Chemistry Reference
In-Depth Information
below the solvent boiling point after skinning, the particle will maintain its surface area, but
collapse to a
“
shriveled raisin
”
morphology. This morphology often results in higher bulk
0.4 g/cm
3
) and lower compactability than the hollow spheres dried at higher
temperatures. The
density (e.g., 0.2
-
particles represent two extremes on
the particle morphology continuum that result from the spray drying process. As discussed in
this chapter, SDD bulk densities and morphologies can generally be correlated to and
modi
“
hollow sphere
”
and
“
shriveled raisin
”
ed by controlling
T
out
, relative solvent saturation (RS), or other process parameters.
Figure 9.1 shows the temperature contour output from a computational
fluid dynamics
(CFD) model of a typical nozzle-based spray drying process. As the
gure shows, the
evaporation plume is the coolest area in the drying chamber and the rest of the drying chamber
is at a temperature approximately equal to
T
out
. The result is mild temperature exposure,
which is especially important for compounds or formulations that may be thermally labile.
9.3 SPRAY DRYING EQUIPMENT
The spray drying process can be broken down into the following
five key steps or focus
areas, which are described below:
1.
Spray Solution Preparation
: Solid components are dissolved into a mutual
solvent.
2.
Atomization
: The solution is passed through a nozzle, creating discrete droplets
with a high surface area for rapid heat and mass transfer.
3.
Drying
: Atomized droplets are contacted with heated drying gas to remove
solvent and produce a dried particle.
4.
Product Collection
: A cyclone separator is used to remove the solids from the
drying gas.
5.
Secondary Drying
: A secondary drying process is used to remove residual
solvent from the SDD to a target residual solvent level.
An overview of these key areas for a spray drying equipment train to support SDD
manufacture is shown in Figure 9.2.
9.3.1 Spray Solution Preparation
The spray solution is prepared by dissolving the API with the dispersion polymer and
other desired excipients in an organic solvent system that provides mutual solubility of
each component. Solvents typically used include acetone, methanol, tetrahydrofuran
(THF), and dichloromethane (DCM). In addition, binary blends of these solvents or
solvent systems containing small fractions of water (e.g., 1
30% by mass) can be
advantageous for maximizing solubility of the API and polymer.
Spray solution tanks are sized based on the throughput and desired batch size of
the SDD at a given spray drying scale. Total solids concentration is de
-
ned by either the
maximum solubility of the API or the maximum spray solution viscosity that can be
atomized while maintaining target particle properties. Typically, API concentration is
limited by the equilibrium solubility of the API in the spray solution over process-
