Preparation Of Microcapsules By Temperature Change Method

Table 8.12 Depot forms employing polymeric films and matrices"

Type

Materials'3

Diagrammatic representation Mechanisms

1 Barrier coating

2 Fat embedment

3 Plastic matrix

4 Repeat action

5 Ion exchange

Beeswax, glyceryl monostearate, ethylcellulose, nylon (Ultramid IC), acrylic resins (Eudragit retard)

Glycerol palmitostearate (Precirol), beeswax, glycowax, castorwax, aluminium monostearate, carnauba wax, glyceryl monostearate, stearyl alcohol

Polyethylene Poly(vinyl acetate) Polymethacrylate Poly(vinyl chloride) Ethylcellulose

Cellulose acetylphthalate

Amberlite Dowex

6 Hydrophilic matrix Carboxymethylcellulose

Sodium carboxymethylcellulose Hydroxypropylmethylcellulose

7 Epoxy resin beads Epoxy resins

8 Microcapsules Polyamides, gelatin

9 Soft gelatin depot Shellac-PEG

capsules Poly(vinyl acetate)-PEG

drug coating drug

drug polym enteric coat hydrophilic polymer drug epoxy resin bead or microcapsule

Diffusion

Erosion, hydrolysis of fat, dissolution

Leaching, diffusion

Dissolution of enteric coat

Dissociation of drug-resin complex

Gelation, diffusion

Dissolution of resin or swelling, diffusion

Diffusion a Modified from W. A. Ritschel, in Drug Design, vol. IV (ed. A. J. Ariens), Academic Press, New York, 1974.

b Materials are not all polymeric. The waxes are included for completeness; these depend on conferring a hydrophobic layer on the drug, tablet or granule to prevent access of solvent.

8.6.3 Microcapsules and microspheres

Microencapsulation is a technique which, as its name suggests, involves the encapsulation of small particles of drug, or solution of drug, in a polymer film or coat. Microspheres, on the other hand, are solid but not necessarily homogenous particles which can entrap drug. Although the terms tend to be used interchangeably, we retain the distinction here. Microspheres can be prepared also by a variety of techniques which are briefly discussed in the section on nanoencapsulation below.

Typical photomicrographs of poly(e-caprolac-tone) microphores are shown in Fig. 8.30.

Microcapsules can be prepared by three main processes:

• Coacervation of macromolecules around the core material, this being induced by temperature change, solvent change or addition of a second macromolecule of appropriate physical properties.

• Interfacial polymerisation of a monomer around the core material by polymerisation at the interface of a liquid dispersion.

• Spray coating and other methods in which larger particles may be coated in suspension.

Any method which will cause a coherent barrier to deposit itself on the surface of a liquid droplet or a solid particle of drug may be applied to the formation of microcapsules. Many so-called microencapsulation procedures result in the formation of macroscopic 'beads' which are simply coated granules.

Coacervation

Coacervation is the term used to describe the separation of macromolecular solutions into colloid-poor and colloid-rich (coacervate) phases when the macromolecules are desol-vated. The liquid or solid to be encapsulated is dispersed in a solution of a macromolecule (such as gelatin, gum arabic, carboxymethyl-cellulose or poly(vinyl alcohol)) in which it is immiscible. A nonsolvent, miscible with the continuous phase but a poor solvent for the polymer, under certain conditions will induce the polymer to form a coacervate (polymer-rich) layer around the disperse phase. This coating layer may then be treated to give a rigid coat of capsule wall. This is the process of simple coacervation. Successful application of the technique relies on the determination of the appropriate conditions for coacervate deposition, which can be achieved not only by the addition of nonsolvents such as ethanol and isopropanol and salts (sodium and ammonium sulfates) but also by the choice of macromolecules incompatible under selected conditions with the first species. The latter process is termed complex coacervation. In both simple and complex coacervation utilising hydrophilic macromolecules it is the decrease in solubility which results in deposition of the macromolecule layer at the particle-solution interface.

Desolvation of water-insoluble macro-molecules in nonaqueous solvents leads to the deposition of a coacervate layer around aqueous or solid disperse droplets. Table 8.13 lists both water-soluble and water-soluble macromolecules which have been used in coacervation processes. Desolvation, and thus coacervation, can be induced thermally and

Table 8.13 Materials used in coacervation micro

encapsulation

Water-soluble

Water-insoluble

macromolecules

macromolecules

Arabinogalactan

Cellulose acetate phthalate

Carboxymethylcellulose

Cellulose nitrate

Gelatin

Ethylcellulose

Gum arabic (acacia)

Polyethylene vinyl acetate)

Hydroxyethylcellulose

Poly(methyl methacrylate)

Poly(acrylic acid)

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