Antonello A Barresi

Antonello A Barresi
Politecnico di Torino | polito · DISAT - Department of Applied Science and Technology

Ph.D.

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235
Publications
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Publications

Publications (235)
Article
In località Motta, una frazione di Costigliole d’Asti (Piemonte centrale), le piene stagionali del Fiume Tanaro hanno portato alla luce lembi di strati geologici sottostanti. Nei legni fossili affiorati sono state individuate, tramite SEM-EDS, microRaman e PXRD, 8 specie minerali. Poiché l’Astigiano è una provincia povera di minerali, alcune di ess...
Article
Full-text available
Chromatography is a technique widely used in the purification of biopharmaceuticals, and generally consists of several chromatographic steps. In this work, Hydrophobic Interaction Chromatography (HIC) is investigated as a polishing step for the purification of therapeutic proteins. Adsorption mechanisms in hydrophobic interaction chromatography are...
Article
A multi-inlet vortex mixer is used to investigate the co-precipitation of Ni0.8Mn0.1Co0.1(OH)2 particles, largely employed to produce Li-ion battery cathodes. The co-precipitation process is simulated with a population balance model, adopted to describe the experimental findings and gain deeper understanding of the process. Experiments and simulati...
Article
Spray freeze-drying is an emerging manufacturing technology that offers many advantages, including long-term stability, consistent particle size distribution, and enhanced bioavailability. However, its implementation on an industrial scale is still hampered by several technical problems relating to the design of the equipment and the selection of a...
Article
Full-text available
Chromatography is a widely used separation process for purification of biopharmaceuticals that is able to obtain high purities and concentrations. The phenomena that occur during separation, mass transfer and adsorption are quite complex. To better understand these phenomena and their mechanisms, multi-component adsorption isotherms must be investi...
Article
A computational and modeling approach is used to highlight the key factors that affect polymer nanoparticles (NP) formation in flash nano-precipitation (FNP), when the good solvent, e.g., acetone, is replaced by acetonitrile, tetrahydrofuran and tert-butanol. A population balance model is coupled with computational fluid dynamics to study the kinet...
Article
Full-text available
Freezing of the paper material is a way to control the growth of microorganisms and the possibility of “acute” biodeterioration and illness, after accidental events, e.g. flooding. But as the paper-born microorganisms can survive after lyophilisation, they must be controlled also after the drying process. The decision-making about the adoption of p...
Article
Full-text available
Pharmaceutical manufacturing is evolving from traditional batch processes to continuous ones. The new global competition focused on throughput and quality of drug products is certainly the driving force behind this transition which, thus, represents the new challenge of pharmaceutical manufacturing and hence of lyophilization as a downstream operat...
Article
The freezing step plays a key role in the overall economy of the vacuum freeze-drying of pharmaceuticals, since the nucleation and crystal growth kinetics determine the number and size distribution of the crystals formed. In this work, a new mathematical model of the freezing step of a (bio)pharmaceutical solution is developed and validated. Both n...
Research
The aim of this research is to study the transdermal release of caffeine by using polycaprolatone (PCL) nanocapsules. PCL nanocapsules containing caffeine were produced by using a solvent-displacement technique, and consequently, applied on to a knitted cotton fabric. The PCL nanocapsules formulations were prepared at different concentrations of ca...
Article
Wadi Natrun is a depression in northern Egypt that hosts important evaporitic deposits mined for sodium minerals since Pharaonic times, probably around 4000 BC. The authors have studied the mineralogy of Wadi Natrun for about a decade, through extensive laboratory analyses and field work, while recovering excellent specimens of sodium minerals, som...
Article
The association of an active principle with a nanocarrier is known to improve its stability and protect it from external factors. Nevertheless, loading of nanoparticles with highly hydrophilic substances like caffeine remains a tricky issue. In the present study, inverse miniemulsion systems were successfully coupled to UV radiation to synthesize p...
Article
Full-text available
In the field of pharmaceutical technology, significant attention has been paid on exploiting skin as a drug administration route. Considering the structural and chemical complexity of the skin barrier, many research works focused on developing an innovative way to enhance skin drug permeation. In this context, a new class of materials called bio-fu...
Conference Paper
Full-text available
Old paintings are generally characterized by the presence of cracks patterns, formed during the drying process. This network of cracks, known as craquelure, represents a key feature for the authentication of artworks and the discovery of forgery. In this work, an image segmentation approach is used for a quantitative study of cracks patterns in pai...
Article
In this work, a general overview on nanoparticles formation processes is given from both modelling and experimental points of view. The key mechanisms are presented and identified, despite some of them are still under debate. Experiments investigated the effect of different good solvents, as well as the role played by the presence of active princip...
Article
The control of freezing is crucial as it can influence the freeze-drying operation as well as the chemical and physical properties of the lyophilized product such as the specific surface area, dissolution rate, and drug stability. In this review article, we focus on two areas related to lyophilization in the pharmaceutical industry: (1) advances in...
Article
Full-text available
In recent years transdermal drug delivery has aroused significant interest as a sustained and non-invasive way of administering active substances. The advancements of nanotechnology allowed the development of novel pharmaceutical formulations overcoming skin barrier. Furthermore, such nano-system can be combined with conventional fabrics to pave th...
Article
Full-text available
A multi-scale approach can be used to simulate the drying behavior of microparticles in packed-bed. Data outcomes from discrete element method (DEM) and computational fluid dynamics (CFD) simulations can be used to estimate some relevant product characteristics, such as the porosity, tortuosity, voids in the bed and permeability which are required...
Article
This work investigates the behavior during freeze-drying of packing structures formed by spray-frozen microparticles. A multi-scale approach is used to study spray freeze-drying, and in particular, mass transfer during primary drying and its duration. The procedure starts with the generation of realistic packings of microparticles using DEM, and CF...
Article
Full-text available
Flash nanoprecipitation (FNP) is a widely used technique to prepare particulate carriers based on various polymers, and it was proven to be a promising technology for the industrial production of drug loaded nanoparticles. However, up to now, only its application to hydrophobic compounds has been deeply studied and the encapsulation of some strongl...
Article
Full-text available
Monitoring product temperature is mandatory in a freeze-drying process, in particular in the process development stage, as final product quality may be jeopardized when its temperature trespasses a threshold value, that is a characteristic of each product being freeze-dried. To this purpose thermocouples are usually inserted in some of the vials of...
Conference Paper
Full-text available
In a freeze drying process, the freezing step determines the pore size distribution within the product, which, in turn, affects the sublimation rate. Traditionally, pore analysis is carried out on SEM images by means of a manual, time-consuming approach. Here, an image segmentation technique was used to automatize this process and improve its relia...
Article
This manuscript shows how computational models, mainly based on Computational Fluid Dynamics (CFD), can be used to simulate different parts of an industrial freeze-drying equipment and to properly design them; in particular, the freeze-dryer chamber and the duct connecting the chamber with the condenser, with the valves and vanes eventually present...
Article
This manuscript shows how computational models, mainly based on Computational Fluid Dynamics (CFD), can be used to simulate different parts of an industrial freeze-drying equipment and to properly design them; in particular in this part the duct connecting the chamber with the condenser, with its valves, is considered, while the chamber design and...
Article
Computational Fluid Dynamics (CFD) can be used to simulate different parts of an industrial freeze-drying equipment and to properly design them; in particular data concerning the freeze-dryer chamber and the duct connecting the chamber with the condenser, with the valves and vanes eventually present are given here, and can be used to understand the...
Article
The stochastic nature of nucleation makes it difficult to control batch homogeneity in conventional freezing, and this lack of control is in contrast with the current emphasis on Quality by Design. Among the techniques which have been developed to overcome this problem, Vacuum Induced Surface Freezing is probably the most promising for application...
Article
This paper is focused on the synthesis of chitosan-coated polycaprolactone nanoparticles in microreactors and on the freeze-drying of the nanosuspension, to separate the particles from the liquid phase. Nanoparticles were produced in the confined impinging jets mixer (CIJM) and in the multi-inlet vortex mixer (MIVM), using the solvent displacement...
Article
The goal of this paper is to review the available process analytical technology tools for monitoring the batch freeze-drying process for pharmaceuticals. These systems aim evaluating in-line product temperature, sublimation flow rate, and values of some model parameters in such a way that it can be used for in-line or off-line process optimization....
Article
In this work, a novel procedure is presented for the measurement and prediction of pore size distribution of freeze-dried solutions in vials. A method based on segmentation is proposed for determining the size of the pores left by ice crystals, using images obtained by scanning electron microscopy. The original ice crystal size distribution is also...
Article
This paper is focused on the production and characterization of polymeric nanoparticles obtained by nanoprecipitation. The method consisted of using a confined impinging jet mixer (CIJM), circumventing high-energy equipment. Differences between the use of poly-ε-caprolactone (PCL) and poly(lactide-co-glycolide) (PLGA) as concerns particle mean size...
Article
This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in a confined impinging jets reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, e.g. polycaprolactone, is required to support chitosan to obtain a mono-modal p...
Article
Full-text available
Drug delivery by means of transdermal patches raised great interest as a non-invasive and sustained therapy. The present research aimed to design a patch for transdermal delivery of melatonin, which was encapsulated in polycaprolactone (PCL) nanoparticles (NPs) by employing flash nanoprecipitation (FNP) technique. Melatonin-loaded PCL nanoparticles...
Article
In pharmaceutical industry, much attention was given to the problem of prediction of the average size of solvent crystals formed during freezing of pharmaceutical solutions. All the methods proposed in literature to respond to this request are based on empirical laws, while the present work focuses on the development of a mechanistic model. This mo...
Article
The production of producing menthol-loaded poly-ϵ-caprolactone nanoparticles (NPs) for dermal application was investigated. The nanoparticles were produced in three different mixers: a confined impinging jet mixer (CIJM), a two-inlet vortex mixer (VM) and a four-inlet vortex mixer (MIVM), testing their performances in the same operating conditions....
Article
Vacuum Induced Nucleation is often discussed in the context of primary drying performances and its tunability, with the potential to tailor the nucleation temperature to the desired porous structure. Instead, here we investigate its influence on secondary drying dynamics and, in particular, on rate of desorption and vial-to-vial inhomogeneity. So a...
Article
This paper proposes a systematic work process for the rapid determination of the resistance to vapor flow given by products being freeze-dried. This approach couples mathematical modeling and 3D non-destructive X-ray imaging to reconstruct the internal structure of lyophilized samples. Knowledge of the internal structure is fundamental to better un...
Article
Process monitoring is a key issue in pharmaceuticals freeze-drying to evaluate if the limit product temperature is approached, to identify the ending point of the main drying stage, and to estimate the value of some parameters of a mathematical model of the process so that it can be used for cycle optimization. Soft-sensors can be used to this purp...
Article
The segregation of binary mixtures of non-food wheat bran and vegetables at different levels of dryness was studied by simulating different stages of the atmospheric freeze drying by immersion in an adsorbent material (AFD IAM) process. It was characterized using a new set of four indices, which allows to evaluate not only the segregation level, bu...
Conference Paper
The governing equations for heat and mass transfer in porous media depend on packed-bed characteristics. This study proposes the use of computer simulations for the calculation of the porosity, tortuosity and permeability of the packed-bed. In particular, realistic geometric packing arrangements were generated by using a discrete element method par...
Article
Many pharmaceutical products are obtained via freeze-drying of liquid solutions to obtain stable long lasting preparations. The freeze-dry process produces porous cakes whose structure strongly depends on the freezing phase, so that monitoring and optimizing this phase can help both reducing the product cost and insuring its constant quality. Nowad...
Article
The purpose of this study was to develop sustained release systems based on chitosan (CS) and montmorillonite (MMT) for chlorhexidine (CLX). Nanocomposites were prepared by ion-exchange. CLX systems were characterized by X-ray powder diffraction (XRD), thermal analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microsc...
Article
Our analyses of microboudinage structures of piemontite grains embedded within six samples of metachert, one collected from an ultrahigh-pressure (UHP) metamorphic unit at Lago di Cignana in Italy of the Western Alps, and the other five from surrounding high-pressure (HP) metamorphic units in Italy and France, have revealed that the structures are...
Article
Several indices can be found in the literature in order to quantify the mixing degree of two component mixtures in fluidized beds, but none of them is actually capable of describing how a specific component of the mixture is distributed. Many of these indices may be influenced by the experimental procedure used for evaluating the mixture, such as t...
Article
Freeze-drying from mixtures of water and organic solvents has been demonstrated to be beneficial to both product quality and process duration. The aim of this study was to develop a new model-based technology (referred to as valveless monitoring system) that makes it possible to monitor noninvasively the sublimation step in the case of lyophilizati...
Article
This paper is focused on the use of model-based tools to design and optimize in-line a pharmaceuticals freeze-drying process. Two control systems have been compared, a predictive one that uses the pressure rise test to monitor the state of the system and to estimate in-line the values of model parameters, named LyoDriver in previous Literature, and...
Conference Paper
One of the most common processes to produce polymer nanoparticles is to induce self-assembly by using the solvent-displacement method, in which the polymer is dissolved in a “good” solvent and the solution is then mixed with an “anti-solvent”. The polymer ability to self-assemble in solution is therefore determined by its structural and transport p...
Conference Paper
Full-text available
This paper proposes a systematic work process for the rapid determination of the mass transfer resistance to vapour flow through the dry layer, which couples mathematical modelling and 3D non-destructive X-ray imaging to reconstruct the internal structure of lyophilised samples. This method was validated for mannitol-based formulations using variou...
Conference Paper
Full-text available
A multi-scale modelling approach is proposed to better understand the behaviour of the freeze-drying of packed-bed of uniform and non-uniform particles. In particular, realistic geometric packing arrangements have been generated by using a bullet physics engine, while CFD simulation at the pore-scale has been used in order to obtain realistic value...
Chapter
Any change in the synthesis method of polymeric nanoparticles requires a high number of experiments to capture all aspects involved. Understanding the role of transport phenomena, however, makes it possible to relate the particle properties to the operating conditions, and allows extrapolating the results to different systems and operating conditio...
Article
Cotton functionalisation with poly-ε-caprolactone (PCL) micro- and nano-capsules containing menthol was carried out with the aim of introducing a long-lasting refreshing sensation. The preparation of the polymer micro- and nano-capsules was carried out by solvent displacement technique. A confined impinging jets mixer was used in order to ensure fa...
Article
This paper investigates the use of a wavelet image decomposition applied to electron microscope images in order to estimate the mass transfer coefficient of pharmaceutical cakes obtained by freeze-drying. The structure analysis of dried cakes obtained by means of a free-drying process, is a basic step for tuning the process conditions and for monit...
Article
This article deals with the in-line monitoring of a vital freeze-drying process using a soft-sensor that couples the experimental measurement of product temperature with a mathematical model of the process. This tool allows estimating in-line the residual amount of ice in the product and, thus, the duration of the primary drying stage, as well as s...
Article
In this study, a new technology, based on the use of an array of thin-film thermocouples, is proposed for the real-time and non-invasive monitoring of product temperature during a freeze-drying cycle. This array of thin-film thermocouples was demonstrated to give quantitative accurate results without altering the freezing and drying behavior of the...
Conference Paper
ICH Q9 Guidance states that risk management activities are necessary to identify, analyse, evaluate, and, possibly, control the hazards that can affect the quality of a pharmaceutical product across its lifecycle. This paper focuses on the development of a methodology to evaluate the risk related to a freeze-drying process using mathematical modell...
Chapter
This chapter deals with the use of mathematical modeling to get quality-by-design in a freeze-drying process. The target is to identify the design space of the process, i.e., the values of the operating conditions that allow maintaining product temperature below the limit value during primary and secondary drying stages, with a sublimation rate com...
Article
This work deals with the use of a water/tert-butyl alcohol (TBA) system in the manufacturing process of poly-ε-caprolactone (PCL) nanoparticles, namely in the synthesis stage, using the solvent displacement method in a confined impinging jet mixer (CIJM), and in the following freeze-drying stage. The experimental investigation evidenced that the na...
Article
One of the most common processes to produce polymer nanoparticles is the solvent-displacement method, in which the polymer is dissolved in a "good" solvent and the solution is then mixed with an "anti-solvent". The polymer processability is therefore determined by its structural and transport properties in solutions of the pure solvents and at the...
Conference Paper
Full-text available
The Vacuum Induced Nucleation method is here proposed as a mean to promote the uniformity of the batch and make the process more energy efficient. A deeper investigation on the nucleation event is also addressed. Product structure was analysed to evaluate inter-vial homogeneity, while the increasing in product temperature, when ice-nucleation occur...
Article
In this work nanopheres and nanocapsules are precipitated in confined impinging jets mixers through solvent displacement and characterized. Acetone and water are used as solvent and antisolvent together with polymethoxypolyethylene glycol cyanoacrylate-co-hexadecylcyanoacrylate and Miglyol as copolymer and oil, respectively. Characterization is per...
Article
This work is focused on the control of poly-ε-caprolactone nanoparticle characteristics, notably size and size distribution, in both the production and preservation (by using freeze-drying) stages. Nanoparticles were obtained by employing the solvent displacement method in a confined impinging jets mixer. The effect of several operating conditions,...
Article
This paper deals with the problem of monitoring the freeze-drying process of thermo-labile products and particularly tracking the temperature and the position of the interface of sublimation. A novel and affordable way is proposed to estimate the vapor flow rate and, thus, retrieve the parameters of interest. This method is referred to as pressure...
Conference Paper
This paper describes an imaging-based approach for the characterization of the pharmaceutical product structures obtained by freeze-drying. The analysis of the dried cake structure and particularly the estimation of its porosity and permeability, is fundamental for the selection of the optimal process conditions and also for the product quality con...
Conference Paper
This paper describes the development and characterization of a thin film thermocouple array to be used as a non-invasive solution to map the temperature distribution inside small vials used for freeze-drying pharmaceutical chemicals. Pharmaceutical chemicals are often produced by means of freeze-dryers with very good results, even though the slowne...
Article
This paper aims at investigating the design of a freeze-drying cycle taking into account the energy utilization efficiency. A coffee freeze-drying process is considered as case study. The analysis is focused on the primary drying, as this stage accounts for most of the energy consumption. A simplified mathematical model is used to calculate the des...
Article
An experimental nanoparticle preparation process by solvent displacement in passive mixers is considered. The problem under investigation is to estimate the operating conditions in a target device (Mixer B) in order to obtain a product of assigned properties that has already been manufactured in a source device of different geometry (Mixer A). A la...