Chemistry Reference
In-Depth Information
Assessment of API solubility in solvent systems is critical. Solvents typically used
during the spray drying process are limited by precedence and fall within the FDA
Class 2 or 3 classi
cation [10]. The most commonly used solvents in the spray drying
process include acetone, methanol, THF, and DCM, although many others can be used.
Ideally, a single solvent can be found to provide adequate solubility of the drug,
polymer, and excipients. However, it is also common to usemixed solvent systems to further
enhance drug solubility or providemutual solubility of the drug and excipients.Water is also
commonly added to mixed solvent systems (typically less than 30wt% of total solvent) due
to its miscibility with a wide range of solvents and its ability to increase the solubility of the
API or the excipients. The solubility and physical state of functional excipients also should
be evaluated carefully tomaximize formulation and process robustness. For example, use of
cosolvents that allow for complete dissolution of a polymer versus a colloidal solution may
be critical for achieving the desired physical state of the SDD.
Additional consideration is given to the overall volatility of the spray solvent. Key
properties related to volatility are the latent heat of vaporization and the boiling point.
Volatility de
nes the overall throughput of the spray drying process and impacts the
cycle time of the secondary drying process.
9.4.2 Process Variables
An overview of process parameter de
nition is shown in Table 9.2 and Figure 9.6 and
discussed in detail throughout this section. A rationale strategy (discussed previously) [4]
can be used to streamline this approach during the development stage.
The key process variables that are critical to under-
standing the spray drying process are summarized in Table 9.2. Each variable is
important to the attributes of the SDD and has a speci
9.4.2.1 Thermodynamics
c relationship or input into
the overall process de
ne each process parameter
based on a known relationship to the SDD and eliminate the need for empirical
approaches to process de
nition. The goal is to rationally de
nition.
The thermodynamic operating space of the spray drying process can be defined by
conducting a mass and energy balance for the process using the drying chamber as a
TABLE 9 . 2 . Summary of Key Thermodynamic Spray Drying Process Parameters
Parameter
Variable Type
De
ned by
T
in
Input/independent
Formulation physical or chemical stability
constraints
M
gas
Input/independent
Scale of equipment
M
soln
Input/independent
Target evaporation rate of spray dryer
T
cond
Input/independent
Equipment constraints at large scale, drying rate
of product
T
out
Output/dependent on inputs
Desired particle attributes, physical stability
RS
out
Output/dependent on inputs
Desired particle attributes, product recovery
constraints
