Microparticulated Hydrochlorothiazide Solid Dispersion: Enhancing Dissolution Properties via Spray Drying

The aim of the present study was to obtain microparticles of hydrochlorothiazide, a diuretic drug that practically insoluble in water, by spray drying and to investigate the influence of process parameters using a three-level, three-factor Box-Behnken design. Process yields, moisture content, particle size, flowability, and solubility were used to evaluate the spray-dried microparticles. The data were analyzed by response surface methodology using analysis of variance. The independent variables studied were outlet temperature, atomization pressure, and drug content. The formulations were prepared using polyvinylpyrrolidone and colloidal silicon dioxide as the hydrophilic carrier and drying aid, respectively. The microparticle yield ranged from 18.15 to 59.02% and resulted in adequate flow (17 to 32 degrees), moisture content between 2.52 to 6.18%, and mean particle size from 45 to 59 mu m. The analysis of variance showed that the factors studied influenced the yields, moisture content, angle of repose, and solubility. Thermal analysis and X-ray diffractometry evidenced no drug interactions or chemical modifications. Photomicrographs obtained by scanning electron microscopy showed spherical particles. The solubility and dissolution rates of hydrochlorothiazide were remarkably improved when compared with pure drug. Therefore, the results confirmed the high potential of the spray-drying technique to obtain microparticulate hydrochlorothiazide with enhanced pharmaceutical and dissolution properties.

Protection of Bifidobacterium lactis and Lactobacillus acidophilus by microencapsulation using spray-chilling

The aim of this study was to produce and evaluate solid lipid microparticles containing Bifidobacterium lactis or Lactobacillus acidophilus. Survival assays were conducted to evaluate the resistance of the probiotics to spray-chilling process, their resistance to simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and their stability during 90 d of storage. The viability of the cells was not affected by microencapsulation. The free and encapsulated cells of B. lactis were resistant to SGF and SIF. The microencapsulation, however, provided protection for L. acidophilus against SGF and SIF. The free and encapsulated microorganisms lost their viability when they were stored at 37 degrees C. However, promising results were obtained when refrigerated and frozen storage was applied. The study indicates that spray-chilling using fat as carrier can be considered an innovative technology and matrix, respectively, for the protection, application and delivery of probiotics. (C) 2012 Elsevier Ltd. All rights reserved.

Microencapsulation of Ketoprofen in Blends of Acrylic Resins by Spray Drying

Microparticles of ketoprofen entrapped in blends of acrylic resins (Eudragit RL 30D and RS 30D) were successfully produced by spray drying. The effects of the proportion ketoprofen : polymer (1: 1 and 1: 3) and of spray-drying parameters (drying gas inlet temperatures of 80 and 100 degrees C; microencapsulating composition feed flow rates of 4 and 6 g/min) on the microparticles properties (drug content, encapsulation efficiency, mean particle size, moisture content, and dissolution behavior) were evaluated. Differential scanning calorimetry (DSC) thermograms and X-ray diffractograms of the spray-dried product, the free drug, and the physical mixture between the free drug and spray-dried composition (blank) were carried out. Microparticles obtained at inlet temperature of 80 degrees C, feed flow rate of 4 g/min, and ketoprofen : acrylic resin ratio of 1: 3 presented an encapsulation efficiency of 88.1%, moisture content of 5.8%, production yield around 50%, and a higher reduction in dissolution rate of the entrapped ketoprofen. Sigmoidal shape dissolution profiles were presented by the spray-dried microparticles. The dissolution profiles were relatively well described by the Weibull model, a showing high coefficient of determination, R-2, and a mean absolute error between experimental and estimated values of between 4.6 and 10.1%.

Engineering Active Pharmaceutical Ingredients by Spray Drying: Effects on Physical Properties and In Vitro Dissolution

Active pharmaceutical ingredients have very strict quality requirements; minor changes in the physical and chemical properties of pharmaceuticals can adversely affect the dissolution rate and therefore the bioavailability of a given drug. Accordingly, the aim of the present study was to investigate the effect of spray drying on the physical and in vitro dissolution properties of four different active pharmaceutical ingredients, namely carbamazepine, indomethacin, piroxicam, and nifedipine. Each drug was dispersed in a solution of ethanol and water (70:30) and subjected to single-step spray drying using similar operational conditions. A complete characterization of the spray-dried drugs was performed via differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), particle size distribution analysis, solubility analysis, and an in vitro dissolution study. The results from the thermal analysis and X-ray diffraction showed that, except for carbamazepine, no chemical modifications occurred as a result of spray drying. Moreover, the particle size distribution of all the spray-dried drugs significantly decreased. In addition, SEM images showed that most of the particles had an irregular shape. There was no significant improvement in the solubility of the spray-dried drugs compared with the unprocessed compounds; however, in general, the dissolution rates of the spray-dried drugs showed a remarkable improvement over their non-spray-dried counterparts. Therefore, the results from this study demonstrate that a single spray-drying step may lead to changes in the physical properties and dissolution characteristics of drugs and thus improve their therapeutic action.

A swirler stabilized combustion chamber for a micro-gas turbine fuelled with natural gas

Micro-gas turbines are a good alternative for on-site power generation, since their operation is very reliable. The possibility of operating with various fuels increases versatility and, as a result, the usage of these devices. Focusing on a performance improvement of a tri-fuel low-cost micro-gas turbine, this work presents investigations of the inner flow of its combustion chamber. The aim of this analysis was the characterization of the flame structure by the temperature field of the chamber inner flow. The chamber was fuelled with natural gas. In the current chamber, a swirler and a reversed flow configuration were utilized to provide flame stabilization. The inner flow investigations were done with numerical analysis, which were compared to experimental data. The analysis of the inner flow was done with numerical simulations, which used the RSM turbulence model. A β-PDF equilibrium model was adopted to account for the turbulent combustion process. Different models of heat transfer were compared. Thermal radiation and specially heat conduction in the liner walls played significant roles on results.

Numerical simulation of an ethanol turbulent spray flame with RANS and diffusion combustion model

A detailed numerical simulation of ethanol turbulent spray combustion on a rounded jet flame is pre- sented in this article. The focus is to propose a robust mathematical model with relatively low complexity sub- models to reproduce the main characteristics of the cou- pling between both phases, such as the turbulence modulation, turbulent droplets dissipation, and evaporative cooling effect. A RANS turbulent model is implemented. Special features of the model include an Eulerian– Lagrangian procedure under a fully two-way coupling and a modified flame sheet model with a joint mixture fraction– enthalpy b -PDF. Reasonable agreement between measured and computed mean profiles of temperature of the gas phase and droplet size distributions is achieved. Deviations found between measured and predicted mean velocity profiles are attributed to the turbulent combustion modeling adopted

The use of metamaterial technology to improve a GTEM chamber

In this work, metamaterial patterns are applied to a GTEM – Gigahertz Transverse Electromagnetic Chamber to improve and give flexibility to its frequency response. The main goal is to achieve a better frequency resonance regardless the dimensions of the original chamber. Therefore, a comparison between the CLL – Capacitively Loaded Loop and Fractal metamaterial technology for these purposes, is done. Experimental results are compared to the simulated ones

Photocatalytic activity of nanostructured anatase coatings obtained by cold gas spray

[EN] This article describes a photocatalytic nanostructured anatase coating deposited by cold gas spray (CGS) supported on titanium sub-oxide (TiO22x) coatings obtained by atmospheric plasma spray (APS) onto stainless steel cylinders. The photocatalytic coating was homogeneous and preserved the composition and nanostructure of the starting powder. The inner titanium sub-oxide coating favored the deposition of anatase particles in the solid state. Agglomerated nano-TiO2 particles fragmented when impacting onto the hard surface of the APS TiO22x bond coat. The rough surface provided by APS provided an ideal scenario for entrapping the nanostructured particles, which may be adhered onto the bond coat due to chemical bonding; a possible bonding mechanism is described. Photocatalytic experiments showed that CGS nano-TiO2 coating was active for photodegrading phenol and formic acid under aqueous conditions. The results were similar to the performance obtained by competitor technologies and materials such as dip-coating P25 photocatalysts. Disparity in the final performance of the photoactive materials may have been caused by differences in grain size and the crystalline composition of titanium dioxide.

Numerical simulations of magma chamber dynamics at Campi Flegrei, and associated seismicity, deformation and gravity changes

Understanding the complex relationships between quantities measured by volcanic monitoring network and shallow magma processes is a crucial headway for the comprehension of volcanic processes and a more realistic evaluation of the associated hazard. This question is very relevant at Campi Flegrei, a volcanic quiescent caldera immediately north-west of Napoli (Italy). The system activity shows a high fumarole release and periodic ground slow movement (bradyseism) with high seismicity. This activity, with the high people density and the presence of military and industrial buildings, makes Campi Flegrei one of the areas with higher volcanic hazard in the world. In such a context my thesis has been focused on magma dynamics due to the refilling of shallow magma chambers, and on the geophysical signals detectable by seismic, deformative and gravimetric monitoring networks that are associated with this phenomenologies. Indeed, the refilling of magma chambers is a process frequently occurring just before a volcanic eruption; therefore, the faculty of identifying this dynamics by means of recorded signal analysis is important to evaluate the short term volcanic hazard. The space-time evolution of dynamics due to injection of new magma in the magma chamber has been studied performing numerical simulations with, and implementing additional features in, the code GALES (Longo et al., 2006), recently developed and still on the upgrade at the Istituto Nazionale di Geofisica e Vulcanologia in Pisa (Italy). GALES is a finite element code based on a physico-mathematical two dimensional, transient model able to treat fluids as multiphase homogeneous mixtures, compressible to incompressible. The fundamental equations of mass, momentum and energy balance are discretised both in time and space using the Galerkin Least-Squares and discontinuity-capturing stabilisation technique. The physical properties of the mixture are computed as a function of local conditions of magma composition, pressure and temperature.The model features enable to study a broad range of phenomenologies characterizing pre and sin-eruptive magma dynamics in a wide domain from the volcanic crater to deep magma feeding zones. The study of displacement field associated with the simulated fluid dynamics has been carried out with a numerical code developed by the Geophysical group at the University College Dublin (O’Brien and Bean, 2004b), with whom we started a very profitable collaboration. In this code, the seismic wave propagation in heterogeneous media with free surface (e.g. the Earth’s surface) is simulated using a discrete elastic lattice where particle interactions are controlled by the Hooke’s law. This method allows to consider medium heterogeneities and complex topography. The initial and boundary conditions for the simulations have been defined within a coordinate project (INGV-DPC 2004-06 V3_2 “Research on active volcanoes, precursors, scenarios, hazard and risk - Campi Flegrei”), to which this thesis contributes, and many researchers experienced on Campi Flegrei in volcanological, seismic, petrological, geochemical fields, etc. collaborate. Numerical simulations of magma and rock dynamis have been coupled as described in the thesis. The first part of the thesis consists of a parametric study aimed at understanding the eect of the presence in magma of carbon dioxide in magma in the convection dynamics. Indeed, the presence of this volatile was relevant in many Campi Flegrei eruptions, including some eruptions commonly considered as reference for a future activity of this volcano. A set of simulations considering an elliptical magma chamber, compositionally uniform, refilled from below by a magma with volatile content equal or dierent from that of the resident magma has been performed. To do this, a multicomponent non-ideal magma saturation model (Papale et al., 2006) that considers the simultaneous presence of CO2 and H2O, has been implemented in GALES. Results show that the presence of CO2 in the incoming magma increases its buoyancy force promoting convection ad mixing. The simulated dynamics produce pressure transients with frequency and amplitude in the sensitivity range of modern geophysical monitoring networks such as the one installed at Campi Flegrei . In the second part, simulations more related with the Campi Flegrei volcanic system have been performed. The simulated system has been defined on the basis of conditions consistent with the bulk of knowledge of Campi Flegrei and in particular of the Agnano-Monte Spina eruption (4100 B.P.), commonly considered as reference for a future high intensity eruption in this area. The magmatic system has been modelled as a long dyke refilling a small shallow magma chamber; magmas with trachytic and phonolitic composition and variable volatile content of H2O and CO2 have been considered. The simulations have been carried out changing the condition of magma injection, the system configuration (magma chamber geometry, dyke size) and the resident and refilling magma composition and volatile content, in order to study the influence of these factors on the simulated dynamics. Simulation results allow to follow each step of the gas-rich magma ascent in the denser magma, highlighting the details of magma convection and mixing. In particular, the presence of more CO2 in the deep magma results in more ecient and faster dynamics. Through this simulations the variation of the gravimetric field has been determined. Afterward, the space-time distribution of stress resulting from numerical simulations have been used as boundary conditions for the simulations of the displacement field imposed by the magmatic dynamics on rocks. The properties of the simulated domain (rock density, P and S wave velocities) have been based on data from literature on active and passive tomographic experiments, obtained through a collaboration with A. Zollo at the Dept. of Physics of the Federici II Univeristy in Napoli. The elasto-dynamics simulations allow to determine the variations of the space-time distribution of deformation and the seismic signal associated with the studied magmatic dynamics. In particular, results show that these dynamics induce deformations similar to those measured at Campi Flegrei and seismic signals with energies concentrated on the typical frequency bands observed in volcanic areas. The present work shows that an approach based on the solution of equations describing the physics of processes within a magmatic fluid and the surrounding rock system is able to recognise and describe the relationships between geophysical signals detectable on the surface and deep magma dynamics. Therefore, the results suggest that the combined study of geophysical data and informations from numerical simulations can allow in a near future a more ecient evaluation of the short term volcanic hazard.

Polymer controlled mineralization of zinc phosphate hydrates and applications in corrosion protection, catalysis and biomedicine

ZUSAMMENFASSUNG Die Tauglichkeit von Hybridmaterialien auf der Basis von Zinkphosphathydrat-Zementen zum Einsatz als korrosionshemmende anorganische Pigmente oder zur prothetischen und konservierenden Knochen- und Zahntherapie wird weltweit empirisch seit den neunziger Jahren intensiv erforscht. In der vorliegenden Arbeit wurden zuerst Referenzproben, d.h. alpha-und beta-Hopeite (Abk. a-,b-ZPT) dank eines hydrothermalen Kristallisationsverfahrens in wässerigem Milieu bei 20°C und 90°C hergestellt. Die Kristallstruktur beider Polymorphe des Zinkphosphattetrahydrats Zn3(PO4)2  4 H2O wurde komplett bestimmt. Einkristall-strukturanalyse zeigt, daß der Hauptunterschied zwischen der alpha-und beta-Form des Zinkphosphattetrahydrats in zwei verschiedenen Anordnungen der Wasserstoffbrücken liegt. Die entsprechenden drei- und zweidimensionalen Anordnungen der Wasserstoffbrücken der a-und b-ZPT induzieren jeweils unterschiedliches thermisches Verhalten beim Aufwärmen. Während die alpha-Form ihr Kristallwasser in zwei definierten Stufen verliert, erzeugt die beta-Form instabile Dehydratationsprodukt. Dieses entspricht zwei unabhängigen, aber nebeneinander ablaufenden Dehydratationsmechanismen: (i) bei niedrigen Heizraten einen zweidimensionalen Johnson-Mehl-Avrami (JMA) Mechanismus auf der (011) Ebene, der einerseits bevorzugt an Kristallkanten stattfindet und anderseits von existierenden Kristalldefekten auf Oberflächen gesteuert wird; (ii) bei hohen Heizraten einem zweidimensionalen Diffusionsmechanismus (D2), der zuerst auf der (101) Ebene und dann auf der (110) Ebene erfolgt. Durch die Betrachtung der ZPT Dehydratation als irreversibele heterogene Festkörperstufenreaktion wurde dank eines „ähnlichen Endprodukt“-Protokolls das Dehydratationsphasendiagramm aufgestellt. Es beschreibt die möglichen Zusammenhänge zwischen den verschiedenen Hydratationszuständen und weist auf die Existenz eines Übergangszustandes um 170°C (d.h. Reaktion b-ZPT  a-ZPT) hin. Daneben wurde auch ein gezieltes chemisches Ätzverfahren mit verdünnten H3PO4- und NH3 Lösungen angewendet, um die ersten Stufe des Herauslösens von Zinkphosphat genau zu untersuchen. Allerdings zeigen alpha- und beta-Hopeite charakteristische hexagonale und kubische Ätzgruben, die sich unter kristallographischer Kontrolle verbreitern. Eine zuverlässige Beschreibung der Oberfächenchemie und Topologie konnte nur durch AFM und FFM Experimente erfolgen. Gleichzeitig konnte in dieser Weise die Oberflächendefektdichte und-verteilung und die Volumenauflösungsrate von a-ZPT und b-ZPT bestimmt werden. Auf einem zweiten Weg wurde eine innovative Strategie zur Herstellung von basischen Zinkphosphatpigmenten erster und zweiter Generation (d.h. NaZnPO4  1H2O und Na2ZnPO4(OH)  2H2O) mit dem Einsatz von einerseits oberflächenmodifizierten Polystyrolatices (z.B. produziert durch ein Miniemulsionspolymerisationsverfahren) und anderseits von Dendrimeren auf der Basis von Polyamidoamid (PAMAM) beschritten. Die erhaltene Zeolithstruktur (ZPO) hat in Abhängigkeit von steigendem Natrium und Wassergehalt unterschiedliche kontrollierte Morphologie: hexagonal, würfelförmig, herzförmig, sechsarmige Sterne, lanzettenförmige Dendrite, usw. Zur quantitativen Evaluierung des Polymereinbaus in der Kristallstruktur wurden carboxylierte fluoreszenzmarkierte Latices eingesetzt. Es zeigt sich, daß Polymeradditive nicht nur das Wachstum bis zu 8 µm.min-1 reduzierten. Trotzdem scheint es auch als starker Nukleationsbeschleuniger zu wirken. Dank der Koordinationschemie (d.h. Bildung eines sechszentrigen Komplexes L-COO-Zn-PO4*H2O mit Ligandenaustausch) konnten zwei einfache Mechanismen zur Wirkung von Latexpartikeln bei der ZPO Kristallisation aufgezeigt werden: (i) ein Intrakorona- und (ii) ein Extrakorona-Keimbildungsmechanismus. Weiterhin wurde die Effizienz eines Kurzzeit- und Langzeitkorrosionschutzes durch maßgeschneiderte ZPO/ZPT Pigmente und kontrollierte Freisetzung von Phosphationen in zwei Näherungen des Auslösungsgleichgewichts abgeschätzt: (i) durch eine Auswaschungs-methode (thermodynamischer Prozess) und (ii) durch eine pH-Impulsmethode (kinetischer Prozess. Besonders deutlich wird der Ausflösungs-Fällungsmechanismus (d.h. der Metamorphismus). Die wesentliche Rolle den Natriumionen bei der Korrosionshemmung wird durch ein passendes zusammensetzungsabhängiges Auflösungsmodell (ZAAM) beschrieben, das mit dem Befund des Salzsprühteste und der Feuchtigkeitskammertests konsistent ist. Schließlich zeigt diese Arbeit das herausragende Potential funktionalisierter Latices (Polymer) bei der kontrollierten Mineralisation zur Herstellung maßgeschneiderter Zinkphosphat Materialien. Solche Hybridmaterialien werden dringend in der Entwicklung umweltfreundlicher Korrosionsschutzpigmente sowie in der Dentalmedizin benötigt.

Design and fluid dynamic analysis of a custom drip chamber in a medical disposable device

Negli ultimi anni, parallelamente allo sviluppo di calcolatori elettronici sempre più performanti, la fluidodinamica computazionale è diventata uno strumento di notevole utilità nell’analisi dei flussi e nello sviluppo di dispositivi medici. Quando impiegate nello studio di flussi di fluidi fisiologici, come il sangue, il vantaggio principale delle analisi CFD è che permettono di caratterizzare il comportamento fluidodinamico senza dover eseguire test in-vivo/in-vitro, consentendo quindi notevoli vantaggi in termini di tempo, denaro e rischio derivante da applicazioni mediche. Inoltre, simulazioni CFD offrono una precisa e dettagliata descrizione di ogni parametro di interesse permettendo, già in fase di progettazione, di prevedere quali modifiche al layout garantiranno maggiori vantaggi in termini di funzionalità. Il presente lavoro di tesi si è posto l’obiettivo di valutare, tramite simulazioni CFD, le performances fluidodinamiche del comparto sangue “camera venosa” di un dispositivo medico monouso Bellco impiegato nella realizzazione di trattamenti di emodialisi. Dopo una panoramica del contesto, è presentata una breve descrizione della disfunzione renale e dei trattamenti sostitutivi. Notevole impegno è stato in seguito rivolto allo studio della letteratura scientifica in modo da definire un modello reologico per il fluido non-Newtoniano preso in considerazione e determinarne i parametri caratteristici. Il terzo capitolo presenta lo stato dell’arte delle apparecchiature Bellco, rivolgendosi con particolare attenzione al componente “cassette” del dispositivo monouso. L’analisi fluidodinamica del compartimento “camera venosa” della cassette, che sarà presa in considerazione nei capitoli quinto e sesto, si inserisce nell’ambito della riprogettazione del dispositivo attualmente in commercio: il quarto capitolo si incentra sul suo nuovo design, ponendo specifico interesse sul layout della camera venosa di nuova generazione. Per lo studio dei flussi che si sviluppano internamente ad essa ci si è avvalsi del modulo CFD del software COMSOL multiphysics® (versione 5.0); la definizione del modello implementato e della tipologia di studio effettuato sono presi in considerazione nel quinto capitolo. Le problematiche di maggior impatto nella realizzazione di un trattamento di emodialisi sono l’emolisi e la coagulazione del sangue. Nell'evenienza che si verifichino massivamente occorre infatti interrompere il trattamento con notevoli disagi per il paziente, per questo devono essere evitate. Nel sesto capitolo i risultati ottenuti sono stati esaminati rivolgendo particolare attenzione alla verifica dell’assenza di fenomeni che possano portare alle problematiche suddette.

Microincapsulazione di nanoparticelle di argento tramite tecnica spray-freeze-drying

Per limitare gli effetti tossici delle Ag-NPs, si è pensato che esse possano essere utilizzate in forma di microincapsulati, in quanto le microcapsule possono avere una certa velocità di rilascio sotto specifiche condizioni. Incapsulando quindi le Ag-NPs, posso ottenere un rilascio controllato di esse, in modo da ottenere una concentrazione di esse utile allo scopo per cui vengono impiegate, evitando un sovradosaggio che non porterebbe alcun beneficio ma solo a una maggior probabilità di causare effetti tossici.

Conjunctival Proliferation After a Mild Pepper Spray Injury in a Young Child

PURPOSE To report a case of conjunctival proliferation in a 2.5-year-old boy after initial evidence of a mild chemical injury after ocular exposure to pepper spray (oleoresin capsicum). METHODS Case report with ophthalmologic and histologic findings. RESULTS A child presented with mild conjunctival injection and chemosis without any corneal erosion after direct exposure to pepper spray. Three weeks later, a significant conjunctival proliferation was found at the limbus, which was refractory to treatment with topical corticosteroids. Finally, proliferative tissue was surgically excised without clinical recurrence during 2 months of follow-up. CONCLUSIONS We hypothesize that the young age of the patient may have been an important factor for the severe conjunctival proliferation in comparison to a mainly uncomplicated course of pepper spray injuries in most adults. We recommend the use of topical antiinflammatory treatment even in apparently mild pepper spray injuries, especially in young children.