Encapsulation capsule

The encapsulation of preservatives is another interesting area for research. Procedures for encapsulation, capsule properties, and capsule size are important factors to be determined. Slow release fungicides by means of hydrolyzable linkages is also an interesting possibility. 

Keywords Self-assembly Hydrogen-bonding Host-guest Encapsulation Capsule... 

FIGURE 11.2 Photograph (a) and TEM image (h) of CN-encapsulated capsules prepared by dispersion nanoobjects protective encapsulation (DOPE). Reprinted with permission from Ref. [17]. 

Dronabinol. Marinol ( ii7R-/n7 j )-6i7,7,8,I0i7-tetrahydro-6,6,9-trimethyl-3-pentyl-6JT-diben2o(B,D) pyran-I-ol is the principal psychoactive substance present in Cannabis sativa F., ie, marijuana. It is a controlled substance, formulated in sesame oil and encapsulated in soft gelatin capsules for oral adrninistration. 

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.

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. 

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. 

Polymer—polymer iacompatibiHty encapsulation processes can be carried out ia aqueous or nonaqueous media, but thus far have primarily been carried out ia organic media. Core materials encapsulated tend to be polar soHds with a finite degree of water solubiHty. EthylceUulose historically has been the sheU material used. Biodegradable sheU materials such as poly(D,L-lactide) and lactide—glycoHde copolymers have received much attention. In these latter cases, the object has been to produce biodegradable capsules that carry proteias or polypeptides. Such capsules tend to be below 100 p.m ia diameter and are for oral or parenteral administration (9). 

Figure 4a represents interfacial polymerisation encapsulation processes in which shell formation occurs at the core material—continuous phase interface due to reactants in each phase diffusing and rapidly reacting there to produce a capsule shell (10,11). The continuous phase normally contains a dispersing agent in order to faciUtate formation of the dispersion. The dispersed core phase encapsulated can be water, or a water-immiscible solvent. The reactant(s) and coreactant(s) in such processes generally are various multihmctional acid chlorides, isocyanates, amines, and alcohols. For water-immiscible core materials, a multihmctional acid chloride, isocyanate or a combination of these reactants, is dissolved in the core and a multihmctional amine(s) or alcohol(s) is dissolved in the aqueous phase used to disperse the core material. For water or water-miscible core materials, the multihmctional amine(s) or alcohol(s) is dissolved in the core and a multihmctional acid chloride(s) or isocyanate(s) is dissolved in the continuous phase. Both cases have been used to produce capsules. 

Figure 5 illustrates the type of encapsulation process shown in Figure 4a when the core material is a water-immiscible Hquid. Reactant X, a multihmctional acid chloride, isocyanate, or combination of these reactants, is dissolved in the core material. The resulting mixture is emulsified in an aqueous phase that contains an emulsifier such as partially hydroly2ed poly(vinyl alcohol) or a lignosulfonate. Reactant Y, a multihmctional amine or combination of amines such as ethylenediamine, hexamethylenediamine, or triethylenetetramine, is added to the aqueous phase thereby initiating interfacial polymerisation and formation of a capsule shell. If reactant X is an acid chloride, base is added to the aqueous phase in order to act as an acid scavenger. 

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. 

Figure 4c illustrates interfacial polymerisation encapsulation processes in which the reactant(s) that polymerise to form the capsule shell is transported exclusively from the continuous phase of the system to the dispersed phase—continuous phase interface where polymerisation occurs and a capsule shell is produced. This type of encapsulation process has been carried out at Hquid—Hquid and soHd—Hquid interfaces. An example of the Hquid—Hquid case is the spontaneous polymerisation reaction of cyanoacrylate monomers at the water—solvent interface formed by dispersing water in a continuous solvent phase (14). The poly(alkyl cyanoacrylate) produced by this spontaneous reaction encapsulates the dispersed water droplets. An example of the soHd—Hquid process is where a core material is dispersed in aqueous media that contains a water-immiscible surfactant along with a controUed amount of surfactant. A water-immiscible monomer that polymerises by free-radical polymerisation is added to the system and free-radical polymerisation localised at the core material—aqueous phase interface is initiated thereby generating a capsule sheU (15). 

Figure 4c also describes the spontaneous polymerisation ofpara- s.yX en.e diradicals on the surface of soHd particles dispersed in a gas phase that contains this reactive monomer (16) (see XylylenePOLYMERS). The poly -xylylene) polymer produced forms a continuous capsule sheU that is highly impermeable to transport of many penetrants including water. This is an expensive encapsulation process, but it has produced capsules with impressive barrier properties. This process is a Type B encapsulation process, but is included here for the sake of completeness. 

Figure 4d represents in situ encapsulation processes (17,18), an example of which is presented in more detail in Figure 6 (18). The first step is to disperse a water-immiscible Hquid or soHd core material in an aqueous phase that contains urea, melamine, water-soluble urea—formaldehyde condensate, or water-soluble urea—melamine condensate. In many cases, the aqueous phase also contains a system modifier that enhances deposition of the aminoplast capsule sheU (18). This is an anionic polymer or copolymer (Fig. 6). SheU formation occurs once formaldehyde is added and the aqueous phase acidified, eg, pH 2—4.5. The system is heated for several hours at 40—60°C.

A unique feature of in situ encapsulation technology is that polymerization occurs ia the aqueous phase thereby produciag a condensation product that deposits on the surface of the dispersed core material where polymerization continues. This ultimately produces a water-iasoluble, highly cross-linked polymer capsule shell. The polymerization chemistry occurs entirely on the aqueous phase side of the iaterface, so reactive agents do not have to be dissolved ia the core material. The process has been commercialized and produces a range of commercial capsules. 

Several parenteral microencapsulated products have been commercialized the cote materials ate polypeptides with hormonal activity. Poly(lactide— glycohde) copolymers ate the sheU materials used. The capsules ate produced by solvent evaporation, polymer-polymer phase separation, or spray-dry encapsulation processes. They release their cote material over a 30 day period in vivo, although not at a constant rate. 

Another biomedical appHcation of mictocapsules is the encapsulation of Hve mammalian ceUs for transplantation into humans. The purpose of encapsulation is to protect the transplanted ceUs or organisms from rejection by the host. The capsule sheU must prevent entrance of harmful agents into the capsule, aUow free transport of nutrients necessary for ceU functioning into the capsule, and aUow desirable ceUular products to freely escape from the capsule. This type of encapsulation has been carried out with a number of different types of Hve ceUs, but studies with encapsulated pancreatic islets or islets of Langerhans ate most common. The alginate—poly(L-lysine) encapsulation process originally developed in 1981 (54) catalyzed much of the ceU encapsulation work carried out since. A discussion of the obstacles to the appHcation of microencapsulation in islet transplantation reviewed much of the mote recent work done in this area (55). Animal ceU encapsulation has also been researched (56). 

Encapsulated dia2innon sold as Knox-Out 2FM is a commercial encapsulated pesticide formulation said to have reduced dermal and oral toxicity as well as prolonged effectiveness. The capsules, prepared by interfacial polymeri2ation, are claimed to be highly effective against cockroaches with no objectionable odor and low insect repeUence. The capsules are beheved to function as a contact poison when insects walk on it and as a stomach poison when insects preen capsules stuck to their legs and ingest them (71). 

The encapsulation of herbicides has received much attention. Encapsulated alachlor is a high volume herbicide product generally sold as a Hquid formulation, although a dry granule version is also available. The capsules, produced by interfacial polymeri2ation (11), are reported to be spherical with a diameter of 2—15 p.m (75). Two thiocarbamate herbicides, EPTC and vemolate [1929-77-7], were encapsulated by interfacial polymeri2ation because they are volatile compounds. When appHed in unencapsulated form, they must be incorporated in the soil within two hours in order to provide effective weed control. When appHed as a microencapsulated formulation, the rate of volatili2ation is lower and soil incorporation can be delayed 24 hours (76). 

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). 

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