Biomedical Engineering Reference
In-Depth Information
7.4.4.2
Particles from Preformed Polymers
7.4.4.2.1 Solvent Evaporation
Solvent evaporation is perhaps the easiest and the most extensively used method of microencap-
sulation. An organic phase consisting of the polymer solution in solvents such as dichloromethane
(or ethyl acetate or chloroform) is mixed with the drug to form the primary water-in-oil emulsion.
This emulsion is then added to a large volume of water containing an emulsifi er like PVA or PVP
to form the multiple emulsions (w/o/w). The so-formed double emulsion is then subjected to stirring
until most of the organic solvent evaporates, leaving solid microspheres. The microspheres can then
be washed, centrifuged, and lyophilized to obtain the free-fl owing and dried microspheres.
There are numerous examples of particles that can be prepared using this technique. PLA and
the copolymer of lactic and glycolic acid (PLGA) are the most frequently used particles because
of their high biocompatibility. Numerous studies were undertaken to utilize PLGA matrix for oral
protein delivery [141].
7.4.4.2.2 Spray Drying
In this process, the drug may be dissolved or dispersed in the polymer solution and spray dried. The
quality of spray-dried microspheres can be improved by the addition of plasticizers, for example,
citric acid, which promote polymer coalescence on the drug particles and hence promote the
formation of spherical and smooth-surfaced microspheres. The size of microspheres can be con-
trolled by the rate of spraying, the feed rate of polymer drug solution, nozzle size, and the drying
temperature. This method of microencapsulation is particularly less dependent on the solubility
characteristics of the drug and polymer and is simple, reproducible, and easy to scale up.
7.4.4.2.3 Hot Melt Microencapsulation
This method was adopted to prepare polyanhydride copolymer of poly(bis( p -carboxy phenoxy) pro-
pane anhydride) with sebacic acid [132]. In this method, the polymer is fi rst melted and then mixed
with solid particles of the drug. The mixture is suspended in a nonmiscible solvent (e.g., silicone oil),
continuously stirred, and heated to 5°C above the melting point of the polymer. Once the emulsion
is stabilized, it is cooled until the polymer particles solidify. The resulting microspheres are washed
by decantation with petroleum ether. The primary objective for developing this method is to develop
a microencapsulation process suitable for the water-labile polymers, for example, polyanhydrides.
Microsphere with diameter of 1-1000 μm can be obtained, and the size distribution can be easily
controlled by altering the stirring rate.
7.4.4.2.4 Complex Coacervation
When oppositely charged polyelectrolytes with a relatively low-charge density are mixed at an
appropriate temperature and pH concentration, a liquid polyelectrolyte complex called complex
coacervate is formed. This technique is widely used in the preparation of polymeric particles.
Sodium alginate is a water-soluble polymer that gels in the presence of multivalent cations such
as calcium, zinc, and barium. Alginate particles are usually produced by dropwise extrusion of
sodium alginate solution into calcium chloride solution. The preparation of alginate nanoparticles
was fi rst achieved in a diluted aqueous sodium alginate solution in which gelation was induced by
the addition of a low concentration of calcium. Alginate particles can be prepared by using a modi-
fi ed emulsifi cation or internal gelation. The preparation of alginate nanoparticles by this method
does not require specialized equipment and can be performed at an ambient temperature.
Numerous processes are reported for the preparation of chitosan-based particulate system, and
excellent review articles have appeared for the same recently. Emulsion cross-linking, coacerva-
tion precipitation, spray drying, emulsion droplet coalescence, reverse micellar method, sieving
method, ionic gelation process, etc., are widely used in the fabrication of chitosan-based nano- and
microparticles. Ionic gelation process has generated much attention since the process involved is
simple and mild. Moreover reversible physical cross-linking by ionic interaction between anionic
 
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