Chemistry Reference
In-Depth Information
TABLE 9 . 3 . Summary of Key Atomization Spray Drying Process Parameters
Parameter
Variable Type
Dened by
M
soln
Input/
independent
Evaporation capacity of dryer
Desired physical properties of SDD
Target atomization pressure
P
nozzle
Input/
independent
Equipment constraints
Target droplet size
Nozzle geometry (e.g., design,
swirl channel open area,
ori
Input/
independent
Nozzle manufacturer
Target droplet or SDD particle size
ce diameter)
Solids content
Input/
independent
Solubility limit of drug or polymer in
the spray solvent
Can be limited by viscosity of spray
solution (e.g., incomplete atomiza-
tion or buildup)
Target droplet or SDD particle size
Droplet size
Output/
dependent
Combination of all input variables
To expand upon the thermodynamic model output and begin to use quality-by-
design (QbD) principles, a product-speci
ned for the spray
drying process based on the thermodynamic constraints. An example follows.
The thermodynamic operating space for the spray drying process can be de
c operating space can be de
ned in a
rational manner by understanding the impact of the key spray drying process variables on
the process and SDD product. Although
T
out
is a dependent variable, it is known to have
the greatest impact on drying rate and thus residual solvent content and SDD morphol-
ogy. This is demonstrated by a typical response curve for an SDD formulation of bulk
speci
c volume (BSV) to
T
out
, as shown in Figure 9.9a. In addition, scanning electron
micrography (SEM) images (Figure 9.9b and c) for the extremes of the
T
out
range show
the change in particle morphology that is observed across this range (Figure 9.9d and e).
Lower
T
out
values result in higher SDD densities with a shriveled or buckled morphol-
ogy, whereas at higher
T
out
values, low-density in
ated spheres are observed [5,11].
Using relationships of the process space to the formulation attributes allows for
straightforward selection of initial design space for the SDD process. Four different
criteria are typically applied during this exercise.
1.
Maximum T
in
: Deposits of material near the gas disperser inlet to the drying
chamber may be exposed to temperatures near the
T
in
. Chemical and physical
stability or discoloration of the SDD should be evaluated to select a temperature
that will minimize these process risks. In addition, active cooling of the gas
disperser inlet can be implemented to reduce this risk (Niro DPH design).
2.
Process Ef
c drying ratio, is generally maximized within
the operating space to achieve throughput goals for the product.
ciency
:
M
soln
, or speci
