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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).

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



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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