Chemistry Reference
In-Depth Information
spray-dried dispersion prior to secondary drying (hereinafter referred to as wet SDD)
were the response factors. A total of 148 runs were completed in the 13 factorial designs.
Another 14 runs were added from data attained during the production of the associated
designs, creating a
final data set of 162 runs. These large numbers of runs, when both API
and spray drying time were available, provided opportunities to learn and establish a
more thorough understanding of the spray drying process. This understanding will be
extremely helpful for development of future molecules.
Particle size spray drying model statistics [47] (regression model, parameter
estimates, and prediction pro
ler) are summarized in Figure 11.6a
-
d. The prediction
pro
ler plots indicate the relative magnitude of the effect of each process parameter. For
particle size, the significant process parameters are solids content of the spray drying
mixture, nozzle ori
ce diameter, feed pressure, outlet temperature, and spray dryer
equipment. Each of these parameters has a similar magnitude of effect on particle size in
the range investigated, except for spray dryer type that has a smaller effect: on average
the particle size shifts by 7
m comparing the PSD4 with the FSD12.5. Also shown is that
process variables can be adjusted when changing spray dryers to attain a similar particle
size. Equation 11.1 summarizes a particle size spray drying model. In the similar manner,
a bulk density spray drying model is generated.
μ
PS
wet
a
bP
feed
c
SD
Type
dT
out
e
TS
fD
Nozzle
gP
feed
SD
Type
hD
Nozzle
TS
(11.1)
where PS
wet
is the volume median diameter of wet SDD (
m),
P
feed
is the feed pressure
μ
(bar), SD
Type
is the spray dryer type (FSD12.5
=
1; PSD4
=
1),
T
out
is the outlet
temperature (
C), TS is the total solids content (%, w/w), and
D
Nozzle
is the nozzle
diameter (mm).
The spray drying design space for the CQAs of particle size and bulk density is de
°
ned
by the relationships between (i) wet particle size, wet bulk density, and spray drying
process parameters and (ii) the change in particle size and bulk density from wet SDD
(post-spray drying) to dry SDD (post-secondary drying) by a series of design equations.
The design equations are bounded by the control limits for particle size and bulk density.
Contours plots can be used to illustrate spray drying design space, although the
effect of only two process parameters on the CQAs of PS and BD can be shown in each
contour plot. The effects of outlet temperature and feed pressure on particle size and bulk
density are illustrated in Figure 11.7. The contours in Figure 11.7a show predicted
particle size as a function of feed pressure and
T
out
. The acceptable particle size range is
50
m, and all combinations of feed pressure and outlet temperature studied
produced particle size within acceptable limits, apart from a small region in the upper
right-hand quadrant represented by the dotted black line. For the CQA of particle size, the
acceptable range of feed pressure and outlet temperature is de
-
110
μ
ned approximately by the
rectangle that encompasses the knowledge space. Figure 11.7b shows the predicted bulk
density as a function of these parameters. The acceptable range of bulk density is
0.33
0.52 g/cm
3
, and the dotted black line de
nes the boundary of unacceptably low
bulk density, which constrains the acceptable region for outlet temperature and feed
pressure, as illustrated. The region in which both particle size and bulk density are within
-
