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MICROENCAPSULATION: ADVANCEMENTS IN TECHNOLOGY AND ITS PATENTS

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About Authors:
Arsh Chanana*, Mahesh Kumar Kataria, Ajay Bilandi
Department of Pharmaceutics, Seth. G.L. Bihani S.D. College of Technical Education,
Sri Ganganagar (Rajasthan) INDIA
*arshchanana806@gmail.com

Abstract-
Microcapsule is a tiny sphere including core material/internal phase or fill, coated with/surrounded by wall know as shell, coating or membrane. The usual size range of the microcapsule lies between 1 to 1000 μm. The technique is usually applied for targeted drug delivery, protection of the molecule and stability if the core material. Microencapsulation system offers potential advantages over conventional drug delivery systems and also established as unique carrier systems for many pharmaceuticals. This article contains the traditional and the recent techniques, including their patents, for the preparation of microcapsules. Solvent exchange method, coacervation, polymerization, hot melts etc are several recent techniques are used for the preparation of the microcapsules. The microencapsulation technique, as Novel drug Delivery System (NDDS), is widely applied for delivery of probiotics, drugs, pesticide, food etc. Although significant advances have been made in the field of microencapsulation, still many challenges need to be rectified during the appropriate selection of core materials, coating materials and process techniques.

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REFERENCE ID: PHARMATUTOR-ART-1916

Introduction-
It is a process in which tiny particles or droplets are surrounded by a coating to give small capsules various useful properties. A microcapsule is a tiny sphere with a uniform wall around it. The inside material in microcapsule is referred to as the core, internal phase or fill, whereas the wall is sometimes called a shell, coating or membrane. This process produces small particles ranging in size from 1 to 1000 μm. It is a one of the most intriguing filed in the area of drug delivery system. Microencapsulation includes bioencapsulation which is more restricted to entrapment to the entrapment of a biologically active substance (from DNA to entire cell or groups of cells) generally to improve its performance & enhance its shelf life. The microencapsulation study would be encouraged with the motto “Small is better”.

Microcapsule Terminology & Basic Structures-
There are basically two phase of microcapsules. The upper phase called the wall, external phases coating or shell and the inner phase called core, as contain active material, internal phases or payload according to the formulation. The Microcapsules are of various types according to the arrangement of the core and the coating material. The simple microcapsules contain a single external phases where as it double in the case of double walled. In multi-core the internal phase is two or more. In matrix types the internal phase is mixed with the external phases. In particulate the active medicament is mixed in external phases and in the irregular type of microcapsules there are irregular structures of the microcapsule.

Figure No. 1:  Basic Structure & Type of Microcapsule

Various Techniques used for MICROENCAPSULATION
Microencapsulation is a process where the particles of an active agent are surface coated to provide change in the physicochemical properties of an active agent. Several processing techniques (Table No. 1) are used to prepare microencapsules depending on the desired properties of the final product, the properties of the agent being coated and the coating material.

Table No 1: Different Micro-encapsulation Techniques

Physical methods

Physico-chemical methods

Other methods

 Pan coating

Ionotropic gelation

Emulsion Solidification

Air-suspension coating

Coacervation

1.  Simple coacervation

2. Complex coacervation

Solvent evaporation

Centrifugal extrusion

Solvent extraction

Solvent Exchange

Vibrational Nozzle

Chemical methods

Hot-Melt Microencapsulation

Spray–drying

1. Fluid-bed coating (Air-suspension technique)

2. Pan coating

Interfacial polycondensation

 

Interfacial cross-linking

 

In-situ polymerization

 

Matrix polymerization

 

Conventional Microencapsulation Techniques
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. Relatively large particles can be encapsulated by pan coating. Size of solid particles should be greater than 600 mm to achieve effective coating using this method. This is a typical method used to apply sugar coatings on candies. This method employs a rotating drum containing core materials (such as candies), onto which warm sucrose solution is ladled. The rotation distributes the syrup evenly as a thin coat on the cores and increases the surface area of the syrup that aids in evaporation of the water. As the water evaporates, the sugar hardens and coats the cores. For pharmaceutical products, perforated pans are used and the coating solution, usually an aqueous solution, is sprayed onto the tumbling cores.

Air-suspension coating- This technique is also popularly termed as Wurster coating or Fluidised Bed Coating. 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 (usually heated) flows inside the cylinder, causing the particles to rise rapidly. At the top, as the air stream diverges and slows, they settle back onto the outer bed and move downward to repeat the cycle. The process of movement through the inner cylinder repeats several times in few minutes (en.wikipedia.org/wiki/Micro-encapsulation). Several patents have been granted for this technique and a few among this has been enlisted in Table no. 2.

Table No. 2: Patents Granted For Air Suspension Microencapsulation Technique

Patent NO. and Date

Name of Method

Discussion

Reference

US/ Patent 6022525, (Feb 8 2000)

Preparation of diagnostic agents

Microcapsules are prepared by a process comprising the steps of (i) spray-drying a solution or dispersion of a wall-forming material in order to obtain intermediate microcapsules and (ii) reducing the water-solubility of at least the outside of the intermediate microcapsules. Suitable wall-forming materials include proteins such as albumin and gelatin. The microcapsules have walls of 40-500 nm thick and are useful in ultrasonic imaging. The control of median size, size distribution and degree of insolubilisation and cross-linking of the wall-forming material allows novel microsphere preparations to be produced.

(freepatentsonline.com /6022525.html)

US/ Patent 8192841 (June 5 2012)

Microencapsulated delivery vehicle having an aqueous core

Microencapsulated delivery vehicles comprising an active agent are disclosed. The microencapsulated delivery vehicles may be introduced into products such that, upon activation, the product provides a functional benefit to a substrate, such as a user's skin.

(freepatentsonline.com/ 8192841.html)

US/ Patent 4749575 (June 7 1988)

Microencapsulated medicament in sweet matrix

Any orally administrable medicament is prepared into a dosage form which eliminates the unpleasant taste and mouth feel of the medicament and is easily and pleasantly ingested even by children, by microencapsulating the medicament into microcapsules of less than 300 microns diameter, and embedding the microcapsules into a soft, sweet, palatable matrix, such as chocolate

(freepatentsonline.com/ 4749575.html)

US/ Patent 4925674 (May 15 1990)

Amoxicillin microencapsulated granules

The invention disclosed is amoxicillin microencapsulated granules with activity densities greater than about 0.200 g/ml. These granules are unusually small having diameters less than about 1000 microns. The granules optionally have a taste mask coating, and are particularlyuseful in hand-held flowable material dispensers. A process for manufacturing such granules is also disclosed.

(freepatentsonline.com/ 4925674.html)

Spray–drying- The process produce microcapsules approaching a spherical structure in the size range of 5 to 600 microns .Spray drying yield products of low bulk density owing to the porous nature of the coated particles (Leon Lachman et al,1991). This method is a single-step, closed-system process applicable to a variety of materials. The drug is dissolved or suspended in a suitable (either aqueous or non-aqueous) solvent containing polymer materials. The solution or suspension is atomized into a drying chamber, and microparticles form as the atomized droplets are dried by heated carrier gas (Swarbrick James, 2007).

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Recent Microencapsulation Techniques

Ionotropic Gelation
This technique involves cross-linking of poly electrolytes in the presence of multivalent counter ions. For example, spraying a sodium alginate solution into calcium chloride solution produces rigid gel particles. Technique is often followed by polyelectrolyte complexation with oppositely charged poly electrolytes. This complexation forms a membrane of polyelectrolyte complex on the surface of the gel particles, and this membrane increases the mechanical strength of the particles. For calcium alginate gel particles, polylysine is often used for this purpose. Now a days, it has widely been used for both cell and drug encapsulation (Swarbrick James, 2007).

Coacervation
This microencapsulation technique has been used for various consumer products. This method is based on separation of a solution of hydrophilic polymer(s) into two phases, which are small droplets of a dense polymer-rich phase and a dilute liquid phase. Coacervation may be brought about by various means. This process can be induced by-
1. A change in temperature of the system
2. A change in pH
3. A change in electrolyte balance
4. Addition of nonsolvents
5. Addition of other material which are incompatible with the polymer solution

On the base of number of polymers this technique can be divided into simple and complex coacervation.

1- Simple Coacervaiton- It involves only one polymer (e.g., cellulose, gelatin, polyvinyl alcohol, carboxymethyl), the phases separation can be induced by conditions that result in desolvation (or dehydration) of the polymer phase. These conditions include addition of a water-miscible non-solvent, such as acetone, isopropanol, ethanol, dioxane, or propanol, addition of inorganic salts, such as sodium sulfate, and temperature.

2- Complex coacervation- This type of coacervation involves two opposite charges hydrophilic polymers. Its involves polymer-polymer interaction. Eg. gelatin-gum arabic system.In the gelatin-gum Arabic system, pH should be below the isoelectric point of gelatin so that the gelatin can maintain the positive charge. Once embryonic coacervates form around the dispersed oil or solid phases, these polymer complexes are stabilized by cross-linking using glutaraldehyde (Swabrick james 2007) (Encyclopedia of controlled drug delivery, John Wiley $sons Inc.). Several patents have been granted for this technique and a few among this has been enlisted in Table no. 3.

Basically complex coacervation process consists of three steps:
[1] Formation of an oil-in-water emulsion
[2] Formation of the coating
[3] Stabilization of the coating

Figure No. 2:  Coacervation Technique (info@gate2tech.com)

Table No. 3: Patents Granted for Coacervation Microencapsulation Technique

Patent NO.

Name of Method

Discussion

Reference

US/ Patent 4808408 (Feb 28 1989)

Microcapsules prepared by coacervation

There is disclosed an improved complex coacervation process for microencapsulation of core ingredients that are partially soluble in the microcapsule walls wherein the core ingredient is first mixed with a coacervation adjacent prior to forming a first colloidal emulsion of core ingredient, and, after combining the first emulsion with a second colloidal solution and cooling to cause gelation, a water-soluble wax derivative is added. No pH adjustment or dilution is necessary, and very high yields of non-agglomerated microcapsules are obtained, both in terms of quantity of microcapsules and content of core ingredient. When deet (N,N-diethyl-m-toluamide) is the core ingredient there is obtained a long-lasting mosquito repellent

(freepatentsonline.com/ 4808408.html)

US/ Patent 5540927 (July 30 1996)

Microencapsulation process by coacervation

There is disclosed a process for microencapsulation of materials by means of complex coacervation employeing gelatin and polyaspartic acid. Material to be encapsulated is emulsified in an aqueous solution of gelatin. Polyaspartic acid or a salt thereof is employed to provide a counter ion to the gelatin which, when induced to precipitate from solution by cooling and/or pH change forms a wall around the material. The wall is hardened by crosslinking to form a stable microcapsule containing the material.

(freepatentsonline.com/ 5540927.html)

US/ Patent Application 20090253165 (OCT 08 2009)

Method for preparing microcapsules by coacervation

The present invention relates to a method for preparing microcapsules by coacervation, and to the use of transglutaminase for cross-linking in complex coacervation. The present invention relates further to coacervation processes in general in which a material to be encapsulated is added to a solution comprising at least one colloid below the gelling temperature of the colloid. According to a method of the present invention, an emulsion or suspension of hydrophobic material is prepared after cooling a solution that includes hydrocolloids below the critical gelling temperature of a coacervate phase.

(freepatentsonline.com/ y2009/0253165.html)

US/ Patent 3872024 (March 18 1975)

Encapsulation Process by Simple Coacervation Using Inorganic Polymers

A process is disclosed for liquid-liquid phase separation utilizing certain inorganic polymeric materials as phase-separation-inducing materials. The disclosed process is conducted in an aqueous liquid manufacturing vehicle and the material which emerges as a liquidphase is an aqueous solution comprising organic hydrophilic polymeric material. The liquid-liquid phase separation of this disclosure is of the type generally named "simple" coacervation wherein a major portion of the organic hydrophilic polymeric material is included in theseparated, emergent, liquid phase and the phase-separation-inducing material is substantially evenly distributed, as to concentration, between the separated phase and the manufacturing vehicle. Preferred materials for use in practicing the present invention include gelatin as the organic hydrophilic polymeric material and polysilicates and polyphosphates as the inorganic polymeric phase-separation-inducing materials. The liquid-liquid phase separation of the present invention is useful for, among other things, manufacturing, en masse, minute capsules having the organic and inorganic hydrophilic polymeric material as capsule wall material.

(freepatentsonline.com/ 3872024.html)

US/ Patent 3878121 (April 15 1975)

Method of encapsulation by coacervation, and the substances obtained

The present invention relates to a method of encapsulation by coacervation of fine particles of a very reactive substance such as an alkali metal or a very powerful reducing agent. The said substance is suspended in a polyurethane resin solution made up of constituents which do not react with the substance, the coacervate is obtained by adding more of one of the constituents of the solution, the resulting mixture is dispersed in a slightly polar liquid which does not mix with the mixture and contains in solution an agent for cross-linking polyurethane resin, and the encapsulated substance is then separated from the liquid and dried.

(freepatentsonline.com/ 3878121.html)

US/ Patent Application 20080089927 (April 17 2008)

Methods for Coacervation Induced Liposomal Encapsulation and Formulations Thereof

The present invention relates to methods of preparing liposomal formulations of active agents comprising varying the reaction parameters to form a coacervate which yields liposomal formulations of unusually high active agent (drug) to lipid ratios.

(freepatentsonline.com/ y2008/0089927.html)

US/ Patent 3639256 (Feb 1 1972)

Encapsulation Process by Complex Coacervation Using Inorganic Polymers

A process is disclosed for manufacturing capsules, en masse, by use of a liquid-liquid phase separation which includes certain inorganic material as complexing, phase-separation-inducing, polymer. The disclosed process is conducted in an aqueous capsule manufacturing vehicle and the material which emerges as a liquid phase is an aqueous solution of organic hydrophilic polymeric material and inorganic polymeric material complexed together. The liquid-liquid phase separation of this invention is the type generally named "complex"coacervation wherein the separated, emergent, liquid phase includes a major portion of both, the organic hydrophilic polymeric material and the phase-separation-inducing material; in this invention, inorganic polyacid polymeric material. The organic polymeric material and the inorganic polymeric material are complexed together by virtue of opposite electrical charges, the complex is at least partially immiscible with the manufacturing vehicle, and the manufacturing vehicle contains only a minor amount of either polymeric material. Preferred materials for use in practicing the present invention include gelatin as the organic hydrophilic polymeric material and polymolybdates and polytungstates as the inorganic polymeric phase-separation-inducing material.

(freepatentsonline.com/ 3639256.html)

US/ Patent Application 20090189304 (July 30 2009)

Encapsulation of oils by coacervation

The present invention describes the encapsulation of water insoluble oils by coacervation and the subsequent reduction in oxidative degradation of these oils in microencapsulated forms. Water insoluble oils useful in the process of the invention include food oils such as PUFA, flavor oils, and agriculturally and pharmaceutically active oils.

(freepatentsonline.com/ y2009/0189304.html)

US/ Patent Application 20070048385 (March 01 2007)

Microcapsules by coacervation containing a pharmaceutical incorporated in the coating polymer

Microcapsules containing an active ingredient, constituted by a core coated with a polymer membrane, characterized in that the active ingredient is incorporated in the polymer coating layer, and in that said layer is applied using microencapsulation techniques (coacervation by means of phase separation). The microcapsules; thus produced have excellent properties of taste masking and prolonged release of the active ingredients.

(freepatentsonline.com/ y2007/0048385.html)

US/ Patent Application 20090263480

Taste-Masked Pharmaceutical Compositions Prepared by Coacervation

There is provided a method for preparing an orally disintegrating tablet (ODT) composition comprising microparticles of one or more taste-masked active pharmaceutical ingredients, rapidly-dispersing microgranules, and other optional, pharmaceutically acceptable excipients wherein the ODT disintegrates rapidly with saliva in the buccal cavity forming a smooth, easy-to-swallow suspension. Furthermore, the microparticles (crystals, granules, beads or pellets containing one or more actives) with a taste-masking membrane applied by a modified solvent coacervation process comprising a water-insoluble polymer and at least one gastrosoluble inorganic or organic pore-former, exhibit a pleasant taste when placed in the oral cavity and provide rapid, substantially-complete release of the dose on entry into the stomach.

(freepatentsonline.com/ y2009/0263480.html)

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Polymerization
Polymerization technique forms protective microcapsule coating insitu.It involves the reaction of monomeric units located at the interface existing between a core material substance and a continuous phase in which the core material is dispersed. The continuous or core material supporting phase is usually a gas or liquid and therefore polymerization  reactions occurs at liquid-liquid, liquid-gas, solid-liquid, or liquid-solid interface (Leon lachman et al 1991). Polymerization can be classified in to three types:-

  • Interfacial polymerization
  • Matrix polymerization
  • Interfacial cross-linking
  • Insitu polymerization

Interfacial Polymerization- It involves the condensation of two monomers at the interface of the organic & aqueous phase. In the interfacial polymerization, the two reactants in a polycondensation meet at an interface and react rapidly. The basic of this method is the classical schotten-baumaan reaction between an acid chloride and a compound containing an active hydrogen atom, such as amine or alcohol, polyesters, polyurea, polyurethane. Under the right condition, thin flexible walls form rapidly at the interface. A solution of the pesticide and a diacid chloride are emulsified in the water and an aqueous solution containing an anime and a polyfunctional isocyanate is added. Bases are present to neutralize the acid formed during the reaction. Condensed polymer forms wall instantaneously at the interface of emulsion droplets. (Swabrick James, 2007) (Encyclopedia of controlled drug delivery, John Wiley $sons Inc.).

Figure No. 3: Polymerization

Interfacial cross-linking- A number of hydrophilic polymers from natural origin, such as gelatin, albumin, starch, dextran, hyaluronic acid, and chitosan, can be solidified by a chemical or thermal cross-linking process. Most proteins are cross-linked using glutaraldehyde, but its toxicity remains a problem for pharmaceutical applications.

In-situ polymerization- In this process, the direct polymerization of a single monomer is carried out on the particle surface. In one process, e.g. Cellulose fibers are encapsulated in polyethylene while immersed in dry toluene. Usual deposition rates are about 0.5μm/min. The coating is uniform, even over sharp projection. (en.wikipedia.org/wiki/Micro-encapsulation), (Swabrick James, 2007).

Matrix polymerization- a core material is imbedded in a polymeric matrix during formation of the particles. A simple method of this type is spray-drying, in which the particle is formed by evaporation of the solvent from the matrix material. However, the solidification of the matrix also can be caused by a chemical change.

Table No. 4: Patents Granted for Matrix polymerization Microencapsulation Technique

Patent NO.

Name of Method

Discussion

Reference

US/ Patent 4963364 (Oct 16 1990)

Microencapsulated antitumor agent

Thermally polymerized copolyamino acids are used to microencapsulate a chemotherapeutic compound for more efficient drug delivery.

(freepatentsonline.com/4963364.html)

US/ Patent 4948506 (Aug 14 1990)

Microencapsulated medicament in sweet matrix

Interfacially-polymerized ultrathin films containing physicochemically functional groups are disclosed, both with and without supports. Various applications are disclsoed, including membrane electrodes, selective membranes and sorbents, biocompatible materials, targeted drugdelivery, and narrow band optical absorbers.

(freepatentsonline.com/4948506.html)

US/ Patent 6080412 (June 27 200)

Pharmaceutical microencapsulation

A method of producing a microencapsulated pharmaceutical formulation is disclosed comprising causing a dye to be attached to the surfaceof pharmaceutical particles or particle clusters and applying a source of radiant energy to the dye in the presence of a liquid polymeric or polymerisable material so as to cause the material to cross-link, producing a conformal layer of cross-linked polymer on the particulate surfaces. Preferably, the polymer provides an immuno-protective layer around the particles, while allowing therapeutic components to exit the microcapsules. Microencapsulated pharmaceutical formulations and their medical use are also disclosed, especially for the treatment ofdiabetes by encapsulating insulin secreting cells.

(freepatentsonline.com/6080412.html)

EP/ 0342685 (April 13 1994)

Microencapsulating composition and kit; and process for producing microcapsules

An improved microencapsulating composition comprising an emulsifying agent and a compound that is capable of reacting with water to form a membrane but which is not reactive with said emulsifying agent is disclosed. Also disclosed are: a microencapsulating composition comprising said first microencapsulating composition and an active ingredient (e.g. agrichemical, flavor, paint, liquid crystal, repellent against pest and rodent, fertilizer, cosmetic, pigment, ink, attractant, foaming agent, flame retardant, corrosion inhibitor or mold inhibitor) to bemicroencapsulated; a process for producing microcapsules using either one of the two microencapsulating compositions; and a kit consisting of the first microencapsulating compositions and a component to be microencapsulated. By mixing the first microencapsulatingcomposition with both a component to be microencapsulated and a solvent such as water, or by simply mixing the secondmicroencapsulating composition with the solvent, microcapsules that are stable and that have good handling properties can be produced with ease.

(freepatentsonline.com/
EP0342685B1.html)

US/ Patent 4766012 (Aug 23 1988)

Microencapsulation of a medicament

The present invention relates to a process for the microencapsulation of a medicament by means of at least one coating agent, characterized in that is comprises the following steps:

(a) Dissolution of the coating agent in water, by salification;

(b) Dispersion of the particles of medicament to be microencapsulated, first in water, and then into the solution of the salified coating agent according to (a);

(c) Addition to the so-obtained suspension of an acidifying substance, which causes the precipitation of the coating agent onto the particles ofmedicament while these are being kept in suspension by stirring, thus microcapsules being formed.

(d) Recovery of microcapsules.

 (freepatentsonline.com/4766012.html)

US/ Patent 4518547 (May 21 1985)

Microencapsulation process

Nylon coated microcapsules containing hydrophilic solvent-soluble anionic, cationic or quaternary drug salts were prepared by interfacialpolycondensation techniques. In a first stage, the drug substance to be encapsulated is dissolved in an aqueous phase. Examples of drugsencapsulated are morphine sulfate, diphenhydramine hydrochloride, and methantheline bromide. Next the aqueous drug solution is dispersed in an organic phase. In a second stage complementary polycondensation reactants each in an organic phase are added separately, either sequentially or simultaneously, to the dispersion prepared in the first stage. Microcapsules of nylon form around the hydrophilic solvent soluble core drug substance.

(freepatentsonline.com/4518547.html)

Emulsion Solidification
Microparticles can be produced from emulsion of two or more immiscible liquids. solution of hydrophobic drug and polymer in an organic solvent (oil phase, dispersed phase) is emulsified in an aqueous solution containing an emulsifying agent (water phase, continuous phase) to produce oilin- water (o/w) emulsion. The drug containing polymer particles can be solidified as the solvent is removed. (Swabrick James, 2007).

Solvent evaporation
One of the oldest and most widely used methods of microcapsules preparation is the solvent evaporation technique. It is modification of phase precipitation. Technique is most widely used manufacturing technique for biodegradable microspheres. To facilitate solvent evaporation, the emulsion is often heated slightly above the boiling point of the solvent. For example, when methylene chloride (boiling point: 39.8oC) is used as an organic solvent, the emulsion is heated to 400C. The micro spheres formation process consists of three stages- Droplet formation, Droplet stabilization and Micro sphere stabilization. Drugs or diagnostic agents, either in soluble form or dispersed as fine solid particles, are added to the polymer solution, and then this mixture is emulsified in an aqueous solution that contains an emulsifying agent such as poly(vinyl alcohol) (PVA). The resulting emulsion is stirred until most of the organic solvent evaporates, leaving solid microparticles that may be washed with water and freeze-dried (Encyclopedia of controlled drug delivery, John Wiley $sons Inc.), (Swabrick james, 2007), (Leon lachman et al 1991).

Figure No. 4: Solvent Evaporation Method

Solvent extraction
non-volatile solvents can be removed by extraction into the continuous phase. This can be done by using a solvent that has significant solubility in the continuous phase, increasing the concentration difference between the dispersed and continuous phase, or adding a third solvent into the continuous phase to facilitate extraction of the solvent. This method depends on high vapor pressure of the solvent so this method requires volatile solvents such as methylene chloride.

Hot-Melt Microencapsulation
The polymer is first melted and then mixed with solid drug particles or liquid drugs. This mixture is suspended in an immiscible solvent and heated to 5o C above the melting point of the polymer under continuous stirring. The emulsion is then cooled below the melting point until the droplets solidify. “Hot melt” terminology because it consists of a re-crystallization of molten lipids around the nucleus leading to the protection of either liquid or solid phase material from its environment. Such shell is able to release under precise conditions* its content (*pH for enteric release for example).

Figure No. 5: Hot Melt Microencapsultion

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The technology to be applied will depend on the way the particles are considering before the encapsulation process. Two possibilities are there;
Individualization of the particles before encapsulation
Blending of the matrix and the substrate to be protected before separation (Tarun et al, 2011).

Solvent exchange method (A novel microencapsulation technique)
A solvent exchange method is employed to provide microencapsulated compositions, such as microcapsules of pharmaceutical preparations. The method is based on an exchange of water and a hydrophilic organic solvent, whereby a decline in solvent quality for the organic solvent causes a polymer dissolved therein to be deposited onto an aqueous core. Optimal results are rationalized in terms of a balance of water solubility and surface tension for the organic solvent. In a preferred embodiment, microcapsules of selected drugs are formed by contacting microdroplets of an aqueous solution containing the drug with the organic solvent containing a polymer dissolved therein(Yoon Yeo et al. 2003).

This technique could address traditional difficulties that have been encountered during the microencapsulation of protein drugs. Reservoir-type microcapsules were produced using a dual microdispenser system or a coaxial ultrasonic atomizer, based on midair collision between component materials followed by interfacial phase separation of a polymeric membrane. It was found that the reported process had no negative effect on functional integrity of the encapsulated model protein, lysozyme. Furthermore, the microcapsules released the encapsulated lysozyme at near zero-order for an extended period when tested without drying. The reported example demonstrated a complete release of intact lysozyme over 50 days. It is believed that these results are additive effects of following features of the new microencapsulation method. First, the method minimizes the exposure of encapsulated proteins to a large water/organic solvent interfacial area, in which the proteins can easily accumulate and be denatured. Second, the method utilizes only a minimal energy for producing microdrops and does not generate damagingly strong mechanical stresses. Third, the contact between the encapsulated drugs and the hydrophobic polymer and their degradation products is minimal in the reservoir-type microcapsules, which could otherwise cause extensive denaturation of the encapsulated proteins. The new method provides a simple and efficient way of making protein-loaded microcapsules, which will lead to commercially viable products in the near future. (Yoon Yeo 2003)

Table No. 4: Patents Granted for Solvent Exchange Microencapsulation Technique

Patent NO.

Name of Method

Discussion

Reference

US/ Patent 6599627 (July 29 2003)

Microencapsulation of drugs by solvent exchange

A solvent exchange method is employed to provide microencapsulated compositions, such as microcapsules of pharmaceutical preparations. The method is based on an exchange of water and a hydrophilic organic solvent, whereby a decline in solvent quality for the organic solvent causes a polymer dissolved therein to be deposited onto an aqueous core. Optimal results are rationalized in terms of a balance of water solubility and surface tension for the organic solvent. In a preferred embodiment, microcapsules of selected drugs are formed by contacting microdroplets of an aqueous solution containing the drug with the organic solvent containing a polymer dissolved therein. A preferred method employs biodegradable poly(lactic acid-co-glycolic acid) (PLGA) dissolved in acetic acid, ethyl acetate, methyl acetate, or ethyl formate, to form a PLGA membrane around an aqueous drug core. The method is particularly attractive for encapsulating protein-based drugs without substantial denaturation.

(freepatentsonline.com/ 6599627.html)

US/ Patent 7442439 (Oct 28 2010)

Microencapsulated heat delivery vehicles

Microencapsulated delivery vehicles comprising an active agent are disclosed. In one embodiment, the microencapsulated delivery vehicles are heat delivery vehicles capable of generating heat upon activation. The microencapsulated heat delivery vehicles may be introduced into wet wipes such that, upon activation, the wet wipe solution is warmed resulting in a warm sensation on a user's skin. Any number of other active ingredients, such as cooling agents and biocides, can also be incorporated into a microencapsulated delivery vehicle

(freepatentsonline.com/ 7442439.html)

US/ Patent 8192841 (June 05 2006)

Microencapsulated delivery vehicle having an aqueous core

Microencapsulated delivery vehicles comprising an active agent are disclosed. The microencapsulated delivery vehicles may be introduced into products such that, upon activation, the product provides a functional benefit to a substrate, such as a user's skin.

(freepatentsonline.com/ 8192841.html)

US/ Patent Application 20020160109 (Oct 31 2002)

Microencapsulation of drugs by solvent exchange

A solvent exchange method is employed to provide microencapsulated compositions, such as microcapsules of pharmaceutical preparations. The method is based on an exchange of water and a hydrophilic organic solvent, whereby a decline in solvent quality for the organic solvent causes a polymer dissolved therein to be deposited onto an aqueous core. Optimal results are rationalized in terms of a balance of water solubility and surface tension for the organic solvent. In a preferred embodiment, microcapsules of selected drugs are formed by contacting microdroplets of an aqueous solution containing the drug with the organic solvent containing a polymer dissolved therein. A preferred method employs biodegradable poly(lactic acid-co-glycolic acid) (PLGA) dissolved in acetic acid, ethyl acetate, methyl acetate, or ethyl formate, to form a PLGA membrane around an aqueous drug core. The method is particularly attractive for encapsulating protein-based drugs without substantial denaturation.

(freepatentsonline.com/y2002/0160109.html)

References
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2.Pachuau et al (2008) “Formulation and evaluation of matrix microspheres for simultaneous delivery of salbutamol sulphate and theophylline” Tropical Journal of Pharmaceutical Research, June 2008; 7 (2): P. No. 995-1002.
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