Olive Oil-Based Oleogel as Fat Replacer in a Sponge Cake: A Comparative Study and Optimization.

Oleogels (defined as structured solid-like materials with a high amount of oil entrapped within a three-dimensional network of gelator molecules) represent a healthy alternative to fats that are rich in saturated and trans fatty acids. Given its fatty acids composition (oleic, linoleic, and linolenic acids), olive oil is an excellent candidate for the use of oleogels in the food industry. In this study, a D-optimal mixture design was employed to optimize the replacement of butter with olive oil-based oleogel in a type of sponge cake formulation: the plum cake. In addition, emulsifiers and whey proteins were used as recipe ingredients to extend the product's shelf life by delaying staling phenomena and mold growth. In the experimental design, oleogel, emulsifier, and whey protein variables were set as the ingredients that change in specific ranges, while hardness, porosity, water activity, and moistness were used to characterize the obtained formulations. The experimental data of each response were fitted through polynomial regression models with the aim of identifying the best plum cake formulation. The results revealed that the best mixture was the formulation containing 76.98% olive oil-based oleogel, 7.28% emulsifier E471, and 15.73% whey protein. We stored the optimized plum cake for 3 months at room temperature and then checked for any hardness and moistness changes or mold spoilage.

Effect of Load Spatial Configuration on the Heating of Chicken Meat Assisted by Radio Frequency at 40.68 MHz.

Food heating assisted by radio frequencies has been industrially applied to post-harvest treatment of grains, legumes and various kind of nuts, to tempering and thawing of meat and fish products and to post-baking of biscuits. The design of food processes based on the application of radiofrequencies was often based on rules of thumb, so much so that their intensification could lead significant improvements. One of the subjects under consideration is the shape of the food items that may influence their heating assisted by radiofrequency. In this work, a joint experimental and numerical study on the effects of the spatial configuration of a food sample (chicken meat shaped as a parallelepiped) on the heating pattern in a custom RF oven (40.68 MHz, 50 Ohm, 10 cm electrodes gap, 300 W) is presented. Minced chicken breast samples were shaped as cubes (4 × 4 × 4 cm3) to be organized in different loads and spatial configurations (horizontal or vertical arrays of 2 to 16 cubes). The samples were heated at two radiofrequency operative power levels (225 W and 300 W). Heating rate, temperature uniformity and heating efficiency were determined during each run. A digital twin of the experimental system and process was developed by building and numerically solving a 3D transient mathematical model, taking into account electromagnetic field distribution in air and samples and heat transfer in the food samples. Once validated, the digital tool was used to analyze the heating behavior of the samples, focusing on the most efficient configurations. Both experiments and simulations showed that, given a fixed gap between the electrodes (10 cm), the vertically oriented samples exhibited a larger heating efficiency with respect to the horizontally oriented ones, pointing out that the gap between the top electrode and the samples plays a major role in the heating efficiency. The efficiency was larger (double or even more; >40% vs. 10−15%) in thicker samples (built with two layers of cubes), closer to the top electrode, independently from nominal power. Nevertheless, temperature uniformity in vertical configurations was poorer (6−7 °C) than in horizontal ones (3 °C).

On-Road Detection of Driver Fatigue and Drowsiness during Medium-Distance Journeys.

BACKGROUND: The detection of driver fatigue as a cause of sleepiness is a key technology capable of preventing fatal accidents. This research uses a fatigue-related sleepiness detection algorithm based on the analysis of the pulse rate variability generated by the heartbeat and validates the proposed method by comparing it with an objective indicator of sleepiness (PERCLOS). Methods: changes in alert conditions affect the autonomic nervous system (ANS) and therefore heart rate variability (HRV), modulated in the form of a wave and monitored to detect long-term changes in the driver's condition using real-time control. Results: the performance of the algorithm was evaluated through an experiment carried out in a road vehicle. In this experiment, data was recorded by three participants during different driving sessions and their conditions of fatigue and sleepiness were documented on both a subjective and objective basis. The validation of the results through PERCLOS showed a 63% adherence to the experimental findings. Conclusions: the present study confirms the possibility of continuously monitoring the driver's status through the detection of the activation/deactivation states of the ANS based on HRV. The proposed method can help prevent accidents caused by drowsiness while driving.

Microwave Treatments of Cereals: Effects on Thermophysical and Parenchymal-Related Properties.

Dielectric heating is one of the most interesting techniques for pest disinfestation. However, most of the literature works give information about the ability of microwave treatments at different power-time conditions to kill insects; less is given about the analysis of matrices structural properties and heat transport. Accordingly, the aim of this work is to investigate the effect of microwave treatments, applied for pest disinfestation, on heat transport behavior and physical/structural properties, such as water uptake capability, mineral losses, texture change, and germination capability, of most consumed cereals in human diet, such as weak wheat, durum wheat, and corn. Two different radiative treatments were performed: one in time-temperature conditions capable of inactivating the weed fauna, and the other at high temperatures of ~150 °C, simulating uncontrolled treatments. Heat transport properties were measured and showed to keep unvaried during both effective and uncontrolled microwave treatments. Instead, grain physical properties were worsened when exposed to high temperatures (reduction of germination ability and texture degradation). The achieved results, on the one hand, provide new structural and heat transport data of cereals after microwave treatments, actually not present in the literature, and on the other, they confirm the importance of correctly performing microwave treatments for an effective disinfestation without affecting matrices physical properties and nutritional features.

On the relevance of thermophysical characterization in the microwave treatment of legumes.

This study is focused on the characterization of the thermal behavior and physical properties of the most consumed legumes in the daily diet such as beans, lentils and chickpeas. Because of a lack of information in the literature about the effect of microwave treatments on legumes, characterization protocols have been applied before and after subjecting them to microwave irradiation suitable for pest disinfestation. The effects of two different radiative treatments, one suitable for inactivating the infesting fauna and the other simulating uncontrolled treatments, characterized by very high temperatures, were tested. The impacts of microwave treatments on legumes, in terms of thermal behavior, germination capability, tannin and total polyphenol composition and other physical properties (water uptake capability, texture change, mineral losses), after typical soaking cooking processes, are also studied. The thermal properties of the examined legumes were found to be comparable for all samples. Similarly, no significant differences in antinutritional factors, polyphenol and tannin content among all samples were detected. From the structural point of view, samples exposed to high temperatures showed texture degradation and in turn, loss of mineral nutrients during soaking processes. Moreover, their germination capability was drastically reduced. These latter results highlighted why it is important to correctly perform the radiative microwave process in order to both ensure effective and safe disinfestation and avoid nutritional value loss and the worsening of physical properties.

HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties.

Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various fields such as pharmaceuticals, biomaterials, agriculture, food, water purification. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45-2mm in size, was fully characterized. Results showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45-2mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.

New Preparative Approaches for Micro and Nano Drug Delivery Carriers.

The full success of pharmacological therapies is strongly depending on the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards specific organs or tissues, to allow the maintenance of drug concentration within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings. In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.

Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis.

The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force-penetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.

Droplet size prediction in the production of drug delivery microsystems by ultrasonic atomization.

Microencapsulation processes of drugs or other functional molecules are of great interest in pharmaceutical production fields. Ultrasonic assisted atomization is a new technique to produce microencapsulated systems by mechanical approach. It seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this paper the groundwork of atomization is briefly introduced and correlations to predict droplet size starting from process parameters and material properties are presented.

Analysis of size correlations for microdroplets produced by ultrasonic atomization.

Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested.

In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery.

OBJECTIVE: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs). METHODOLOGY: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract. RESULTS: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer. CONCLUSION: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.

Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis.

In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.

Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique.

A method to produce biopolymeric (alginate) microparticles by ultrasonic assisted atomization, previously developed, has been applied to the production of microparticles loaded with a small active molecule (theophylline). Fine loaded alginate droplets have been cross-linked with divalent ions to produce microparticles. Once produced, the particles have been separated by centrifugation or filtration and then they have been dried. Drug release has been evaluated by dissolution tests, dissolving the dried particles in acidic solution at pH 1 for a given time and then at pH 7 to simulate the stomach and intestinal environment, respectively. The encapsulation efficiency and the drug loading have been investigated and the operating conditions have been changed to clarify the role of the transport phenomena on the overall process. To increase the drug loading, shorter separation time and better network's structure were identified as the key operating parameters to allow the process to gain interest from a practical point of view.

Intensifying the microencapsulation process: ultrasonic atomization as an innovative approach.

In this review, new approaches to the microencapsulation processes, widely used in the manufacturing of pharmaceutical products, are discussed focusing the attention on the emerging ultrasonic atomization technique. Fundamentals and novel aspects are presented, and advantages of ultrasonic atomization in terms of intensification and low energy requests are emphasized.

Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation.

An engineering approach to biomedical sciences: advanced strategies in drug delivery systems production.

Development and optimization of novel production techniques for drug delivery systems are fundamental steps in the "from the bench to the bedside" process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drug delivery systems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported.

A combined technique based on prilling and microwave assisted treatments for the production of ketoprofen controlled release dosage forms.

In this study the feasibility of joining prilling and microwave (MW) assisted treatments as combined technique to produce controlled release alginate beads was tested. Beads were produced by prilling (laminar jet break-up) using different polymer concentrations and loaded with ketoprofen, a slightly soluble non-steroidal anti-inflammatory BCS class II drug characterized by low melting point. MW assisted treatments applied using different irradiating conditions were performed as drying/curing step. The effect of formulation conditions and process variables on drying kinetics, particle micromeritics, shape, surface and inner characteristics of the matrix as well as drug loading and drug release behaviour was studied (USP pH change method). The properties of MW dried particles were compared to those dehydrated by convective methods (room conditions and tray oven 105°C). Results showed that MW dried ketoprofen loaded beads were obtained in a very narrow dimensional range retaining shape and size distribution of the hydrates particles. Compared to the traditional drying methods, MW treatments were able to strongly increase drying rate of the hydrated beads achieving faster and controllable dehydration kinetics. Moreover, different regimes of irradiation affected structural properties of the particles such as matrix porosity as well as the solid state of the loaded drug. DSC, X-ray and FTIR analyses indicated complex chemical interactions between the drug and polymer matrix induced by MW, related with the regime of irradiation, that contributes to the differences in release profiles. In fact, MW treatments under different time and irradiating regimes are able to modulate drug release from alginate beads; high levels of irradiation led to beads suitable for immediate release oral dosage forms whereas the lowest regime of irradiation led to beads that achieved a prolonged/sustained release of the drug till 8h in simulated intestinal medium. This study showed that prilling in combination with microwave treatments is a useful and simple tandem technique to prepare dextran-based dried beads.

Enteric micro-particles for targeted oral drug delivery.

This work is focused on production of enteric-coated micro-particles for oral administration, using a water-in-oil-in-water solvent evaporation technique. The active agent theophylline was first encapsulated in cellulose acetate phthalate (CAP), a pH-sensitive well-known polymer, which is insoluble in acid media but dissolves at neutral pH (above pH 6). In this first step, CAP was chosen with the aim optimizing the preparation and characterization methods. The desired release pattern has been obtained (low release at low pH, higher release at neutral pH) but in presence of a low encapsulation efficiency. Then, the CAP was replaced by a novel-synthesized pH-sensitive poly(methyl methacrylate-acrylic acid) copolymer, poly(MMA-AA). In this second step, the role of two process parameters was investigated, i.e., the percentage of emulsion stabilizer (polyvinyl alcohol, PVA) and the stirring power for the double emulsion on the encapsulation efficiency. The encapsulation efficiency was found to increase with PVA percentage and to decrease with the stirring power. By increasing the PVA content and by decreasing the stirring power, a high stable double emulsion was obtained, and this explains the increase in encapsulation efficiency found.

On the behavior of HPMC/Theophylline matrices for controlled drug delivery.

Design of systems for oral controlled release of drug could take advantages from the knowledge of which phenomena take place. In this work matrices obtained by powders compression (50:50, hydroxypropyl methylcellulose, a swelling hydrogel, and theophylline, a model drug) were immersed in water at 37 degrees C, allowing the water uptake and the drug release by lateral surface, confining the cylindrical matrices between glass slides. The tablets, after given immersion times, were withdrawn, cut in several annuli, and subsequently analyzed for the drug and the water concentration radial profiles. The data confirmed the pseudo-diffusive nature of the process, allowing to give a deep insight into the drug release process from swellable hydrogel matrices. In particular, it was confirmed the presence of nonhomogeneous gel layer, rich in water and poor in drug, with a profile of drug concentration which agrees well with a pseudo-diffusion phenomenon.

A general code to predict the drug release kinetics from different shaped matrices.

This work deals with the modeling of drug release from solid pharmaceutical systems (matrices) for oral delivery. The attention was paid to the behavior of matrices made of hydrogels and drug, and the modeling was devoted to reproduce all the relevant phenomena (water up-take, gel swelling, diffusivity increase, drug diffusion and polymer erosion). Thus, the transient mass balances (for both drug and water), with the proper initial and boundary conditions were written, and a generalized numerical code was formulated; it is able to describe several geometries (slab, sphere, infinite and finite cylinders; this latter was done by an approximation which reduces the 2D problem to an 1D scheme). The main phenomena observed in drug delivery from hydrogel-based matrix, i.e. polymer swelling and erosion, were taken into account. The code was validated by comparison with analytical solutions, available for some simplified situation, and then it was tested with some experimental data taken from literature.