An analysis of the lyophilization process using a sorption‐sublimation model and various operational policies

Abstract

The freeze-drying process is studied under various operational policies through the use of a sorption-sublimation model. The operational policy that provides the shortest drying times keeps the pressure at its lowest value. The upper and lower heating plates are independently controlled so that the material constraints are encountered and held throughout the free water removal phase.Under certain conditions, and for the case of samples of small thickness, the sorbed water profiles may have segments whose bound water concentrations are higher than those at the start of the free water removal phase. It is shown that the criterion used in terminating the freeze-drying process is of extreme importance, since it may lead to an undesirable sorbed water profile which may deteriorate the quality of the dried product. M. J. MILLMAN, SCOPECertain biological materials, pharmaceuticals, biochemical products, and foodstuffs which may not be heated even to moderate temperatures in ordinary drying, are freeze-dried. Recent developments in biotechnology and biochemical engineering (Hill and Hirtenstein, 1983) have established the importance of lyophilization-freeze-drying-in biochemical processing.As a rule, freeze-drying produces the highest quality product obtainable by any drying method (Goldblith et al., 1975;Mellor, 1978). Prominent factors are the structural rigidity of the product, which facilitates rapid and almost complete rehydration at a later time, little loss of flavor and aroma, and minimization of degradative reactions which normally occur in ordinary drying processes, such as nonenzymatic browning, protein denaturation, and enzymatic reactions.However, freeze-drying is an expensive form of drying because of the slow drying rates and the use of vacuum. Thus, it is essential to develop operational policies which would reduce the drying times by improving the drying rates.The interactions in the variables of the freeze-drying process are complex, and an experimental approach of examining the various operational policies is tedious, expensive, and timeconsuming. But the experiment will finally confirm or disprove the validity of operational policies suggested by theoretical work, and which are supposed to improve or minimize the drying times. A mathematical model which can predict known freezedrying experimental results accurately, can be used in the analysis of the freezedrying process and in the examination of various operational policies which may maximize the drying rates. This work develops a sorption-sublimation model which is used to study operational policies that may significantly reduce the drying times. This model is also used to examine the effects on the bound water profiles of the criteria employed to end the terminal drying phase. Skim milk was used as a model material.The development of bound water profiles incorporates an important factor for optimization policies for quality retention in freeze-drying. CONCLUSIONS AND SIGNIFICANCEA sorption-sublimation model is presented and used to simulate the fr...

Numerical Simulation for Freeze Drying of Skimmed Milk with Moving Sublimation Front using Tri-Diagonal Matrix Algorithm

“…The top surface is assumed as x = 0, the downward direction as the positive direction for analysis and the bottom surface is taken as x = L. The physical parameters of skimmed milk are taken from literatures (Millman et al 1985;Sadikoglu and Liapis 1997;Mascarenhas et al 1997). In the industries, the milk product was initially frozen by a deep freezer and then into the freeze dryer where the condenser temperature was maintained at -80 ºC (Roos 1992).…”

Modeling of the primary and secondary drying stages of the freeze drying of pharmaceutical products in vials: Numerical results obtained from the solution of a dynamic and spatially multi-dimensional lyophilization model for different operational policies

“…The constitutive equations used in this work for the mass flux vectors are from the dusty-gas model (Jackson, 1977;Mason and Malinauskas, 1983;Millman et al, 1985;Gloor et al, 1987), and their form for the water and inert gas species present in the pores of the dried layer are:…”

3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying

“…Several mono-and multi-dimensional mathematical models of freeze-drying were developed in the past years [16][17][18][19][20][21][22][23][24][25], but only few of them explore the sources of the atypical heat flow rate in edge vials. In most of the studies [19,20,22,25], the heat transfer by radiation from the door and walls of the drying chamber was considered completely responsible of the higher product temperature observed in edge vials.…”