Microcapsules

Two types of microparticles are described microspheres, with a matrix structure in which the active ingredient is dispersed or dissolved, and microcapsules, which are polymeric vesicles with an aqueous or oily core containing the active ingredient. 

Microparticles prepared in the presence of CyDs are shown in Fig. 15.2. In microcapsules and microspheres CyDs can either constitute a raw material for the shell of the capsules or the matrix of the spheres, or form with the active ingredient an inclusion complex dissolved or dispersed in the shell or the matrix [9-34]. 

Only superficial complexation occurs as a result of this loading method, and the loading cannot be properly called encapsulation . The main disadvantage associated with this technique, is that the superficial loading leads to a fast release in aqueous medium. 

However, a true encapsulation within the capsule cavity seems possible by introducing the drug into the internal phase of the emulsion. That may be feasible for 

Microcapsules of synthetic polymer and cyclodextrin Three examples in the literature mention an association between synthetic polymer microcapsules and CyDs [12-14] as a means of encapsulating drugs complexed with CyDs. 

The required conditions for shell formation on inhibitor particles in these systems are  

Polyvinyl acetate Acetone Trichloroethylene Methanol Water Hexane Butyl or isoamyl alcohol 

Polyvinyl stearate Benzol Chlorophorm Kerosene Acetone Methyl ethyl ketone Mineral oil 

Polyvinyl chloride Nitrocellulose and cellulose acetates Cellulose acetobutyrate Cyclohexane Acetone Methyl ketone Glycol Water Isopropyl ether 

Ethyl cellulose Xylol Ethyl alcohol Benzol Hexane, heptane Water Mineral oil 

The resultant product of the microencapsulation process is termed a microcapsule . Such capsules are of micrometer size ( 1 pm), and have a spherical or ir- 

Core materials in microcapsules may exist in the form of either a solid, liquid or gas. The core materials are used most often in the form of a solution, dispersion or emulsion. Compatibility of the core material with the shell is an important criterion for enhancing the efficiency of microencapsulation, and pretreatment of the core material is very often carried out to improve such compatibility. The size of the core material also plays an important role for diffusion, permeability or controlled-release applications. Depending on applications, a wide variety of core materials can be encapsulated, including pigments, dyes, monomers, catalysts, curing agents, flame retardants, plasticizers and nanoparticles. 

The abundance of natural and man-made polymers provides a wider scope for the choice of shell material, which may be made permeable, semi-permeable or impermeable. Permeable shells are used for release applications, while semi-permeable capsules are usually impermeable to the core material but permeable to low molecular-weight liquids. Thus, these capsules can be used to absorb substances from the environment and to release them again when brought into another medium. The impermeable shell encloses the core material and protects it from the external environment Hence, to release the content of the core material the shell must be ruptured by outside pressure, melted, dried out dissolved in solvent or degraded under the influence of light (see Chapter 7). Release of the core material through the permeable shell is mainly controlled by the thickness of the shell wall and its pore size. The dimension of a microcapsule is an important criterion for industrial applications the following section will focus on spherical core-shell types of microcapsules (Fig. 1.8). 

Assuming that the density of the core (p ) and shell (p ) materials are identical (i.e., p = pg), it is possible to establish the relationship between the shell thickness (dj, = T r J and the ratio of the weight of the shell material (w ) to that of the core material (wj  

Equation (2) shows a linear relationship between the shell thickness and the capsule diameter when the ratio of wJ(Wg+w,) is in the range of 0.50 to 0.95 [83]. 

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Microencapsulation is the coating of small solid particles, liquid droplets, or gas bubbles with a thin film of coating or shell material. In this article, the term microcapsule is used to describe particles with diameters between 1 and 1000 p.m. Particles smaller than 1 p.m are called nanoparticles particles greater than 1000 p.m can be called microgranules or macrocapsules. 

Many terms have been used to describe the contents of a microcapsule active agent, actives, core material, fill, internal phase (IP), nucleus, and payload. Many terms have also been used to describe the material from which the capsule is formed carrier, coating, membrane, shell, or wall. In this article the material being encapsulated is called the core material the material from which the capsule is formed is called the shell material. 

Table 1 Hsts representative examples of capsule shell materials used to produce commercial microcapsules along with preferred appHcations. The gelatin—gum arabic complex coacervate treated with glutaraldehyde is specified as nonedible for the intended appHcation, ie, carbonless copy paper, but it has been approved for limited consumption as a shell material for the encapsulation of selected food flavors. Shell material costs vary greatly. The cheapest acceptable shell materials capable of providing desired performance are favored, however, defining the optimal shell material for a given appHcation is not an easy task.

Table 1. Shell Materials Used to Produce Commercially Significant Microcapsules...

Microcapsules can have a wide range of geometries and stmctures. Figure 1 illustrates three possible capsule stmctures. Parameters used to characteri2e microcapsules include particle size, size distribution, geometry, actives content, storage stabiHty, and core material release rate. 

Fig. 1. Schematic diagrams of several possible capsule stmctures (a) continuous core/sheU microcapsule in which a single continuous sheU surrounds a continuous region of core material (b) multinuclear microcapsule in which a number of small domains of core material are distributed uniformly throughout a matrix of sheU material and (c) continuous core capsule with two different sheUs.

Classification of the many different encapsulation processes is usehil. Previous schemes employing the categories chemical or physical are unsatisfactory because many so-called chemical processes involve exclusively physical phenomena, whereas so-called physical processes can utilize chemical phenomena. An alternative approach is to classify all encapsulation processes as either Type A or Type B processes. Type A processes are defined as those in which capsule formation occurs entirely in a Hquid-filled stirred tank or tubular reactor. Emulsion and dispersion stabiUty play a key role in determining the success of such processes. Type B processes are processes in which capsule formation occurs because a coating is sprayed or deposited in some manner onto the surface of a Hquid or soHd core material dispersed in a gas phase or vacuum. This category also includes processes in which Hquid droplets containing core material are sprayed into a gas phase and subsequentiy solidified to produce microcapsules. Emulsion and dispersion stabilization can play a key role in the success of Type B processes also. 

Most Type A processes might be classified as chemical processes, whereas most Type B processes are classified as mechanical processes. Representative examples of both types of processes foUow. Type B processes tend to be promoted by organizations that seU and service equipment for producing microcapsules. Most Type A processes are not promoted by equipment manufacturers, but are developed and used by organizations that produce microcapsules. 

Complex Coacervation. This process occurs ia aqueous media and is used primarily to encapsulate water-iminiscible Hquids or water-iasoluble soHds (7). In the complex coacervation of gelatin with gum arabic (Eig. 2), a water-iasoluble core material is dispersed to a desired drop size ia a warm gelatin solution. After gum arabic and water are added to this emulsion, pH of the aqueous phase is typically adjusted to pH 4.0—4.5. This causes a Hquid complex coacervate of gelatin, gum arabic, and water to form. When the coacervate adsorbs on the surface of the core material, a Hquid complex coacervate film surrounds the dispersed core material thereby forming embryo microcapsules. The system is cooled, often below 10°C, ia order to gel the Hquid coacervate sheU. Glutaraldehyde is added and allowed to chemically cross-link the capsule sheU. After treatment with glutaraldehyde, the capsules are either coated onto a substrate or dried to a free-flow powder. 

Any pair of oppositely charged polyelectrolytes capable of forming a Hquid complex coacervate can be used to form microcapsules by complex... 

Interfacial Polymerization. Many types of polymerization reactions can be made to occur at interfaces or produce polymers that concentrate at interfaces thereby producing microcapsules. Accordingly, this approach to encapsulation has steadily developed into a versatile family of encapsulation processes. Figure 4 schematically illustrates five types of encapsulation processes that utilize these types of reactions. 

Fig. 4. Schematic diagrams that illustrate the different types of interfacial polymerization reactions used to form microcapsules. Reactants X, Y polymerization product (X — Y)—n or —(X—See text for descriptions of cases (a)—(e).

A key feature of encapsulation processes (Figs. 4a and 5) is that the reagents for the interfacial polymerisation reaction responsible for shell formation are present in two mutually immiscible Hquids. They must diffuse to the interface in order to react. Once reaction is initiated, the capsule shell that forms becomes a barrier to diffusion and ultimately begins to limit the rate of the interfacial polymerisation reaction. This, in turn, influences morphology and uniformity of thickness of the capsule shell. Kinetic analyses of the process have been pubHshed (12). A drawback to the technology for some apphcations is that aggressive or highly reactive molecules must be dissolved in the core material in order to produce microcapsules. Such molecules can react with sensitive core materials. 

Spray Drying. Spray-dry encapsulation processes (Fig. 7) consist of spraying an intimate mixture of core and shell material into a heated chamber where rapid desolvation occurs to thereby produce microcapsules (24,25). The first step in such processes is to form a concentrated solution of the carrier or shell material in the solvent from which spray drying is to be done. Any water- or solvent-soluble film-forming shell material can, in principle, be used. Water-soluble polymers such as gum arable, modified starch, and hydrolyzed gelatin are used most often. Solutions of these shell materials at 50 wt % soHds have sufficiently low viscosities that they stiU can be atomized without difficulty. It is not unusual to blend gum arable and modified starch with maltodextrins, sucrose, or sorbitol. 

Microcapsules are used in a number of pharmaceutical, graphic arts, food, agrochemical, cosmetic, and adhesive products. Other specialty products also exist, thus the concept of microencapsulation has been accepted by a wide range of industries. In order to illustrate how microcapsules are used commercially, it is appropriate to describe a number of commercial microcapsule-based products and the role that microcapsules play in these products. 

Fig. 10. Cross section of a three-part business form prepared from carbonless copy paper where are microcapsules and ...

Microencapsulation has much hidden potential for the food industry which promises to be tapped in the future (62). An interesting discussion of the problems that have been encountered while attempting to develop microcapsule formulations for commercial use in food products has been presented (65) and a review provides a number of references to food encapsulation studies (66). 

Microcapsules are used in several film coatings other than carbonless paper. Encapsulated Hquid crystal formulations coated on polyester film are used to produce a variety of display products including thermometers. Polyester film coated with capsules loaded with leuco dyes analogous to those used in carbonless copy paper is used as a means of measuring line and force pressures (79). Encapsulated deodorants that release their core contents as a function of moisture developed because of sweating represent another commercial appHcation. Microcapsules are incorporated in several cosmetic creams, powders, and cleansing products (80). 

A majority of the fasteners used in automobiles in the United States are coated with microcapsules loaded with an adhesive. When the fastener is installed, a fraction of the capsules in the coating mpture releasing the adhesive payload. The adhesive essentially glues the fasteners in place preventing them from becoming loose and causing rattles. The capsules are designed so that only a fraction of them break each time a fastener is taken off and put back. The on/off cycle can be repeated three or four times. 

New Developments. Creation of microencapsulation technology and appHcations of microcapsules are goals that many research and... 

C. Thies, How-to-Make Microcapsules Eecture and Eab Manual, Thies Technology, St. Louis, Mo., 1994. 

Carbonless Copy Paper. In carbonless copy paper, also referred to as pressure-sensitive record sheet, an acid-sensitive dye precursor, such as crystal violet lactone or /V-hen2oy11eucomethy1ene blue, is microencapsulated with a high boiling solvent or oil within a cross-linked gelatin (76,83,84) or in synthetic mononuclear microcapsules. Microcapsules that have a starch binder are coated onto the back of the top sheet. This is referred to as a coated-back (CB) sheet. The sheet intended to receive the image is treated on the front (coated-front (CF)) with an acid. When the top sheet is mechanically impacted, the dye capsules mpture and the dye solution is transferred to the receiving sheet where the acid developer activates the dye. 

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