INTERNATIONALE PHARMACEUTICA SCIENCIA

| Jan-March 2011 | Vol. 1 | Issue 1 | Available online http://www.ipharmsciencia.com 2011 IPS

REVIEW ARTICLE

Microencapsulation as a novel drug delivery system

ABSTRACT
An appropriately design novel drug delivery system can be a major advance for solving the problems related towards the release of the drug at specific site with specific rate. Novel drug delivery systems have various advantages over other conventional drug therapy. In which microencapsulation is one approach for achieving the novel drug delivery dosage forms such as sustained release and controlled release. The main objective of this article is take a look at microencapsulation as a novel drug delivery system as it provide the protection, taste masking, alteration in absorption site, and prolonging the drug release as required. Key words: Microencapsulation, dosage form, absorption, target site. Kumar Ankit*, Sharma Pramod Kumar and Banik Arunabha Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology NH-58, Bypass Road, Baghpat Crossing, Meerut-250005, UP, INDIA Date of Submission: 22-01-2011 Date of Acceptance: 12-03-2011 Conflict of interest: Nil Source of support: None

INTRODUCTION Microencapsulation is the process in which small droplets or particles of liquid or solid material are surrounded or coated by a continuous film of polymeric materials. [1] Firstly the microencapsulation procedure was discovered by Bungen burg de Jon and Kan in 1931and which were deal with the preparation of gelatin spheres and use of a gelatin coacervation process. The controlled drug delivery system has used to reduce the problems associated with conventional therapy and to improve the therapeutic efficacy of a given drug. The maximum therapeutic efficacy can be achieved by delivering of the active agent in the optimal rate to the target tissue, then causing little toxicity and minimum side effects.
[2]

nature and they have the particle size below 200 m. [3] Microencapsulation process helps for converting the liquids to solids, changing the colloidal and surface properties, providing environmental protection and controlling the release characteristics of different coated materials. Some of these properties can be achieved by macropakaging techniques but in microencapsulation the small coated particles are used and used to make to a wide variety of dosage forms and has not been feasible.
[4]

Novel drug delivery systems

which were initiate with the course of optimizing the bioavailability by the modification of the bioavailability of the drug concentration in blood.
[5,6]

With the

sustained and controlled release products, drug therapy can be improved that is the common goal achieved over with their non sustained and controlled release with the same drug.
[7]

To deliver a

therapeutic substance to the target site in a sustained controlled release fashion various approaches are used. One is by using microspheres as carriers for drugs. Microspheres are considered as free flowing powders consisting of polymers which are biodegradable in
Address for correspondence Ankit Kumar, Research Scholar (M. Pharm), Department of Pharmaceutical Technology, MIET, NH-58, Bypass Road, Baghpat crossing, Meerut 250005, U.P. INDIA Email Id: ankit.dahar@gmail.com 1

Microencapsulated

products (micro particles) are the small entities that have an active agent know as the core material surrounded by a shell known as the coating material or embedded into a matrix structure. Most Microparticle shells are of organic polymers, but waxes and lipids are also used. Generally the size of the microencapsulated products (microparticles) is considered as larger than 1
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Kumar Ankit, et al: Microencapsulation as a novel drug delivery system

micrometer and up to 1000 micrometers in diameter. Commercially available microparticles contained 1090% w/w core. A number of core materials can be encapsulated like that live cells, adhesives, flavors, agrochemicals, enzymes, pharmaceuticals. [8] The more recent result of pharmaceutical research is that the absorption rate of a drug can be controlled by controlling its rate of release from the dosage form .The controlled released dosage forms are so designed and formulated as having the sustained action, sustained release, prolonged action, delayed action and timed release medication.
[9]

also may be enteric coated, soft gelatin capsules, or suspensions in liquids, all of these allow dispersion of individual microcapsules on release. Reasons for Microencapsulation The main reason for microencapsulation is for sustained or prolonged release of the drug. This technique has been widely used for masking the organoleptic properties like taste and odor of many drugs and thus improves patient compliance e.g. Paracetamol, nitrofurantoine for masking the bitter taste. By using microencapsulation techniques the liquid drugs can be converted in a free flowing powder. The drugs can be protected by microencapsulation which is sensitive to moisture light and oxygen, such as nifedipine is protected from photo instability. Microencapsulation technique also helpful to prevent the incompability between drugs The drugs which are volatile in nature may vaporize at room temperature like Aspirin and peppermint Reduction oil in can be and prevented GI by microencapsulation. toxicity irritation including with KCL and ferrous sulphate can be achieved by microencapsulation Microencapsulation has also been employed to change the site of absorption. This application has been useful for those drugs which have the toxicity at lower pH. Bakan and Anderson were reported that microencapsulated vitamin A palmitate had enhanced stability, as prevent from oxidation. Microencapsulation method has also been employed to prepare intrauterine contraceptive device. [15] Mechanism and Kinetics of Drug Release Major mechanisms of drug release from microcapsules
[16]

This has been done by

developing the new drug entities, discovering of new polymeric materials that are suitable for prolonging the drug release, safety, improvement in therapeutic efficacy. [10]

(a)

(b)

Fig. 1: Scanning electron micrographs of (a) mononuclear, (b) multinuclear microspheres The scanning electron microscopy is used to reveal the structural features of microcapsules as these are to be vary and complex. The walled prototype may be mononuclear as shown in Figure 1(a) or may have multiple core structure.
[11]

And there may also be

[12]

double or multiple concentric coating present.

As

aggregated microcapsules have an additional external wall and thus very in shape and size Fig. 1(b). Although, the microstructure of membrane and interior can be detected by SEM of surfaces or sections and their physical quality is not easily characterized quantitatively in microcapsules as involving the measurements of porosity, tortuousity and crystallinity, but there is some progress has been made and efforts are to calculate porosity and permeability from release data, densities, dimensions, and core/wall ratios. [13,14] The standard pharmaceutical dosage forms are employed, like that hard gelatin capsules, which
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include diffusion, dissolution, osmosis and erosion: DiffusionDiffusion is the most common
2

1.

mechanism of drug release (core material) in which the

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Kumar Ankit, et al: Microencapsulation as a novel drug delivery system

dissolution fluid penetrates the shell then the core material comes into the contact with the dissolution fluid and leak out through the interstitial channels or pores. [17] Basically, the release of core material depends on (1)the rate of drug dissolution in the dissolution fluid, (2) the rate of penetration of dissolution fluid to the microcapsules and (3) the rate at which the dissolved drug escape from the microcapsule.
[18]The

release. However, based on various studies concerning with the release characteristics, the following considerations can be made1) Drug release rate from microcapsules follow the zero order kinetic. 2) Microcapsules of monolithic type have the t1/2 dependant release rate for the first half of the total drug release and thereafter turn down exponentially. 3) Microcapsules of monolithic type having large excess of dissolved drug, the release rate are t1/2 dependant throughout almost the entire drug release. The path traveled by drug is not constant in monolithic capsules; as the drug at the center travels a large distance than the drug at the surface. Therefore, the release rate in monolithic capsules generally decreases with time. Materials for Microencapsulation Core Materials: The specific material to be coated by using the specific coating material 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 materials. The solid core material can be active constituents, stabilizers, diluents, and release-rate inhibitors or accelerators. This variation in the core material composition provides definite flexibility and utilization of this characteristic then allows effective design and development of the preferred microcapsule properties. [4] Coating Materials: The material to be coated on the core material should be capable of forming a film that is cohesive with the core material, chemically compatible with other materials and nonreactive with the core material .The coating materials provide the desired coating Properties such as Strength, flexibility, impermeability, optical properties, and stability. Criteria for selection coating material: That would be depending upon review of existing literature where as practical use of free-film information based on following reasons: 1) Cast or free films that prepared by the using casting techniques that will formed a thicker
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kinetics of

such drug release follows Higuchis equation [19] Q = [D/J (2A CS) CS t]

Here, Q is the amount of drug released per unit area of exposed surface in time t; J is the tortuousity of the capillary system in the wall; D is the diffusion coefficient of the solute in the solution; A is the total amount of drug per unit volume; is the porosity of the wall of microcapsule; CS is the solubility of drug in permeating dissolution fluid. 2. Dissolution- The release rate of drug from the microcapsule depends on the dissolution rate of polymer coat, when the coat is soluble in the dissolution fluid.
[20] [17]

The solubility in the dissolution

fluid and thickness of coat influence the release rate. 3. Osmosis- Another method of drug release is through osmosis. The essential requirement of osmosis is semi permeable membrane and in microcapsule polymer coat serve the purpose. As the process progress an osmotic pressure is created between the outside and inside membrane of microcapsule which result in release of drug through small pores. 4. Erosion- Erosion of coat generally occur due to pH or enzymatic hydrolysis and causes drug release alcohol and glyceryl monostearate. The drug release from microcapsules has become complicated forms of because of great diversity in physical microcapsules with size, shape
[22, 23] [21]

with certain coat materials like bees wax, stearyl

and The

arrangement of the core and coat materials.

physiochemical properties of core materials like solubility, diffusibility and partition coefficient and of coating materials like variable porosity, thickness and inertness which makes difficult to modeling of drug
3

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Kumar Ankit, et al: Microencapsulation as a novel drug delivery system

film microencapsulation as compared by using of small particles that will formed a thin microencapsulation; hence its proved that cast films may not be extrapolate to the thin microcapsule coatings. 2) The coating properties can be affected by the coating substrate of core material. Hence, the result and classic free film data depend on the selection of coating material. [4] Table 1: Example of coating materials [2]
Water soluble resins Gelatin Starch Polyvinylpyrrolidone Water insoluble resins Ethyl cellulose Polyethylene Polyamide Waxes and resins Paraffin Beeswax Stearicacid Stearyl alcohol Enteric resins Shellac Cellulose acetate phalate Zein

temperature of the supporting air stream. The process variables that can affect the process- [24] 1) 2) 3) 4) 5) Concentration of the coating material or if in Solubility, surface area, density, melting point Application rate of coating material. Temperature of air stream. The amount of air required to fluidize the core solution form then melting point. volatility, volatility of core material.

material. Coacervation Phase Separation: This process of microencapsulation is generally referred to The National Cash Register (NCR) Corporation and the patents of B.K. Green. This process consists of three steps- [25] Formation of three immiscible phases; a liquid manufacturing phase, a core material phase and a coating material phase Microencapsulation Methods [24] Air suspension Coacervation phase separation Multiorifice-centrifugal process Spray drying and congealing Pan coating Solvent evaporation techniques Polymerization Deposition of the liquid polymer coating on the core material Rigidizing of the coating material Step-1: The first step of coacervation phase separation involves the formation of three immiscible chemical phases: a liquid vehicle phase, a coating material phase and a core material phase. The three phases are formed by dispersing the core material in a solution of coating polymer, the vehicle phase is used as a solvent for polymer. The coating material phase consists of a polymer in a liquid phase, is formed by using one of the of phase separation- coacervation method, i.e. .by changing the temperature of the polymer solution, by adding a solution, or by inducing a polymer- polymer interaction. [24] Step-2: It involves the deposition of the liquid polymer coating upon the core material. This is done by controlled mixing of liquid coating material and the core material in the manufacturing vehicle. The liquid coating polymer deposited on the core material if the polymer is adsorbed at the interface formed between the core material and liquid phase. The reduction in the total free interfacial energy of the system help to promote the deposition of the coating material,
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Hydroxyethylcellulose Polymethacrylate

Air Suspension: The air suspension technique involves the dispersion of the core materials in a supporting air stream and the spray coating on the air suspended particles. The moving air stream suspends the particles on an upward within the coating chamber. The design of the coating chamber and its operating parameters should be in such a way that could effect the flow of the particles through the coating zone of chamber, where a coating material (polymer solution) is applied to the moving particles. As the moving particles passed through the coating zone repeatedly, the core material receive more of coating material. The cyclic process is repeated about several time depending on the coating thickness desired or whether the core material particles are thoroughly encapsulated. The encapsulated product is dried by passing the stream air. Drying rates are directly depending to the
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Kumar Ankit, et al: Microencapsulation as a novel drug delivery system

brought by the decrease of the coating material surface area during coalescence of the liquid polymer droplets.
[25]

Pan Coating: The microencapsulation of larger particles by pan methods has been used in the pharmaceutical industry. This method is generally used for solids. In microencapsulation, for effective coating the size of solid particles should be more than 600 microns and this process has been used for the preparation of controlled release beads. Medicaments are coated onto various spherical substrates such as nonpareil sugar seeds with various polymers. In the coating pan, the coating is applied as an atomized spray onto the core material. In this the hot air is passed over the coated materials to remove the coating solvent in coating pan. [24] Spray Drying and Spray congealing: Spray drying and spray congealing methods have been used as microencapsulation techniques for many years. Spray drying and spray congealing processes have some similarities because both involve dispersing the core material in a liquefied coating substance and spraying or introducing the core coating mixture into some environmental condition, in which rapid solidification of the coating is effected. The main difference between the two methods is by which coating solidification is completed. In the case of spray drying the coating solidification is effected by rapid evaporation of a solvent in which the coating material is dissolved. In spray congealing method the coating solidification is completed by thermally or by solidifying the dissolved coating by introducing the core material mixture into a nonsolvent. Removal of the nonsolvent from the coated product is then accomplished by sorption, evaporation or extraction techniques. [27] Solvent Evaporation: Solvent evaporation techniques are performed in a liquid manufacturing vehicle (O/W emulsion) which is formed by agitation of two immiscible liquids. In this process microcapsule coating (polymer) is dissolved in a volatile solvent, which is immiscible with the liquid manufacturing vehicle phase. A core material to be microencapsulated is dispersed in the coating polymer solution. To obtain the microcapsule of appropriate size the core and coating material mixture is dispersed in the liquid manufacturing vehicle phase with agitation. The agitation of system is constant till the solvent
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Step-3: In the last step rigidizing of the coating material done by the thermal, cross linking desolvation techniques, to forms a self supporting microcapsule.
[24]

Microencapsulation by coacervation phase separation process Multi orifice-Centrifugal process:

Microencapsulation by the multi orifice-centrifugal process is the mechanical process in which the centrifugal force is applied to throw a core material particle through an enveloping microencapsulation membrane. The factors affect the Process include the rotational speed of the cylinder, the flow rate of the coating and core materials and the concentration, viscosity and surface tension of the core material. This process is capable of producing the microencapsulation of the liquids and solids of varied size ranges, by applying the different coating materials. The encapsulated product can be supplied as slurry in the hardening media. With this process the production rate of 50 to 75 pounds per hour have been achieved.
[24]

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partitions into the aqueous phase and aqueous phase is removed by evaporation. Various process variables that could affect the process of microencapsulation include methods of forming dispersions, evaporation rate of the solvent for the coating polymer, temperature cycles and agitation rates. Important factors that must be considered when preparing microcapsules by solvent evaporation techniques include choice of vehicle phase and solvent for the polymer coating, as these choices greatly influence microcapsule properties as well as the choice of solvent recovery techniques .This technique to produce microcapsules is applicable to liquid and solid core

material. Water soluble or water insoluble materials are used as core materials. A variety of film forming polymers can be used as coating materials. [24] Polymerization: Polymerization is a new method of microencapsulation to form protective microcapsule coatings in situ. Microencapsulation by polymerization involved reaction between a core material substance and continuous phase in which the core material is dispersed. In polymerization a liquid or gaseous phase is used as continuous or core material and as a result the polymerization reaction occurs at a liquid-liquid, solid-liquid, Liquid-gas, or solid-gas interface. [24]

Table 2: Examples of some microencapsulated drugs [2]

Active moiety Aspirin Paracetamol Islet of Langerhans Isosorbide dinitrate Progesterone Menthol Potassium chloride Urease Vit.A Palmitate Nifedipine Characteristic Property Slightly soluble in water Slightly soluble in water Viable cells Water soluble Slightly soluble in water Volatile solution Highly soluble in water Water soluble enzyme Nonvolatile liquid Practically insoluble in water Purpose of encapsulation Taste masking, sustained release, reduced in gastric irritation, Taste masking Sustained normalization of diabetic condition Sustained release Sustained release Reduction in volatility, Sustained release Reduction in gastric irritation Perm selectivity of enzyme, substrate and reaction Stabilization to oxidation Prevention from photoinstability Final product form Tablet or capsule Tablet Injection Capsule Varied Lotion Capsule Dispersion Dry powder Dry powder

Conclusion:

The

microencapsulation

approach

not in the stomach. Therefore, this safe and efficient particular system should be developed in future. Acknowledgement: Authors are highly thanks full to Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology for providing necessary guidance and facilities to carry out literature survey. References:
1. 2. 3. 4. http://www.gate2tech.org. Jain N K., Controlled and Novel drug delivery. CBS Publisher, 1997, pp 236-237. Vyas S P, Khar R K. Targeted and Controlled drug delivery. CBS Publisher, 2002, pp 418. Leon L, Herbert A L, Joseph L K. The Theory and Practice 5. of Industrial Pharmacy. Varghese Publishing House, 1990, pp 412- 428. Khawla A, Abu izza, Lucila Garcia-Contreras, Robert Lu D. Selection of better methed for the preparation Vol 1 Issue 1 6

offers a wide variety of opportunities such as protection and masking, reduced dissolution rate, facilitation of handling, and spatial targeting of the active ingredient. This approach facilitates accurate delivery of small quantities of potent drugs, reduced drug concentrations at sites other than the target organ or tissue and protection of labile compounds before system and after administration and prior over to the appearance at the site of action. Microencapsulation offers potential advantages conventional drug delivery systems. Microspheres and microparticales are a unique carrier system for various pharmaceuticals dosage form. Hence, microspheres and microparticales are not only used for controlled release but also for the target delivery of the drug to the specific site in to the body. The microencapsulation approach also beneficial for those drugs which required to dissolved in to the intestine
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Kumar Ankit, et al: Microencapsulation as a novel drug delivery system of microspheres by applying hierarchy process. Journal of Pharm Sci 1996;85:144-149. 6. Khawla A, Abu izza, Lucila Garcia-Contreras, Robert Lu D . Selection of better methed for the preparation of microspheres by applying hierarchy process. Journal of Pharm Sci 1996 ; 85:572-575. 7. Jian You, Fu-de Cui, Xu Han, Yongsheng Wang, Lei Yang, 8. Kreitz Ying-Wei M, Yu, Qing-po. L, Literature Mathiowitz of E. 22. Biointerfaces, 2006; pp 35-41. Brannon-peppas Microencapsulation Encyclopedia of 493-553. 9. 10. Banker G S, Rhodes C T. Modern pharmaceutics. In Parma Publication, 2002; 121: 501-527. Gohel MC, Amin AF. Formulation optimization of controlled release diclofenac sodium microspheres using factorial design. J CONTROL RELEASE 1998; 51:115-122. 11. Jegat C, Taverdet J L. Stirring speed influence study on microencapsulation process and the drug release from microcapsules. Polymer Bulletin 2000, 44: 345351. 12. Benita S, Donbrow M. Controlled drug delivery through microencapsulation, Journal of Pharm Sci 1982; 71: 205210. 13. Nikhil K Sachan. Controlled drug delivery through microencapsulation. University( 2005)1-3. 14. Reis MAA, Sinisterra RD, Belchior JD. An alternative approach based on artificial neural networks to study controlled drug release. Journal of Pharmaceutical Sciences 2004; 93: 418430. 15. 16. James S: Encyclopedia of Pharmaceutical Technology .Third Edition, 1325-1333. Brazel SC, Peppas NA. Modeling of drug release from swellable polymers. Eur J Pharm Biopharm, 2000; 49: 4748. 17. Korsmeye RW, Gurny R, Doelker EM, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics 1983; 15: 2535. 18. Gunder W, Lippold BH, Lippold BC. Release of drugs from ethyl cellulose microcapsules (diffusion pellets) with pore formers and pore fusion. Euro J Pharm Sci, 1995; 3: 203214. 19. Higuchi T: Mechanism of sustained action medication, theoretical analysis of rate of release of Assam India, Dibrugarh 25. 24. 23. controlled 21. solid drugs dispersed in solid matrices. Journal of Pharmaceutical Sciences 1963; 52: 11451149. 20. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. European Journal of Pharmaceutical Sciences 2001; 13: 123133. Sachacht E, Van Bos M: Potential developments in hydrogel gastrointestinal delivery systems. Topics in Pharmaceutical Sciences Amsterdam. Elsevier Science Publishers B.V .1987. Nokhodchi A, Zakeri-Milani P, Valizadeh H and Hassan-Zadeh D: Evaluation of microcapsules of acetyl salicylic acid prepared with cellulose acetate phthalate, ethyl cellulose or their mixtures by an emulsion non-solvent addition technique Ars Pharmaceutical 2002; 43: 135147. Haznedar S, Dortue B. Preparation and in vitro evaluation of eudragit microspheres containing acetazolamide. Int J of Pharm 2004; 269: 131140. Lachman LA, Liberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. Varghese Publishing House, 1990, pp 414-420. ODonnell PB, McGinity JW. Preparation of microspheres by solvent evaporation technique. Adv Drug Del Rev 1997; 28:25-42.

drug delivery. John Wiley Sons publishers, 1999, pp

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