Chemistry Reference
In-Depth Information
9.2 PROCESS BACKGROUND AND PHYSICAL SITUATION
Spray drying offers the opportunity to produce amorphous dispersions with superior physical
stability using a well-established unit operation. During spray drying, the API is dissolved in a
spray solution that may include a dispersion polymer, a spray solvent, and other excipients.
The spray solvent is evaporated from the spray solution droplets within milliseconds [4
6].
This rapid drying from solution to solid limits themobility of the API in the dispersion polymer
and makes it possible to produce a wide range of physically stable amorphous dispersions.
A wide variety of polymers can be used in this process. Thermodynamic solubility
of the API in the dispersion polymer is not required because the API can be kinetically
trapped during spray drying [1]. Due to the rapid drying kinetics, it is often possible to
achieve higher drug loadings in SDDs than in dispersions produced using other
manufacturing methods (e.g., hot melt extrusion). It is also possible to use polymers
with high glass transition temperatures (
T
g
) that can produce amorphous dispersions with
superior physical stability.
Critical quality attributes (CQAs) for SDDs, such as particle size and density, can be tuned
by controlling the spray solution composition, droplet formation, and drying rates. Particle size
can be controlled by selection of atomizers and atomization parameters (e.g., nozzle geometry,
nozzle pressure, atomizing gas pressure, and solution concentration) to produce the target
droplet size. The density and morphology of SDDs, which are often important to downstream
tablet or capsule manufacture, are controlled by the droplet drying rate through adjustment of
the thermodynamic parameters (e.g., dryer outlet temperature (
T
out
)).
Thus, by controlling atomization and drying parameters, SDD particles can be
engineered to enable a wide range of downstream formulation options, including liquid
presentations (e.g., suspensions or sachets), immediate-release solid oral dosage forms
(e.g., tablets or capsules), andmodi
-
ed-release solid oral dosage forms (e.g., osmotic tablets).
Since droplet drying, or solidi
cation, occurs very quickly, SDD particle attributes are
de
ned within a key control volume around the exit of the atomizer, where the liquid droplets
are formed and initially come into contact with the drying gas [4]. Figure 9.1 shows the
physical situation and key control volume for a typical spray dryer. As the
gure shows, the
liquid feed is atomized into discrete droplets. Solvent immediately begins to evaporate from
the droplet surface upon contact with the drying gas, leading to an initial free evaporation
drying phase. Most SDDs are formulated with somewhat viscous (depending on the spray
solution concentration)
film-forming polymers, which will skin quickly (on the order of
10 ms) after the initial free evaporation stage [5]. After skin formation or viscous gelation of
the polymer, the droplet drying rate is limited by internal mass transfer due to the added
diffusional resistance provided by the solidi
ed skin of the droplet. During this phase, the
droplet drying rate is signi
cantly slower than the rate of free solvent evaporation. Modeling
and experimental results have shown that the solidi
ed droplet or SDD particle subsequently
experiences heating to temperatures equivalent to
T
out
. If the droplet experiences a
temperature near or above the solvent boiling point at this stage of drying, the vapor
pressure inside the particle will keep the particle in
ated, leading to a
final particle with a
“
hollow sphere
”
morphology. This morphology often results in low bulk density (e.g.,
0.2 g/cm
3
) with good compactability. If the droplet experiences a temperature signi
cantly
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