Roman Peczalski

Freeze-Drying of Pharmaceutical Proteins in Vials: Modeling of Freezing and Sublimation Steps

The commercial finite element code FEMLAB was used to perform two-dimensional axisymmetric simulations of the temperature profiles and the moving front velocities of standard BSA (bovine serum albumin)-based formulations used to stabilize pharmaceutical proteins during the freeze-drying process. The simulations were validated with both experimental and numerical approaches. In an initial step, the heat transfer phenomena taking place during the cooling of liquid solutions was studied in commercial size glass vials without freezing or sublimation. Then, this model was extended and validated for the freezing process of aqueous BSA-based solutions encountered in the industrial freeze-drying processes with the same vials in order to confirm the identified values of the different thermal conductances between the product and the shelf and between the product and the surroundings. Finally, the conductances between the product and the shelf and between the vial and the surroundings thus determined were used in a dynamic sublimation model with two zones and a moving sublimation front similar to the ones previously proposed in the literature. The simulations showed a satisfactory agreement between experimental and simulated data. The results of this study demonstrated that the freeze-drying process of pharmaceutical proteins in glass vials for standard industrial operating conditions was mainly controlled by the heat transfer from the shelf and the surroundings to the product sublimation front.

A theoretical model for ice primary nucleation induced by acoustic cavitation.

The modelling and simulation of ice nucleation triggered by acoustic cavitation was addressed in this study. The objective was to evaluate the number of nuclei generated by a single gas bubble and afterwards by a multi-bubble system as function of the acoustic pressure (ultrasound wave amplitude) and supercooling level (liquid temperature). According to our calculations, the nucleation could be initiated with moderated acoustic pressure amplitude (around one bar) even at low supercooling levels (around few degrees). These results may provide a sound basis for the control of ice crystal size and morphology which is a key issue in industrial freezing and freeze-drying processes.

Experimental Study and Modeling of Crystalline Powders Vacuum Contact Drying with Intermittent Stirring

Modified literature models were successfully applied to simulate the evolution of the average solvent content (ethanol) of potassium chloride bed during vacuum contact drying with intermittent stirring. Our new modeling approach incorporated the following modifications: the introduction of a jacketed vessel heat transfer coefficient and an accumulation term for the heating wall temperature; the application of alternate static bed and stirred bed conditions; and modeling of all the three drying phases, namely the constant rate phase, the transition phase, and the falling rate phase. Moreover, several validation experiments were carried out with different operating conditions to identify the values of the unknown model parameter. The optimal stirring conditions were investigated by calculating total drying times for different sequences of stirring and no stirring periods.

Theoretical model of ice nucleation induced by acoustic cavitation. Part 1: Pressure and temperature profiles around a single bubble

This paper deals with the inertial cavitation of a single gas bubble in a liquid submitted to an ultrasonic wave. The aim was to calculate accurately the pressure and temperature at the bubble wall and in the liquid adjacent to the wall just before and just after the collapse. Two different approaches were proposed for modeling the heat transfer between the ambient liquid and the gas: the simplified approach (A) with liquid acting as perfect heat sink, the rigorous approach (B) with liquid acting as a normal heat conducting medium. The time profiles of the bubble radius, gas temperature, interface temperature and pressure corresponding to the above models were compared and important differences were observed excepted for the bubble size. The exact pressure and temperature distributions in the liquid corresponding to the second model (B) were also presented. These profiles are necessary for the prediction of any physical phenomena occurring around the cavitation bubble, with possible applications to sono-crystallization.

Theoretical model of ice nucleation induced by inertial acoustic cavitation. Part 2: Number of ice nuclei generated by a single bubble

In the preceding paper (part 1), the pressure and temperature fields close to a bubble undergoing inertial acoustic cavitation were presented. It was shown that extremely high liquid water pressures but quite moderate temperatures were attained near the bubble wall just after the collapse providing the necessary conditions for ice nucleation. In this paper (part 2), the nucleation rate and the nuclei number generated by a single collapsing bubble were determined. The calculations were performed for different driving acoustic pressures, liquid ambient temperatures and bubble initial radius. An optimal acoustic pressure range and a nucleation temperature threshold as function of bubble radius were determined. The capability of moderate power ultrasound to trigger ice nucleation at low undercooling level and for a wide distribution of bubble sizes has thus been assessed on the theoretical ground.

Combined Convective and Microwave Drying of Agglomerated Sand: Internal Transfer Modeling with the Gas Pressure Effect

In order to improve the industrial drying (hot air and microwave) of inserts made of agglomerated sand, a comprehensive internal heat and water transfer model has been proposed. In this model, the internal gas phase pressure effect was made perfectly explicit, especially the phenomena of liquid and vapour transfer by filtration and of liquid expulsion at the surface. This model was validated on the basis of the experimental mean water content and core temperature curves for drying trials at different microwave powers. Then, it was used for comparing the drying time and the internal pressure level calculated for four particular processes: a standard process with high temperature air applied all over the time, a strong process with high power microwaves applied all over, and two processes which alternate the two heating modes. It was demonstrated that the combined and alternative processes provide a real possibility for faster drying with less internal pressure and thus with less cracking risk. The microwaves should be applied only in the first hour of the process and with decreasing power. The decrease of the drying time was around 30% with regard to the hot air standard process.

Drying-Induced Cracking of Abrasive Rings:Risk Prediction and Process Optimisation by Numerical Simulation

ABSTRACT The dependence of the mechanical stresses distribution on the water content and temperature profiles has been numerically investigated in a porous unsaturated hygroscopic abrasive agglomerate of annular shape. The thermophysical, kinetic and mechanical properties of the abrasive agglomerate were determined experimentally. The simulations have been applied to unfired abrasive rings convective drying optimisation by fitting operating conditions in order to avoid cracks formation.

Hydro-Thermo-Mechanical Model for Highly Deformable Product during Convective Drying

The aim of this work was to simulate in 1D, the spatio-temporal evolution of the moisture content, the temperature and the mechanical stress within a highly deformable and saturated product during convective drying. The hydro-thermal model, written in a fixed coordinate system, consisted of solid mass balance equation, moisture transfer diffusion/advection equation and heat transfer conduction/advection equation. These equations were coupled by the solid phase velocity terms due to hydric shrinkage. Convective boundary conditions completed this set of equations. The hydro-thermal model had been merged with a static mechanical model which was based on the hypothesis of an elastic behavior, of a plane deformation and of an ideal shrinkage. The hydro-thermo-mechanical model had been applied to a parallelepipedical potato sample. Its thickness was small compared to the other dimensions, in order to observe an unidirectional drying and a negligible shear stress case. The transport and equilibrium properties of the product required for the modelling were determined from previous experiments which were independent of the drying trials.

Crystallization and freezing processes assisted by power ultrasound

Power ultrasound may be used to control crystal properties in solutions and melts. The first part of this chapter concerns the thermodynamics and kinetics of crystallization. The second part reviews several studies dealing with ultrasound-assisted crystallization or freezing processes. The influence of operating conditions (dissipated acoustic power or intensity, frequency, duration, ultrasonic device) on the properties of crystals and the process rate is discussed. The third part investigates elementary mechanisms (temperature, pressure, diffusive and chemical effects) underlying the sonocrystallization process according to the literature as well as on the ground of our own results. A special paragraph is devoted to ice crystallization in supercooled aqueous solutions.

2-D Hydro-Viscoelastic Model for Convective Drying of Highly Deformable Saturated Product

The aim of this work was to simulate in two-dimensions the spatio-temporal evolution of the moisture content, the temperature, and the mechanical stress within a highly deformable and water saturated product during convective drying. The material under study was an elongated potato sample with a square section placed in hot air flow. A comprehensive hydro-thermal model had been merged with a mechanical model, assuming a viscoelastic material, a plane deformation, and an isotropic linear hydric-shrinkage of the sample. This model was validated on the basis of the average water content and core temperature curves for drying trials under different operating conditions. The material viscoelastic properties were measured by means of stress relaxation tests at different water contents. The viscoelastic behavior was described by a generalized Maxwell model whose parameters were correlated to water content. The simulations of the spatio-temporal distributions of mechanical stress were performed and interpreted in terms of product potential damage. The sample shape was also predicted all aver the drying process with reasonable accuracy.