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(Bülau and Ulrich, 1997; Bashiri-Shahroodi et al., 2008). When the melt is pipetted
directly into a gelatine capsule, the process is called “direct capsule filling” (Francois and
Jones, 1978).
2.1.2 Solvent methods
Solvent methods for the manufacturing of solid dispersions require that both the drug and
the carrier dissolve into the same solvent system, which may contain one or more solvents.
The solvent can then be evaporated by various means; the simplest is by leaving the vessel
open or by using, for example, rotary evaporator (Betageri and Makarla, 1995). More
sophisticated methods are presented in the next paragraphs.
Spray-drying
Evaporation of the solvents in the spray dryer occurs as atomized droplets of the solution
are fed into a heated gas flow (Cal and Sollohub, 2010). The process can be optimized by
adjusting the temperature and flow of the solution and the gas. In spray-drying the
material dries fast, which supports the formation of the amorphous product. Spray-drying
has been successfully utilized in the production of various solid dispersions (Yonemochi
et al., 1999; Takeuchi et al., 2005; Shen et al., 2009; Sollohub and Cal, 2010).
Freeze-drying
Freeze-drying, also known as lyophilization, is a method where the solution is first
freezed, e.g. in liquid nitrogen, and the frozen solvents are then removed via sublimation
in a reduced pressure (Rowe, 1960; Tang and Pikal, 2004). As the process includes many
stages, it is usually slower than spray-drying. The lyophilized material had the most
advantageous dissolution properties when compared to solid dispersions produced by melt
method and solvent method utilizing rotavapor (Betageri and Makarla, 1995).
Supercritical fluid method
One option for producing solid dispersions without organic solvents or extreme
temperatures is supercritical fluid processing. The supercritical fluid can be used as a
solvent or as an antisolvent in order to produce solid dispersions; the processes slightly
vary depending on the approach taken. They may include also melting or dissolving the
drug in an organic solvent (Karanth et al., 2006). Carbon dioxide has many beneficial
properties, such as being nontoxic, non-flammable, and inexpensive. All these combined
with reasonable critical temperature and pressure makes carbon dioxide the most
commonly used supercritical fluid in the pharmaceutical field (Sethia and Squillante,
2002; Karanth et al., 2006). Various solid dispersion formulations have been prepared via
supercritical fluid processing (Sethia and Squillante, 2002; Gong et al., 2005; Miura et al.,
2010). As an example, in vivo evaluation of the supercritical fluid formulation surpassed
the solid dispersion prepared by the traditional solvent evaporation method (Miura et al.,
2010).
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