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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



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.


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.


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.


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.


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.


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.


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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