Pharmaceutical Science and Technology, Volume1 page no 1.

12. O’Donnell PB, Mc Ginity JW, 1997. Preparation of microspheres by solvent evaporation technique. Advanced Drug Delivery Reviews. V0lume 4, page no 25-42.

13. Hashidzume A, Ohara T, Morishima Y, 2002. Coacervation of hydrophobically modified polyanions by association with nonionic surfactants in water. Langmuir.

14. Ramington GA, 2006. The Science and Practice of Pharmacy. BI Publication, Volume 1, page no 924.

15. Lachman LA, Liberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. Mumbai, India: Varghese Publishing House;3:414-415.

16. Ramington GA. The Science and Practice of Pharmacy. Delhi, India: BI Publication; 2006, 21st Edition, Volume I, Page no 924.

17. Leon L, Herbert AL, Joseph LK. Theory and practice of industrial pharmacy, Varghese Publishing House, 3^rd Edition, 1990: 412-429. 18. Herman N. Microencapsulation techniques Applications and Problems, Journal of the Society of Cosmetic Chemists, Page no.85-98.

18. Rodrigues, R.A.F and Grosso, C.R.F, 2008. Cashew gum microencapsulation protects the aroma of coffee extracts. Journal of Microencapsulation, Volume 25, page no 13–20.

19. Schlameus, W. 1995. Centrifugal extrusion encapsulation: Encapsulation and Controlled Release of Food Ingredients. Risch, S.J.; Reineccius, American Chemical Society: Washington, DC, 1995.

20. Indian Pharmacopoeia, 3rd Ed. Delhi: Controller of Publications, 1996, vol. II, p A7.

21. Lulwah Y. Al-Furaih, Ibtisam M. Ababutain, Azzat B. Abd-El-Khalek, Ahmed M. Abdel-Salam, 2016. Effect of different microencapsulation materials on stability of Lactobacillus plantarum DSM 20174. African Journal of Biotechnology, Volume 15, Page no 1207.

Received on 26.04.2020 Modified on 18.05.2020

Research J. Science and Tech. 2020; 12(3):201-210.

DOI: 10.5958/2349-2988.2020.00028.5