Drying Technology

ISSN: 0737-3937 (Print) 1532-2300 (Online) Journal homepage: https://www.tandfonline.com/loi/ldrt20

Mathematical Modelling of the Primary and

Secondary Drying Stages of Bulk Solution Freeze-
Drying in Trays: Parameter Estimation and Model
Discrimination by Comparison of Theoretical
Results With Experimental Data

H. Sadikoglu & A. I. Liapis

To cite this article: H. Sadikoglu & A. I. Liapis (1997) Mathematical Modelling of the Primary
and Secondary Drying Stages of Bulk Solution Freeze-Drying in Trays: Parameter Estimation
and Model Discrimination by Comparison of Theoretical Results With Experimental Data,
Drying Technology, 15:3-4, 791-810, DOI: 10.1080/07373939708917262

To link to this article: https://doi.org/10.1080/07373939708917262

Published online: 07 May 2007.

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DRYING TECHNOLOGY.15(3&4). 791-810 (1997)

MATHEMATICAL MODELLING O F THE PRIMARY

AND SECONDARY DRYING STAGES O F BULK SOLUTION
FREEZE-DRYING IN TRAYS: PARAMETER ESTIMATION
AND MODEL DISCRIMINATION BY COMPARISON O F
THEORETICAL RESULTS WITH EXPERIMENTAL DATA

H. Sadikoglu and A. I. Liapis'

Department of Chemical Engineering and
Biochemical Processing Institute
University of Missouri-Rolla
Rolla, Missouri 65409-1230
U.S.A.

Kev Words: Freeze-drying of pharmaceuticals; lyophilization of

pharmaceuticals.

ABSTRACT

A mathematical model was constlucted and solved in order to describe

quantitatively the dynamic behavior of the primary and secondary drying stages of
the freeze-drying of pharmaceuticals in trays. The theoretical results were
compared with the experimental data of the freeze-drying of skim milk, and the
agreement between the experimental data and the theoretical results is good.
Detailed model calculations have indicated that the contribution of the removal of
hound (unfrozen) water to the total mass flux of the water removed during
primary drying, is not significant. For this reason, it was found that one could not

'Author to whom correspondence should be addressed.

791

CopyrighlO 1997 by Marcel Dekkcr. Inc.

792 SADIKOGLU AND LlAPlS

use effectively the experimental data of the primary drying stage to perform
studies on parameter estimation and model discrimination for determining the
functional form of the mechanism that could be used to describe the removal of
bound water. The constitutive equation and the values of the parameters of the
mechanism that could describe, for a given material of interest, the removal of
bound water, should be determined by using the experimental data of the
secondary drying stage. The results of this work indicate that one could neglect
the mechanism of the removal of bound water in the mathematical model during
primary drying, without introducing a significant error in the theoretical
predictions. Two different mechanisms for the removal of hound water were
examined, and it was found that a tirstdrder rate desorption mechanism could
describe the dynamic behavior of the removal of bound water satisfactorily. The
model presented in this work has a very important practical advantage when
compared with other models, because its expressions do not require detailed
information about the structure of the porous matrix of the dried layer of the
material being freeze-dried.

Many pharmaceutical products when they are in solution deactivate over a

period of time. Such pharmaceuticals can preserve their bioactivity by being
lyophilized soon after their production, so that the molecules are stabilized [1-4].
In the primary drying stage. the frozen solvent is removed by sublimation. As the
solvent (ice) sublimes, the sublimation interface, which started at the outside
surface (Figure I), recedes, and a porous shell of dried material remains. The
vaporized solvent (water) vapor is transported through the porous layer of dried
material. During the primary drying stage, some of the sorbed water (unfrozen
water) in the dried layer may be desorbed [I-51. The time at which there is no
more frozen layer (i.e., there is no more sublimation interface) is taken to
represent the end of the primary drying stage. The secondary drying stage
involves the removal of solvent (water) that did not freeze (this is termed sorbed
or bound water) [I-51. The secondary drying stage starts at the end of the primary
drying stage, and the desorbed vapor is transported through the pores of the
material being dried.
In this work, a mathematical model is presented and solved that employs
the mass transfer mechanisms of the dusty-gas model [5-8) to describe the
transport of the solvent (water) vapor and inert gas in the pores of the dried layer.
The very important practical advantage of the dusty-gas model is that it does not
require detailed information about the structure of the porous matrix of the
BULK SOLUTION FREEZE-DRYING IN TRAYS 793

dried layer, and thus, the structural parameters C,,, C,, and C, that characterize the
mechanisms of intraparticle convective flow (convective flow of a gas in the pores
of the dried layer), Knudsen diffusion, and bulk diffusion, respectively, could be
obtained from the analysis of the data of independent experiments [8] of moderate
complexity. Furthermore, two different rate mechanisms for the removal of
bound (unfrozen) water are examined in this work. The theoretical results of this
work are compared with the experimental freeze drying data of skim milk.

2. MATHEMATICAL MODEL

This work considers bulk solution freeze-drying in trays [1.2.5.9] and in

Figure I a material being freeze-dried in a tray is shown. The thickness of the
sides and bottom of the tray, as well as the material from which the tray is made,
are most often in practice such that the resistance of the tray to heat transfer could
be considered to be negligible [1,2,5,9]. Heat q, could be supplied to the surface
of the dried layer by conduction, convection, or radiation from the gas phase; this
heat is then transferred by conduction to the frozen layer. Heat q,, is supplied by a
heating plate and is conducted through the bottom of the tray and through the
frozen material to reach the sublimation interface or plane. The magnitude of the
amount of heat q, in the vertical sides of the tray is much smaller [1,2.5.9] than
that of q, or q,; q, represents the amount of heat transferred between the
environment in the drying chamber and the vertical sides of the tray. Because the
contribution of q, is rather negligible when compared to the contribution of q, and
q,, the contribution of q, to the drying rate will not be further considered
[1,2,5,9]. The terms N, and N, in Figure I represent the mass flux of water vapor
and the total mass flux, respectively, in the dried layer. The total mass flux is
equal to the sum of the mass fluxes of water vapor and inert gas. N, = N, + N,.
where N,,denotes the mass flux of the inen gas.
In the following sections, the mathematical models that are used in this
work to describe the dynamic behavior of the primary and secondary drying stages
of the freeze drying process, are presented.

In the primary drying stage sublimation occurs as a result of heat being

conducted to the sublimation interface through the dried (I) and frozen (0layers
 SADIKOGLU AND LlAPlS

x= 0
FREEZE-DRIED LAYER I I

x=x

\ \ FROZEN MATERIAL U
x=L

FIGURE 1; Diagram of a material on a tray during freeze-drying (the variable X

denotes the position of the sublimation interface (front) between the freezedried
layer (layer I)and the frozen material (layer IT)).

[1.2.51. Following the assumptions reponed in the work of Liapis and Bruttini [I]
and Millman et a]. [51, the energy balances in the dried (0 and frozen (U) layers
and the material balances in the dried layer (I),are as follows:

The term JC&t in Equations (I) and (3) accounts for the change in the
concentration of sorbed or bound water with time. Different rate mechanisms
have been considered [1.2.5,9] lo describe the change in the concenuation of
BULK SOLUTION FREEZE-DRYING IN TRAYS 795

bound water with time. Two different rate mechanisms are considered in this
work and their expressions are as follows:

In Equation (Sa), the variablec,; represents the weight fraction of sorbed water
in the solid which would be in local equilibrium with the partial pressure of water
vapor, p,. The study presented in this work uses skim milk as the model material.
and the functional form of C.; used in the calculations was constructed from the
procedure reported in the work of Aguilera and Flink [17]. The parameter k, in
Equation (5a) represents the solid film mass transfer coefficient thal characterizes
the linear driving force (C,; -C,,) of the rate mechanism for the removal of
bound water. In Equation (5b). the parameter k, represents the desorption rate
constant of the linear rate mechanism that could be used to describe the desorption
(removal) of bound water.
The dusty-gas model equations [S-81 were used to develop the following
expressions for the mass fluxes N, and Ni,:

N. = - - k- ap, + -
+ k,pi" - api"
I"
RTI[3a~ [ a ax))

The contribution of thermal mass diffusion to the mass fluxes, is insignificant by

comparison of the contributions of the mass transfer mechanisms [I-5. 101
796 SADlKOGLU AND LlAPlS

included in Equations (6) and (7). This has led us to exclude the mechanism of
thermal mass diffusion from the expressions of the model presented in this work.
The expressions for N, and N, given by Equations (6) and (7), respectively, are
inserted in Equations (3) and (4). while the expression for N, (N,=N,+N,) in
equation (I) is obtained from the sum of the expressions given by the right-hand-
side of Equations (6) and (7).
In the dried layer, effective parameters are considered which include the
physical properties of both the gas and solid, which have been considered to be
independent of space. The initial and boundary conditions of Equations (1)-(4)
and (5a) or (5b) are as follows:

T,=Tn=T,=To at t=0, O s x s L (8)

C,, = C& at t=O , OsxsL (10)

and,

for radiation heat transfer to the upper dried surface,

BULK SOLUTION FREEZE-DRYING IN TRAYS

For radiation only,

q, = OF(G
-(T,(I,L)Y) , t>o

For a thin film between the frozen material and lower plate,

The value of the film thermal conductivity, k,, could be estimated from the
expressions in [9.1 I], and suitably adjusted [9] to account for the lowered
pressure in the freeze-drying process.

The variable p, is the chamber water vapor pressure, usually determined by the
condenser design and assumed constant within the drying chamber. The variable
Po denotes the total pressure (Po=p,. + pi,) at x = 0, and is usually considered to
be approximately equal to the total pressure in the drying chamber.
The mathematical model is completely specified by a material balance at
the interface (x = X) which defines the velocity of the interface, V, as

The initial condition for Equation (21) is as follows:

X = O at t = O
798 SADIKOGLU AND LIAPIS

Equations ( I ) - (22) represent the mathematical model that was used, in

this work, to describe the dynamic behavior of the primary drying stage, and this
model involves a moving boundary which is represented by the time varying
position of the sublimation interface (X=X(t)). External transpon resistances can
be easily incorporated into this model by including the expressions developed by
Liapis and Litchfield [12]. However, in a well-designed freeze-dryer [1,2], the
external mass and heat transfer resistances are not significant [I-5,9,10]. The
equations of the model presented above were solved by using the numerical
method developed by Liapis and Litchfield 1131, and Millman 1141.
Two limits may possibly be reached during the primary drying stage.
First, the surface temperature. T,(t,O), must not become loo high because of the
risk of thermal damage; the value of T,(t.O) must be kept below the scorch
temperalum [1,2] of the material being dried. Second, the temperature of the
interface. T,, and the temperature T,(t,L) (the temperature at x=L) must be kept
below the melting point [1.2] of the frozen material being dried. The end of the
primary drying stage occurs when the position of the moving sublimation
interface is at X=L; this condition implies that at the end of the primary drying
stage there is no frozen (Q layer, and therefore, there is no moving sublimation
interface.

2.2 Seeondarv Dwine Staee

ln the secondary drying stage, there is no frozen ([I)layer, and thus, there
is no moving sublimation interface. The secondary drying stage involves the
removal of bound (unfrozen) water. The thickness of the dried layer is L, and the
energy balance in this layer is is follows:

The initial and boundary conditions of equation (23) are

T , = y ( x ) at I=[,., , OsxhL
BULK SOLUTION FREEZE-DRYING IN TRAYS 799

for radiation heat transfer to the upper dried surface,

The continuity equations for water vapor and inen gas are given by
Equations (3) and (4). while the equation for the removal of bound water is given
either by expression (5a) or (5b). The initial and boundary conditions for the
material balance equations of the secondary drying stage, are given by the
following expressions:

pin = O(x) at t=tX=, , OsxsL (29)

C, = v(x) at i=tx=, , OsxsL (30)

The functions y(x), 6(x), O(x) and v(x) provide the profiles of T,, p,, p, and C, at
the end of the primary drying stage or at the beginning of the secondary drying
stage; these profiles are obtained by the solution of the model equations for the
primary drying stage. It should be noted at this point that during the secondary
800 SADIKOGLU AND LlAPlS

drying stage. the temperature everywhere in the sample (OsxsL) should be kept
below the scorch temperature [l.2] of the material being dried.
The model equations for the secondary drying stage were solved by the
method of orthogonal collocation [13.15.16]. External transport resistances can
be easily incorporated into the model equations by including the expressions
developed by Liapis and Litchfield [12]. But, as was discussed in the previous
section (for the model equations of the primary drying stage), in a welldesigned
freeze-dryer [ 1.21 the external resistances should not be controlling in determining
the drying rate

3. RESULTS AND DISCUSSION

Skim milk is considered in the freeze-drying study of this work and was
selected because it could be considered as a complex pharmaceutical product in
the sense that it contains enzymes and proteins. The pilot plant freeze-dryer and
the experimental procedure used for the freeze-drying experiments, are presented
in the work of Liapis and Bmttini [I]. The theoretical results for the freeze-drying
of skim milk were obtained by solving simultaneously Equations (I)+) and (21)
for the primary drying stage, and Equations (3)-(5) and (23) for the secondary
drying stage. The values of the parameters as well as the expressions employed in
the evaluation of certain parameters of the theoretical model, are presented in
Table I. The values of the parameters were estimated from data obtained from
independent experimens [1.2.4.8.9.17] and by matching numerous sets of the
experimental freeze-drying data with the predictions of the theoretical model. The
melting. T,, and scorch. T,,,, temperatures of skim milk were -10•‹Cand 60•‹C,
respectively [I].
In Figures 2 and 3 the experimental data and the theoretical results for the
amount of water removed at various drying times during the primary drying stage.
are presented, for the cases when (i) the removal of bound water during the
primary drying stage is considered, as shown in Figure 2, and (ii) the removal of
bound water is not considered during the primary drying stage, as indicated in
Figure 3 where k, = k, = 0. The agreement between the experimental and
theoretical data in Figures 2 and 3 is, for all practical purposes, good, when one
considers the complexity of the freeze-drying process during the primary drying
stage. By comparing the results in Figure 2 when Equation (5a) is used to
describe the mechanism of the removal of bound water (k, = 6 . 6 1 10.'~")
~ and
when expression (5b) is employed for the desorption of bound water (k,=
BULK SOLUTION FREEZE-DRYING IN TRAYS 801

TABLE 1: Parameter values and expressions

Parameters Values and Ex~ressions

C,,, m' 7.219~10"'
Cl, m 3.85583x104
c
2 0.921
C, kJkg-K 1.6166
Cp,, kJkg*K 2.59
C,,, kJkg.K 1.93
C kg waterkg solid 0.6415
C kg waterkg solid exp (2.3[1.36-0.036(T-'P)])1100
D,,?, kg.m/sl 0.000143931(~~(1/~.+1/~,.))~'
k,, kW1m2.K 1.5358xIO"P
k,, kW1m.K 1 . 4 1 2 ~ 1 0 ~ ( ~ , + ~ , ) + 2 .lo4
165~
k,, kW1m.K (0.48819~,)+0.4685xlO"
L, m 0.02
p:, Nlm2 4.00
ph. N/m2 4.00
p:, Nlm2 1.07
p,. Nlm2 1.07
Po. N/m2 5.07
TO, K 233.15
Tm K 313.15
Tw. K 313.15
f(Tx), N/m2 133.3224[exp(-2445.5646mx+8.2312lloglO(Tx)-
0.01677006~~+1.20514xl0~'~~-6.757169)~
A , kJkg 2840.0
AH, i d k g 2687.4
E 0.785
P kg/m.s 18.4858[~~'~1(~~+650)]
PI.. kg/m3 215.0
PI. kg/ml 212.21
Po* kg/m3 1030.0
o. kWlm2.K' 5.676~10'"
802 SADIKOGLU AND LlAPlS

0.8
PRIMARY DRYING STAGE
m
x o EXPERIMENTAL DATA
- THEORETICAL RESULTS WITH k;68lxlO.' s'
@ 0.8 - THEORETICAL RESULTS WITH 1 6 = 6 . 4 8 ~ 1 ~ ' 9 . '

0 2 4 6 8 10 12

TIME, hours

FIGURE 2: Amount of water removed versus time during the primary drying
stage of the freeze-drying of skim milk. In this case, the theoretical model
accounts for the removal of bound water during primary drying

0.8

x
OI 0 EXPERIMENT
d
0.6
0
5LL
0.4

58
gb- 0.2
0
I
4

00
0 2 4 6 8 10 12

TIME. hours

FIGURE 3: Amount of water removed versus time during the primary drying
stage of the freeze-drying of skim milk. In this case, the theoretical model does
not account for the removal of bound water during primary drying.
BULK SOLUTION FREEZE-DRYING IN TRAYS 803

6.48~10-'s-'),it becomes apparent that the difference between the theoretical

results is quantitatively not significant, and furthermore. the value of k, is only
about 1.97% smaller than the value of k,, although k, and k, characterize different
functional forms (mechanisms) for the removal of bound water. Even when an
expression given by Equation (34)

is considered for the desorption rate constant, k,, the theoretical results obtained
using the expression given by Equation (5b) are, for all practical purposes, similar
to those obtained when k, is constant and equal to 6 . 4 8 ~10-'s-'. The results in
Figure 3 indicate that when the removal of bound water is not considered during
the primary drying stage, the agreement between the experimental and theoretical
results is, for all practical purposes, as good as when the removal of bound water
during the primary drying stage is considered (Figure 2). A comparison of the
results in Figures 2 and 3 indicates that the contribution of the removal of bound
water to the total mass flux of water removed during the primary drying stage, is
not significant, and for this reason one could not use effectively the experimental
data of the primary drying stage to perform studies on parameter estimation and
model discrimination for determining the functional form of the mechanism that
could be used to describe the removal of bound water. Furthermore, the results in
Figures 2 and 3 indicate that if the removal of bound water during the primary
drying stage is not considered and the term aCJat in Equations (I). (3). and (5a)
or (5b) is set equal to zero, the predictions of the mathematical model with dCJ&
= 0 would, for all practical purposes, agree with the experimental data as
satisfactorily as when the term dCJ& is considered to be non-zero in Equations
(1). (3). and (5a) or (5b).
In Figures 4 and 5 the experimental data and the theoretical results for the
amount of water remaining in the sample at various drying times during the
secondary drying stage, are shown, for the cases when (a) the mechanisms of mass
transfer of water vapor and inert gas in the pores of the dried layer consider
Knudsen diffusion, bulk diffusion, and convective flow (Q,= 7.219x10~"m2), as
shown in Figure 4, and (b) the mechanisms of mass transfer of water vapor and
inert gas in the pores of the dried layer account for Knudsen and bulk diffusion
but not for convective flow (C,, = O), as indicated in Figure 5. It should be noted
again at this point that during the secondary drying stage, the water vapor in the
804 SADIKOGLU AND LlAPlS

0.14
SECONDARY DRYING STAGE
0 EXPERIMENTAL OATA
THEORETICAL RESULTS WlTH k,=8.2110.' 9.'
\ THEORETICAL RESULTSWTH ~6=78xl0'1.'

\ IN THIS CASE. THE VALUE OF THE

PARAMETER C,. IS EQUAL TO 7 2 1 ~ x 1 0 . "m'

0.00 I 1
12 14 18 18 20 22
TIME. hours

FIGURE 4: Amount of r e s i d u a l w a t e r venus time during the s e c o n d a r y drying

stage of the freeze-drying of s k i m milk. In t h i s case, the c o n t r i b u t i o n of
convective flow in t h e p o n s of the d r i e d l a y e r i s c o n s i d e r e d

SECONDARY DRYING STAGE

EXPERIMENTALOATA
- THEORETICAL RESULTS WlTH ~ 8 . 2 ~ 1 i
0"
THEORETICAL RESULTS WlTH k=7.8rl0' a.
IN THIS CASE. THE VALUE OF THE
PARAMETER Co, IS EQUAL TO ZERO

0.00 I
12 14 18 18 20
TIME, hours

FIGURE 5: Amount of r e s i d u a l w a t e r v e n u s lime during the s e c o n d a r y drying

s t a g e of the freeze-drying of s k i m milk. In t h i s case, the contribution of
convective flow in the p o r e s of t h e dried l a y e r i s not c o n s i d e r e d .
BULK SOLUTION FREEZE-DRYING IN TRAYS 805

pores of the dried layer is formed from the removal of bound (unfrozen) water
from the phase of the solute (skim milk). Therefore, the contribution of the
removal of bound water to the total mass flux of water removed during the
secondary drying stage is dominant, and thus, the term aCJat in Equations (I).
(3). and (5a) or (5b) cannot be zero through the duration of the secondary drying
stage, and this implies that neither k, nor k, can be equal to zero during the
secondary drying stage. The agreement between the experimental and theoretical
data in Figures 4 and 5 is. for all practical purposes, good. The values of k, and k,
in Figures 4 and 5 that provide a good fit between experiment and theory, are
more than two orders of magnitude larger than the values of k, and k, obtained
during the primary drying stage (Figure 2). and this clearly indicates the
importance of the mass transfer mechanism of the removal of bound water during
the secondary drying stage. By comparing the results in Figure 4 when Equation
(5a) is used to describe the mechanism of the removal of bound water and when
expression (5b) is employed for the desorption of bound water, it becomes
apparent that the difference between the theoretical results is quantitatively not
significant, and furthermore, the value of k, is only about 4.88% smaller than the
value of k,, although k, and k, characterize different mechanisms for the removal
of bound water. The results in Figure 4 suggest that, for the freeze-drying system
studied in this work, there is insignificant difference in the predictions of the
theoretical model when Equation (5a) or (5b) is used for the mechanism of the
removal of bound water. I•’ one, for a given material of interest, could describe
satisfactorily the removal of bound water during the secondary drying stage by
using the mechanism described by Equation (5b), then one would not have to
construct an expression for the equilibrium variable C,,: it should be noted here
that the construction of an expression for c,; requires tedious and time
consuming adsorptionldesorption equilibrium experiments [1,2,4,5]. The results
in Figure 4 suggest that one, for a given material of interest, could use, as a first
approximation, the expression given by Equation (5b) to describe the removal of
bound water; the parameter k, could be considered to have a constant value or
could be given by the expression in Equation (34). A comparison of the results in
Figures 4 and 5 indicates that the effect of neglecting the convective flow (C,, = 0
for the theoretical results in Figure 5) of water vapor and inter gas in the pores of
the dried layer through the duration of the secondary drying stage, is not
significant in determing the dynamic behavior of the drying process during
secondary drying. This result suggests that, for the system studied in this work,
the three major mass transfer mechanisms during secondary drying were as
806 SADIKOGLU AND LIAPlS

follows: (I) removal of bound water from the phase of the solute. (2) Knudsen
diffusion, and (3) bulk diffusion. In general, it is recommended that the
mechanism of convective flow should be included in the inathematical model
used to describe the dynamic behavior of the secondary drying stage, since one,
for a given system of interest, cannot accurately estimate a priori the effect of the
contribution of the convective flow on the drying rate during secondary drying; if,
of course, numerous comparisons of theoretical results with experimental data
from the system of interest indicate that the contribution of the mechanism of
convective flow in the pores of the dried material is not significant during
secondary drying, then one could neglect the mechanism of convective flow in the
mathematical model used to describe the dynamic behavior of the secondary
drying stage.

4. CONCLUSIONS AND REMARKS

A mathematical model was constructed and solved in order to describe

quantitatively the dynamic behavior of the primary and secondary drying stages of
the freeze-drying of pharmaceuticals in trays. The theoretical results were
compared with the experimental data of the freeze-drying of skim milk, and it was
found that the agreement between the experimental data and the results obtained
from the theoretical model is, for all practical purposes, good. The model
presented in this work employs the mass transfer mechanisms of the dusty-gas
model [5-81 to describe the transport of the water vapor and inert gas in the pores
of the dried layer, and thus, this model has a very important practical advantage
when compared with other models reported in the literature since the expressions
of the dusty-gas model do not require detailed [ I 4 1 information about the
structure of the porous matrix of the dried layer. Two different mechanisms for
the removal of bound water were examined, and it was found that the first-order
rate desorption mechanism given in equation (5b) could describe the dynamic
behavior of the removal of bound water, for the freeze-drying system studied in
this work, sksfactorily. Funhermore, detailed model calculations performed in
this work have indicated that the contribution of the removal of bound water to
the total mass flux of the water removed during primary drying, is not significant;
therefore, one could neglect the mechanism of the removal of bound water in the
mathematical model during primary drying, without introducing a significant error
in the theoretical results obtained from the solution of the model.
BULK SOLUTION FREEZE-DRYING IN TRAYS 807

ACKNOWLEDGMENT

We are pleased to acknowledge helpful discussions with Dr. R. Bruttini of

Criofarma-Freeze Drying Equipment. Turin, Italy.

NOTATION

C, weight fraction of bound water in dried layer

C, heat capacity
C,, constant dependent only upon stmctlire of porous medium and giving
relative D'Arcy flow permeability
C, constant dependent only upon structure of porous medium and giving
relative Knudsen flow permeability
C, constant dependent only upon structure of porous medium and giving the
ratio of bulk diffusivity within the porous medium to the free gas bulk
diffusivity, dimensionless
,
.
D free gas mutual diffusivity in a binary mixture of water vapor and inen gas
D,; D d
Ed activation energy (Equation (34))
f a ) water vapor pressure-temperature functional form presented in Table I
thermal conductivity
bulk diffusivity constant =C~D&KJ(C,D;, +L P )
self diffusivity constant = (K,KJ(Cp& + KmP)) + (COilpm)
bulk diffusivity constant = Cp:hK,J(C2D;'+&P)
desorption rate constant of bound water (Equation (5b))
constant in Equation (34)
film thermal conductivity (Equation (17))
solid film mass transfer coefficient (Equation (5a))
Knudsen diffusivity, I(. = C,(RT, /M,) ''
Knudsen diffusivity, Y, = C,(RT, /M,)OJ
mean Knudsen diffusivity for binary gas mixture,
(k"
= Y.Y. + y
i
m
sample thickness
molecular weight
total flux (N, = N, + Nan)
inen gas flux
808 SADIKOGLU AND LlAPlS

P total pressure in dried layer

Po drying chamber pressure at surface of dried layer
P. partial pressure of water vapor
Pi. partial pressure of inen gas
q energy flux
R universal gas constant
To sample temperature at t=o
T temperature
t time
v velocity of interface
X position of frozen interface
X space coordinate
.Y mole fraction of water vapor
Yi. mole fraction of inen gas

Greek Letters

a thermal diffusivity
E voidage fraction
AH, enthalpy of sublimation of frozen water
AH, enthalpy of vaporization of sorbed water
p viscosity
p density
o Stefan-Boltzmann constant

o initial value at time zero

* equilibrium value

e effective value
f film
in inen
L value at x =L
LP lo,wer plate
m melting
BULK SOLUTION FREEZE-DRYING IN TRAYS

mx mixture
scor scorch
w water vapor
X interfacial value
UP upper plate
o surface value
I dried region
U frozen region

REFERENCES

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 SADIKOGLU AND LlAPlS

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