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Drying Technology
An International Journal
Volume 40, 2022 - Issue 15
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Articles

Model development for the design of control strategies of the primary drying of lyophilization in vials

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Pages 3292-3309 | Received 21 Oct 2021, Accepted 23 Dec 2021, Published online: 17 Jan 2022
 

Abstract

This paper proposes a development to reformulate the fundamental equations of primary drying into a linear-based representation to support control design. The model is expressed by transfer functions with variable gains that incorporate analytical relations derived from a phenomenological model. The time constants denote the dynamics of the heating/cooling and vacuum systems. Compared to fundamental equations, this approach simplifies the development and implementation of well-established control algorithms. The quality of the proposed representation is illustrated in the design of a control system using two different strategies: model predictive control and a feedback controller with proportional-integral action. The simulation case study allows assessing the performance of both designs with regard to cycle time reduction and robustness under parametric disturbances. Results evidence that the proposed model is detailed enough to provide accuracy in a simplified way, facilitating the implementation of in-line control strategies, which in turn enable significant reductions of drying time.

Nomenclature
Ap=

inner cross-sectional area of the vial (m2)

Av=

outer cross-sectional area of the vial (m2)

c1, c2, c3=

empirical coefficients for the calculation of Pw,a

Cp=

specific heat capacity of ice (J)

FT=

transfer function of the equivalent dynamics of the heating system

FP=

transfer function of the equivalent dynamics of the vacuum system

h=

sublimation front position (m)

ḣ=

front position rate (m s–1)

L=

total thickness of the frozen layer (m)

Hp=

prediction horizon

Hc=

control horizon

ΔHs=

heat of sublimation of ice (J kg–1)

Jw=

heat flux to the product (J m–2 s–1)

k1, k2, k3=

empirical coefficients for the calculation of Qv

k4, k5, k6=

empirical coefficients for the calculation of Rp

K=

gains of the LPV model

Kc=

proportional gain of the PI

m=

total mass of the product (kg)

Nw=

sublimation flux of water vapor (kg m–2 s–1)

P=

chamber pressure (Pa)

Pw=

temperature-dependent water vapor saturation pressure (Pa)

Qv=

overall heat transfer coefficient (J m–2 s–1 K–1)

Rp=

dried layer resistance (m s–1)

TB=

temperature of the product at the vial bottom (K)

Tc=

critical temperature of the product (K)

Ti=

temperature of the product at the interface (K)

Ts=

temperature of the shelf (K)

u=

system input

Wu=

input increment weight

Wy=

set-point tracking weight

y=

system output

Greek symbols
λ=

thermal conductivity (J m–1 s–1 K–1)

ρ=

density (kg m–3)

τs=

time constant of heating system (s)

τp=

time constant of vacuum system(s)

τi=

integral time constant of the PI (s)

Superscripts and subscripts
̂=

estimated value

a=

approximate

d=

dried layer

f=

frozen layer

min=

minimum value

max=

maximum value

r=

reference

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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