Microencapsulation is one of the few areas that truly bridge the physical and biomedical sciences. Microspheres are spherical solid matrices ranging in size from 1 to 1,000 microns, and may be made of a wide range of materials including glass, inorganic oxides, metals and various natural and synthetic polymers. In the pharmaceutical arena, microspheres have been intensively studied for use as drug delivery systems, where they have been shown to protect sensitive macromolecules from enzymatic degradation, and allow controlled release and tissue targeting of the formulated drug. Drug delivery using microparticles is one of the most important drivers of the rapidly changing pharmaceutical industry, with a >80 % increase in the number of microencapsulation technology patents in the last 5 years. Commercialised microsphere formulations include Embosphere™ (for embolisation), Aristin™ (Minocycline hydrochloride), Lupron Depot™ (Leuprolide Acetate) Yttrium 90-SIR™ (Yttrium-90 for Beta radiation in cancer therapy) and Promaxx™ (Insulin treatment for diabetes), with many more expected in the near future. The anticipated arrival of new bioactive macromolecules (such as enzymes, vaccine antigens, hormones and genetic material) in this era of rapid biotechnological advancement suggest that this upward trend is far from abating.

The subject of drug microencapsulation using biodegradable polymers has been intensively studied. One of the most suitable methods involves the formation of a multiple-phase system where the organic polymer phase is dispersed into a non-miscible aqueous continuous phase (usually by homogenisation) and the solvent of the polymer phase removed by extraction into the continuous phase. Alternatively the drug/polymer mixture as a single or binary phase mixture may be spray-dried to produce a dry powder of the polymer microspheres. The stability of the multiple-phase mixtures, and the removal of the solvent at the liquid/liquid interface are crucial when using these methods.

Under microgravity conditions the normal dynamic coalescence/droplet rupture is eliminated; there is no fluid flow over the surface of the droplet, hence mass transfer processes are diffusion controlled with no convection and no vibration. Thus, under these conditions the formation of microspheres during the initial stages may be studied, and the physico-chemical factors controlling the structure and morphology established.

It has also been shown that fluid instability at the interface during formation of the microspheres plays an important role in determining the performance of the microspheres as carriers of therapeutics (Crotts and Park ). When immiscible phases are in contact and molecular transport occurs between the phases, it has long been known that fluid instability can develop and lead to interfacial turbulence (Sternling and Scriven ). The mechanism by which the turbulence is produced is thought to involve convection, both surface tension-driven (or Marangoni) convection, and buoyancy-driven convection. In order to have surface tension-driven convection, there must be a gradient in surface tension along the interface between two-phases. Such a gradient can be produced by variations in either the phase (or solvent) concentration, or temperature. During solvent extraction, molecular transport between phases is a necessary part of the procedure, and is therefore vulnerable to fluid instability. The presence of Marangoni-induced instabilities can be amplified by buoyancy-driven convection. The presence of buoyancy-driven convection is almost eliminated under conditions of microgravity, providing an ideal environment in which to study the role of these complex fluid transport mechanisms, when only a single one is present at a time.

The molecular arrangement of the drug and polymer is also of significance to the formulated final product. The release kinetics of the drug molecule, and the interaction of the microspheres with cells in vivo had been shown to be influenced by the crystallinity of the polymer. Microgravity conditions are conducive to larger crystal formation, and may also affect the orientation and location of the encapsulant within the microsphere matrix. The significance of this is more pronounced for microencapsulated vaccine formulations.

Microgravity-based experiments will establish the fundamental mechanisms behind the solvent transport processes involved in microencapsulation, and will contribute to our understanding and ultimate control of the important parameters. The results may be used to enhance microsphere fabrication, and the ultimate benefit of this knowledge and technology will be realised in the health and biotechnology industries.

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