Pickering Emulsions Based in Inorganic Solid Particles: From Product Development to Food Applications.

Pickering emulsions (PEs) have attracted attention in different fields, such as food, pharmaceuticals and cosmetics, mainly due to their good physical stability. PEs are a promising strategy to develop functional products since the particles' oil and water phases can act as carriers of active compounds, providing multiple combinations potentiating synergistic effects. Moreover, they can answer the sustainable and green chemistry issues arising from using conventional emulsifier-based systems. In this context, this review focuses on the applicability of safe inorganic solid particles as emulsion stabilisers, discussing the main stabilisation mechanisms of oil-water interfaces. In particular, it provides evidence for hydroxyapatite (HAp) particles as Pickering stabilisers, discussing the latest advances. The main technologies used to produce PEs are also presented. From an industrial perspective, an effort was made to list new productive technologies at the laboratory scale and discuss their feasibility for scale-up. Finally, the advantages and potential applications of PEs in the food industry are also described. Overall, this review gathers recent developments in the formulation, production and properties of food-grade PEs based on safe inorganic solid particles.

The potential of almonds, hazelnuts, and walnuts SFE-CO2 extracts as sources of bread flavouring ingredients.

Nuts have been part of the human diet since our early ancestors, and their use goes beyond nutritional purposes, for example, as aromatic sources for dairy products. This work explores the potential of almond (Prunus dulcis (Mill.) DA Webb), hazelnut (Corylus avellana L.), and walnut (Juglans regia L.) extracts as sources of food flavouring agents, suggesting a new added-value application for lower quality or excess production fruits. The extracts were obtained by supercritical fluid extraction with carbon dioxide and characterized by: quantification of the volatile fraction by HS-SPME GC-MS; sensory perception and description; and cytotoxicity against Vero cells. All extracts revealed potential as flavouring ingredients due to terpene abundance. No significant differences were observed for the minimal sensory perception, in which the odour threshold values ranged from 8.3 × 10-4 to 6.9 × 10-3 µg·mL-1 for walnuts and almonds extracts, respectively. In contrast, the cytotoxic potential differed significantly among the extracts, and P. dulcis extract presented lower cytotoxicity. Notes as woody, fresh, and green were identified in the volatile intensifiers obtained from the P. dulcis extract. Thus, almond extract was identified as the most promising ingredient to increase the sensory value of food products, namely bread. This potential was verified by an increase in the odour perception of bread after adding 4 µL of extract to each 100 g of bread dough. The quantified eucalyptol and d-limonene terpenes - found in the P. dulcis extract - have improved the release of the pleasant and natural volatile compounds from bread crust and crumb compared to the control bread chemical and sensory profiles.

Saponins as Natural Emulsifiers for Nanoemulsions.

The awareness of sustainability approaches has focused attention on replacing synthetic emulsifiers with natural alternatives when formulating nanoemulsions. In this context, a comprehensive review of the different types of saponins being successfully used to form and stabilize nanoemulsions is presented, highlighting the most common natural sources and biosynthetic routes. Processes for their extraction and purification are also reviewed altogether with the recent advances for their characterization. Concerning the preparation of the nanoemulsions containing saponins, the focus has been initially given to screening methods, lipid phase used, and production procedures, but their characterization and delivery systems explored are also discussed. Most experimental outcomes showed that the saponins present high performance, but the challenges associated with the saponins' broader application, mainly the standardization for industrial use, are identified. Future perspectives report, among others, the emerging biotechnological processes and the use of byproducts in a circular economy context.

Chemical and organoleptic properties of bread enriched with Rosmarinus officinalis L.: The potential of natural extracts obtained through green extraction methodologies as food ingredients.

The potential of R. officinalis L. (RO) extracts as a source of aromas was accessed by hydrodistillation (HD) and supercritical fluid extraction using carbon dioxide (SFE-CO2), followed by a series of analysis: quantification by GC-MS, sensory perception and description, and cytotoxicity against Vero cells. The extracts shown abundancy of α-pinene, eucalyptol, S-verbenone and camphor, contributing for the green, fresh, citric, and woody as main sensory notes. The odour threshold (ODT) value (less than 3.0 × 10-3 µg·mL-1) and the cytotoxic potential (ca. 220 µg∙mL-1) defined the concentration range for food application. The most promising extract was added to bread doughs and the final volatile profile was characterised by GC-MS through HS-SPME over time. Among the 34 compounds found, furfural showed an evident contribution in the bread crust aroma, which persisted over four hours of storage, contributing to a pleasant bread fragrance according to the evaluators. This study aims to represent a stepping stone for the use of natural aromas as ingredients for the development of innovative food products.

Obtaining Aromatic Extracts from Portuguese Thymus mastichina L. by Hydrodistillation and Supercritical Fluid Extraction with CO2 as Potential Flavouring Additives for Food Applications.

Humans often respond to sensory impulses provided by aromas, and current trends have generated interest in natural sources of fragrances rather than the commonly used synthetic additives. For the first time, the resulting aroma of a selected culture of Thymus mastichina L. was studied as a potential food ingredient. In this context, dried (DR) and fresh (FR) samples were submitted to carbon dioxide (CO2) supercritical extraction (SFE) and hydrodistillation (HD) methods. The extracts were characterised according to their volatile composition by GC-MS, cytotoxicity against a non-tumour cell culture, and sensory attributes (odour threshold and olfactive descriptors). The most abundant aromas were quantified, and the analysis performed by GC-MS revealed an abundance of terpenoids such as thymol chemotype, followed by the precursors α-terpinene and p-cymene. DR and FR extracts (EX) obtained from SFE-CO2 show the highest content of thymol, achieving 52.7% and 72.5% of the isolated volatile fraction. The DR essential oil (EO) contained the highest amount of terpenoids, but it was also the most cytotoxic extract. In contrast, SFE-CO2 products showed the lowest cytotoxic potential. Regarding FR-OE, it had the lowest extraction yield and composition in aroma volatiles. Additionally, all samples were described as having green, fresh and floral sensory notes, with no significant statistical differences regarding the odour detection threshold (ODT) values. Finally, FR-EX of T. mastichina obtained by SFE-CO2 presented the most promising results regarding food application.

Microalgae-Derived Pigments: A 10-Year Bibliometric Review and Industry and Market Trend Analysis.

Microalgae productive chains are gaining importance as sustainable alternatives to obtain natural pigments. This work presents a review on the most promising pigments and microalgal sources by gathering trends from a 10-year bibliometric survey, a patents search, and an industrial and market analysis built from available market reports, projects and companies' webpages. The performed analysis pointed out chlorophylls, phycocyanin, astaxanthin, and ß-carotene as the most relevant pigments, and Chlorella vulgaris, Spirulina platensis, Haematococcus pluvialis, and Dunaliella salina, respectively, as the most studied sources. Haematococcus is referred in the highest number of patents, corroborating a high technological interest in this microalga. The biorefinery concept, investment in projects and companies related to microalgae cultivation and/or pigment extraction is increasingly growing, particularly, for phycocyanin from Spirulina platensis. These pieces of evidence are a step forward to consolidate the microalgal pigments market, which is expected to grow in the coming years, increasing the prospects of replacing synthetic pigments by natural counterparts.

Formulation and Optimization of Nanoemulsions Using the Natural Surfactant Saponin from Quillaja Bark.

Replacing synthetic surfactants by natural alternatives when formulating nanoemulsions has gained attention as a sustainable approach. In this context, nanoemulsions based on sweet almond oil and stabilized by saponin from Quillaja bark with glycerol as cosurfactant were prepared by the high-pressure homogenization method. The effects of oil/water (O/W) ratio, total surfactant amount, and saponin/glycerol ratio on their stability were analyzed. The formation and stabilization of the oil-in-water nanoemulsions were analyzed through the evaluation of stability over time, pH, zeta potential, and particle size distribution analysis. Moreover, a design of experiments was performed to assess the most suitable composition based on particle size and stability parameters. The prepared nanoemulsions are, in general, highly stable over time, showing zeta potential values lower than -40 mV, a slight acid behavior due to the character of the components, and particle size (in volume) in the range of 1.1 to 4.3 µm. Response surface methodology revealed that formulations using an O/W ratio of 10/90 and 1.5 wt% surfactant resulted in lower particle sizes and zeta potential, presenting higher stability. The use of glycerol did not positively affect the formulations, which reinforces the suitability of preparing highly stable nanoemulsions based on natural surfactants such as saponins.

Removal of bromate from drinking water using a heterogeneous photocatalytic mili-reactor: impact of the reactor material and water matrix.

The main goal of this study was to evaluate the removal of bromate from drinking water using a heterogeneous photocatalytic mili-photoreactor, based on NETmix technology. The NETmix mili-reactor consists of a network of channels and chambers imprinted in a back slab made of acrylic (AS) or stainless steel (SSS) sealed, through mechanical compression and o-rings, with an UVA-transparent front borosilicate glass slab (BGS). A plate of UVA-LEDs was placed above the BGS window. TiO2-P25 thin films were immobilized on the BGS (back-side illumination, BSI) or SSS (front-side illumination, FSI) by using a spray deposition method. The photoreduction rate of a 200 µg L-1 (1.56 µM) BrO3- solution was assessed taking into account the following: (i) catalyst film thickness, (ii) catalyst coated surface and illumination mechanism (BSI or FSI), (iii) solution pH, (iv) type and dose of sacrificial agent (SA), (v) reactor material, and (vi) water matrix. In acidic conditions (pH 3.0) and in the absence of light/catalyst/SA, 28% and 36% of BrO3- was reduced into Br- only by contacting with AS and SSS during 2-h, respectively. This effect prevailed during BSI experiments, but not for FSI ones since back SSS was coated with the photocatalyst. The results obtained have demonstrated that (i) the molar rate of disappearance of bromates was similar to the molar rate of formation of bromides; (ii) higher BrO3- reduction efficiencies were reached in the presence of an SA using the FSI at pH 3.0; (iii) formic acid ([BrO3-]:[CH2O2] molar ratio of 1:3) presented higher performance than humic acids (HA = 1 mg C L-1) as SA; (iv) high amounts of HA impaired the BrO3- photoreduction reaction; (v) SSS coated catalyst surface revealed to be stable for at least 4 consecutive cycles, keeping its photonic efficiency. Under the best operating conditions (FSI, 18 mL of 2% wt. TiO2-P25 suspension, pH 3.0), the use of freshwater matrices led to (i) equal or higher reaction rates, when compared with a synthetic water in the absence of SA, and (ii) lower reaction rates, when compared with a synthetic water containing formic acid with a [BrO3-]:[CH2O2] molar ratio of 1:3. Notwithstanding, heterogeneous TiO2 photocatalysis, using the NETmix mili-reactor can be used to promote the reduction of BrO3- into Br-, attaining concentrations below 10 µg L-1 (guideline value) after 2-h reaction. Graphical Abstract .

Ozonation and ozone-enhanced photocatalysis for VOC removal from air streams: Process optimization, synergy and mechanism assessment.

The present work evaluates ozone driven processes (O3, O3/UVC, O3/TiO2/UVA) in the NETmix mili-photoreactor, as a cost-effective alternative for the removal of volatile organic compounds (VOCs) from air streams, using n-decane as a model pollutant. The network of channels and chambers of the mili-photoreactor was coated with a TiO2-P25 thin film, resulting in a catalyst coated surface per reactor volume of 990 m2 m-3. Ozone and n-decane streams were fed to alternate chambers of the mili-photoreactor, promoting a good contact between O3/n-decane/catalyst. Initially, direct reaction between n-decane and ozone (ozonation) was assessed for different O3/n-decane (O3/dec) feed molar ratios and total feed flow rates. Under the best conditions, ozonation process achieved total n-decane conversion (below the limit of detection), yielding a reaction rate (rdec) of 6.8 µmol min-1 or 6.7 mmol m-3reactor s-1. However, the low reactivity of ozone with the degradation by-products resulted in a quite poor mineralization (~10%). For the O3/UVC system, an increase on relative humidity from 7 to 40% slight improved the n-decane oxidation rate, mainly associated with the generation of HO from the reaction of active oxygen radicals (O) and water molecules. A strong synergistic effect was observed when coupling TiO2/UVA photocatalysis with ozonation (O3/TiO2/UVA), enhancing substantially the mineralization of n-decane molecules up to 100% under O3/dec feed molar ratio of 15, photonic flux of 2.67 ±â€¯0.03 J s-1 and a residence time of 2.0 s. Different reaction intermediates were detected for O3, TiO2/UVA and O3/TiO2/UVA oxidative systems, indicating the participation of different oxidant species (O3, HO, O, etc.).

Intensification of heterogeneous TiO2 photocatalysis using the NETmix mili-photoreactor under microscale illumination for oxytetracycline oxidation.

This study focuses on the intensification of heterogeneous TiO2 photocatalysis for the removal of a contaminant of emerging concern (CEC), oxytetracycline (OTC), as a polishing step of urban wastewaters, using an innovative NETmix mili-photoreactor under UVA-LEDs illumination. The effect of catalyst coated surface per reactor volume and the illumination mechanism, back-side (BSI) or front-side (FSI) irradiation, on OTC oxidation were evaluated. For that, a thin film of photocatalyst was uniformly deposited on the front borosilicate slab (BS) (BSI mechanism; 333 m2catalyst m-3reactor) or on the network of channels and chambers imprinted in the back stainless-steel slab (SSS) (FSI mechanism; 989 m2catalyst m-3reactor) using a spray system. OTC removal was also assessed as a function of TiO2 film thickness immobilized on both slabs. The photocatalyst reactivity in combination with photoreactor was significantly enhanced (3.4 times) from 0.64 to 2.19 mmolOTC m-3illuminated reactor volume s-1, when considering the BSI and FSI mechanisms, respectively. In addition, the influence of UVA-LEDs intensity on OTC oxidation rate was investigated. UVA-LEDs plates were placed on the top of the NETmix borosilicate window. Moreover, the effect of water matrix was assessed using a secondary effluent from an urban wastewater treatment plant fortified with OTC. OTC oxidation rate was only inhibited in about 1.3 times in the presence of the real matrix, showing the ability of the NETmix to overcome matrix effects due to its unique characteristics. Catalyst film stability over four consecutive reaction cycles was evaluated using synthetic and real matrices fortified with OTC.

Selecting the best piping arrangement for scaling-up an annular channel reactor: An experimental and computational fluid dynamics study.

This study is focused on the selection of the best piping arrangement for a pilot scale annular channel reactor intended for the remediation of waters and wastewaters. Two annular channel reactors composed of a single UV lamp and distinct piping arrangements were considered: (i) a novel reactor with tangential inlet/outlet pipes - the FluHelik reactor, and (ii) a conventional Jets reactor. These two reactors were manufactured at lab scale and characterized in terms of residence time distribution (RTD), radiant power and ability to degrade aqueous solutions spiked with a model compound - 3-amino-5-methylisoxazole (AMI) - by H2O2/UVC and UVC processes. Computational fluid dynamics (CFD) simulations were used to assess the hydrodynamics, RTD and UV radiation intensity distribution of both reactors at pilot scale. In general, experimental results at lab scale revealed quite similar RTDs, radiant powers and AMI degradation rates for both reactors. On the other hand, CFD simulations at pilot scale revealed the generation of a helical motion of fluid around the UVC lamp in the FluHelik reactor, inducing: (i) a longer contact time between fluid particles and UV light, (ii) more intense dynamics of macromixing as a result of larger velocity gradients, turbulent intensities and dispersion of RTD values around the peak, and (iii) a more homogeneous UV radiation distribution. In addition, the design of the FluHelik reactor can favor the implementation of various reactors in series, promoting its application at industrial scale. The FluHelik reactor was chosen for scaling-up. A pre-pilot scale treatment unit containing this reactor was constructed and its feasibility was proven.

Intensifying heterogeneous TiO2 photocatalysis for bromate reduction using the NETmix photoreactor.

This work focuses on the intensification of BrO3- (200 µg L-1) reduction by TiO2-assisted heterogeneous photocatalysis, using the NETmix mili-photoreactor illuminated by UVA light-emitting diodes (UVA-LEDs). The mili-photoreactor was assembled in two configurations: i) catalyst deposition on the channels and chambers of a back stainless steel slab (SSS) and ii) catalyst deposition on the front borosilicate glass slab (BGS), allowing the study of front-side (FSI) and back-side (BSI) illumination mechanisms, respectively. The BrO3- reduction rate in aqueous solution was assessed as a function of: i) pH; ii) dissolved oxygen (DO); iii) addition of formic acid (CH2O2) as a sacrificial agent (SA); iv) photocatalyst film thickness; v) illumination mechanism; vi) irradiation intensity; vii) temperature; and viii) water matrix. Higher BrO3- reduction rates were observed using the FSI mechanism and lower pH values. Nitrogen injection (to eliminate DO) did not significantly improve the reaction rate and the addition of CH2O2 had a negative effect at pH 6.5. Neither temperature nor irradiance increase showed a considerable improvement on the reduction rate. Moreover, TiO2 film remains stable for at least 13 consecutive reactions without significant catalyst leaching. The chemically pre-treated fresh water (FW) matrix negatively affected the reaction rate when compared with the synthetic water (SW), under the best operational conditions (SSS: pH = 5.5, 287 mg of TiO2, 25 °C, SA absence, [DO] = 232-263 µM). This was associated with the presence of both inorganic and organic matter at much higher concentrations than BrO3-. Notwithstanding, heterogeneous TiO2 photocatalysis, using the NETmix mili-photoreactor, was successfully applied to fresh water, achieving [BrO3-] < 10 µg L-1 (guideline value) after 2-hour reaction.

Overcoming limitations in photochemical UVC/H2O2 systems using a mili-photoreactor (NETmix): Oxytetracycline oxidation.

This study focuses on the intensification of a photochemical UVC/H2O2 system using a mili-photoreactor (NETmix) for a better and faster elimination of oxytetracycline (OTC) from urban wastewater. This mili-photoreactor comprises a network of small cylindrical chambers and prismatic transport channels sealed by a UVC transparent quartz slab allowing unique properties. Since light has a profound effect on the photochemical process, UVC photons distribution over the reaction medium was investigated using a multiple UVC lamp design (4, 6 or 11 W) allocated in parallel or perpendicular to the solution movement. In addition, the effect of other operating variables, such as oxidant dosage (100-900 mg L-1), oxidant feed configuration (single entry or continuous multi-injection) and flow rate (50-100 L h-1) was studied. A kinetic model able to describe the OTC oxidation by the UVC/H2O2 photochemical system in the mili-photoreactor was also developed. Moreover, matrix effect was evaluated by spiking OTC in a secondary effluent from an urban WWTP. In this case, OTC degradation was inhibited in about 2 to 3 times due to the presence of organic/inorganic substances (soluble and particulate), inherent to the real matrix, that act as scavenger of oxidant species and as UVC light filter. The NETmix mili-photoreactor presented high photochemical space time yield (PSTY) values when compared with a conventional tubular photoreactor. This highlights the NETmix capacity to enhance UVC/H2O2 processes through an homogeneous light distribution over the entire reaction medium.

Application of a micro-meso-structured reactor (NETmix) to promote photochemical UVC/H2O2 processes - oxidation of As(iii) to As(v).

A micro-meso-structured reactor (NETmix) was used for the first time to promote photochemical UVC/H2O2 processes. The NETmix photoreactor consists of a network of chambers and channels, where the liquid flows, sealed with a quartz slab with high UVC transparency. Due to the small size of channels and chambers, the NETmix presents a uniform irradiance through the entire reactor depth, short molecular diffusion distances and large specific interfacial areas, maximizing the pollutant/oxidant contact. In this study, the NETmix photoreactor was evaluated for As(iii) oxidation to As(v) using a photochemical UVC/H2O2 system. The effect of the UVC lamp power (4, 6 or 11 W), the number of UVC lamps (2 or 3 lamps) and the UVC lamp layout (parallel or perpendicular to the flow direction) was evaluated, in order to ensure uniform irradiation of the entire reaction mixture. The optimum H2O2 concentration for each light distribution system was also evaluated. At the best configuration, 3 lamps of 11 W positioned parallel to the flow direction, total As(iii) oxidation ([As(iii)]0 = 1.33 × 10-2 mM) was achieved in 15 min with an absorbed photon flux density of 1.9 × 10-1 einstein per m3 per s. Significant differences were highlighted between the photon flux actually received in the photoreactor and the radiant power emitted by the lamp. A kinetic model able to represent the As(iii) oxidation employing UVC radiation and H2O2 in a micro-meso-structured reactor was presented. The photochemical space time yield (PSTY) values obtained for the micro-meso-structured reactor are higher than for conventional batch reactors, showing that the NETmix technology can be a good solution for application in photochemical processes.

Strategies to reduce mass and photons transfer limitations in heterogeneous photocatalytic processes: Hexavalent chromium reduction studies.

The current work presents different approaches to overcome mass and photon transfer limitations in heterogeneous photocatalytic processes applied to the reduction of hexavalent chromium to its trivalent form in the presence of a sacrificial agent. Two reactor designs were tested, a monolithic tubular photoreactor (MTP) and a micro-meso-structured photoreactor (NETmix), both presenting a high catalyst surface area per reaction liquid volume. In order to reduce photon transfer limitations, the tubular photoreactor was packed with transparent cellulose acetate monolithic structures (CAM) coated with the catalyst by a dip-coating method. For the NETmix reactor, a thin film of photocatalyst was uniformly deposited on the front glass slab (GS) or on the network of channels and chambers imprinted in the back stainless steel slab (SSS) using a spray system. The reaction rate for the NETmix photoreactor was evaluated for two illumination sources, solar light or UVA-LEDs, using the NETmix with the front glass slab or/and back stainless steel slab coated with TiO2-P25. The reusability of the photocatalytic films on the NETmix walls was also evaluated for three consecutive cycles using fresh Cr(VI) solutions. The catalyst reactivity in combination with the NETmix-SSS photoreactor is almost 70 times superior to one obtained with the MTP.

Antiangiogenic compounds: well-established drugs versus emerging natural molecules.

Angiogenesis is the natural and physiologic process of growing blood vessels from pre-existing ones. Pathological angiogenesis occurs when the precise balance of all the molecular pathways that regulate angiogenesis is disrupted, and this process is a critical step in many diseases, including cancer. A limited number of antiangiogenic synthetic drugs have been developed. However, due to toxicity and side effects issues, the search for alternative to existing drugs is ongoing. In this sense, natural molecules obtained from plants or macrofungi, have demonstrated extraordinary potential in the treatment of angiogenesis-related pathologies, specially taking into consideration its absence or very low toxicity, when compared to synthetic drugs. Using natural compounds as potential angiogenesis modulators is thus a promising field of research, supporting the creation of novel therapies able to reduce the use of drugs and associated side effects. In this review, the current status of antiangiogenic drugs and the wide variety of natural extracts and molecules with antiangiogenic capacities, as well as the angiogenesis molecular pathways and therapeutic targets, are presented. Finally, the challenges that need to be overcome in order to increase the use of natural compounds for clinical purposes are discussed.

Continuous flow photo-Fenton treatment of ciprofloxacin in aqueous solutions using homogeneous and magnetically recoverable catalysts.

The degradation of ciprofloxacin was studied in aqueous solutions by using a continuous flow homogeneous photo-Fenton process under simulated solar light. The effect of different operating conditions on the degradation of ciprofloxacin was investigated by changing the hydrogen peroxide (0-2.50 mM) and iron(II) sulphate (0-10 mg Fe L(-1)) concentrations, as well as the pH (2.8-10), irradiance (0-750 W m(-2)) and residence time (0.13-3.4 min) of the process. As expected, the highest catalytic activity in steady state conditions was achieved at acidic pH (2.8), namely 85 % of ciprofloxacin conversion, when maintaining the other variables constant (i.e. 2.0 mg L(-1) of iron(II), 2.50 mM of hydrogen peroxide, 1.8 min of residence time and 500 W m(-2) of irradiance). Additionally, magnetite magnetic nanoparticles (ca. 20 nm of average particle size) were synthesized, characterized and tested as a possible catalyst for this reaction. In this case, the highest catalytic activity was achieved at natural pH, namely a 55 % average conversion of ciprofloxacin in 1.8 min of residence time and under 500 W m(-2). Some of the photocatalytic activity was attributed to Fe(2+) leaching from the magnetic nanoparticles to the solution.

A highly reproducible continuous process for hydroxyapatite nanoparticles synthesis.

This work presents a continuous process for producing hydroxyapatite nanoparticles (NanoXIM) in a network reactor, NETmix, fed by a calcium solution, a phosphorus solution and an alkaline solution. Hydroxyapatite is considered a biomaterial, used as: food additives and nutritional supplements; bone graft for bone replacement, growth and repair; biocements and coating of metallic implant. Some of the most recent applications include their use in cosmetics, toothpaste and in esthetical treatments for diminishing wrinkles by stimulating conjunctive tissue formation. The proposed process enables the micromixing control, which is essential to form nanometric structures, but it is also a determining factor in the crystals purity, crystallinity and morphology. The reactants distribution scheme at the inlet of the reactor and along the reactor, performed continuously or varying in time, is also a crucial factor to programme the properties of reactant media along the reactor, such as the pH, the supersaturation degree, the Ca/P molar ratio, and the temperature. The calcium phosphate nanoparticles suspension that exits the reactor is submitted to further aging, separation, drying, sintering and milling processes.