Sulbactam pivoxil powder attributes and compatibility study with excipients

Background: Sulbactam pivoxil is an irreversible β-lactamase inhibitor that can be used with β-lactam antibiotics to improve antibacterial therapy by the oral route. Relevant properties of this drug for pharmaceutical manufacturing are not available in the open literature. In this work, a solid-state characterization of sulbactam pivoxil at the molecular, particle, and bulk levels was performed. Results: Particles exhibited a mean diameter of about 350 μm, irregular shape crystals, and good flow properties. This work presents for the first time the crystal structure of this β-lactamase inhibitor obtained by X-ray diffraction analysis. Fourier-transform infrared results showed the characteristic bands of aliphatic hydrocarbons and ester groups. The differential scanning calorimetry curve exhibited a sharp endothermic peak at 109 °C corresponding to sulbactam pivoxil melting. The thermogravimetric curve revealed a mass loss at 184 °C associated with a decomposition process. This powder showed a moisture content of 0.34% and a water activity of 0.463. Potential interactions between sulbactam pivoxil and common pharmaceutical excipients were evaluated by thermal analysis. The endothermic peak and the enthalpies of melting were preserved in almost all the analyzed mixtures. Conclusion: The powder was constituted by micro-sized crystals of sulbactam pivoxil that had suitable physicochemical properties for processing in controlled humidity environments. Thermal analyses suggested that sulbactam pivoxil is compatible with most of the evaluated excipients. The information obtained in the present study is relevant for the development, manufacturing, and storage of formulations that include sulbactam pivoxil.Fil: Gallo, Loreana Carolina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: González Vidal, Noelia Luján. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Ferreira, Fabio F.. Universidad Federal do Abc; BrasilFil: Ramírez Rigo, María Veronica. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

Synthesis and characterization of mesoporous SBA-15 and SBA-16 as carriers to improve albendazole dissolution rate

Albendazole (ABZ, anti-parasitic active pharmaceutical ingredient) is a crystalline low water-soluble drug, thus the dissolution rate in gastrointestinal fluids is limited. Consequently, the improvement of the water solubility and dissolution rate of ABZ implies a great challenge for a more efficient treatment of hydatidosis. In this context, SBA-15 and SBA-16 ordered mesoporous silica materials were synthetized and loaded with ABZ. X-ray diffraction, FT-IR spectroscopy, nitrogen physisorption manometry, particle size distribution and scanning electronic microscopy were used to characterize unloaded and loaded materials (ABZ/SBA-15 and ABZ/SBA-16). The loaded ABZ amount in the carriers was estimated by elemental analysis. For the loaded materials, the drug solubility and release profile were evaluated. In addition, mathematical models were compared to explain the dissolution kinetics of ABZ from mesoporous solids. ABZ was successfully loaded into the mesopores. The amorphous state of the adsorbed ABZ was confirmed by differential scanning calorimetry that resulted in a notable increment in the dissolution rate compared to crystalline ABZ. Drug release behaviors were well simulated by the Weibull model for ABZ/SBA-15 and by the Gompertz function for pure ABZ and ABZ/SBA-16. The SBA-15 carrier exhibited the highest drug loading and dissolution rate becoming a promising material to improve ABZ bioavailability.Fil: Adrover, María Esperanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Pedernera, Marisa Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Bonne, Magali. Université Haute-alsace.; Francia. Université de Strasbourg; FranciaFil: Lebeau, Bénédicte. Université Haute-alsace.; Francia. Université de Strasbourg; FranciaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Desing of 3D printed veterinary capsule devices for supplement administration

Urea is commonly employed in ruminant feed supplementation, however is rapidly hydrolyzed in the rumen. Therefore, modifying the urea release has become a pharmacotechnical challenge. In this work, a proof of concept study was developed to test the feasibility of using Fused Deposition Modeling-3D printing (3DP) to create veterinary capsule devices (CDs) that could allow the control of urea release. Three designs were assayed: D1 = one-compartment capsule with body and cover printed in polylactic acid (PLA), D2 = one-compartment capsule with body of PLA and cover of polyvinyl alcohol (PVA) and D3 = multi-compartment capsule with cover and body of PLA, the body presenting a PVA orifice in one extreme and five PVA partitions inside. The release of urea from the CDs was performed in 1 liter of distilled water, 40 ºC and 50 rpm. Two sinkers of differents weights and two types of paddles were evaluated. D1 showed no release of urea within 24 hours. D2 exhibited a retard release without influence of sinkers and paddles. D3 showed immediate and prolonged profiles, thus the release was affected by sinkers/paddles and some printing errors. These preliminary designs showed the possibility of using 3DP as a technological platform to modify the urea release in ruminant feed supplementation.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Peña, Juan Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Real, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Cotabarren, Ivana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina6ta Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2020+1)CordobaArgentinaUniversidad Nacional de CórdobaUniversidad Nacional de Rosari

A Review on Influence of Spray Drying Process Parameters on the Production of Medicinal Plant Powders

Medicinal plants are used by 80% of the world population as primary health care and the phytomedicine market is growing exponentially. Currently, the production of phytopharmaceuticals with proper efficacy, safety and consistent quality constitutes a relevant challenge. The dried dosage forms of medicinal plants are preferred than liquid presentations because of their higher stability. The spray drying technology is the most employed process to produce dried extracts from medicinal plant liquid extracts. These powders need to meet certain physicochemical (e.g., moisture content, hygroscopicity, particle size, density, the concentration of active ingredients) and mechanical (e.g., flowability and compressibility) properties to be used in a solid pharmaceutical form. In addition, high process yields and good powder quality can be obtained by selecting suitable process parameters: spray drying operating conditions and type/concentration of carriers (drying coadjuvants). The optimal process parameters are strongly affected by the chemical nature of the medicinal plant extract. This review aims to give a general guide to understand the effect of the process parameters on the product properties and process yield. This guideline could help practitioners and researchers to initially select the levels of the process variables to decrease the time and cost of the development stage of medicinal plants powders.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentin

3D printing of PVA capsular devices for modified drug delivery: design and in vitro dissolution studies

The fabrication through FDM 3D printing of hollow systems intended for oral drug delivery constitutes an attractive technology to change personalized medications in the compounding pharmacy. In this sense, this work studied the design and 3D printing of one compartment capsular devices filled of drugs that could require a delayed release mechanism. The optimization of printing parameters such as material flow rate and printing speed by means of simple gcode modifications, resulted critical to allow the production of PVA capsular devices in a single manufacturing process. In addition, the disintegration and dissolution studies of the obtained capsular device confirmed the existence of a delayed drug release compared to commercial hard-gelatin capsules. Furthermore, the use of sinkers in the dissolution tests resulted in similar dissolution profiles regardless the rotation speed. Finally, Gompertz and Weibull equations were the kinetic models that best fitted the experimental data corresponding to immediate release with lag time type profiles. Overall, this work provides insights to understand the effect of the printing parameters on the production of PVA capsular devices and suggests a simple design and single manufacturing process that can be adopted in the future compounding pharmacy.Fil: Cotabarren, Ivana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

Formulation and characterization of polysaccharide microparticles for pulmonary delivery of sodium cromoglycate

Sodium cromoglycate (SC) is an antiasthmatic and antiallergenic drug commonly used for chronic inhalation therapy, however many daily intakes are required due to the fast drug clearance from airways. For these reasons, SC polymeric particles for inhalatory administration with adequate aerosolization and mucoadhesive properties were designed to prolong the drug residence time in the site of action. Sodium carboxymethylcellulose (CMCNa), sodium hyaluronate and sodium alginate were selected to co-process SC by spray drying. The influence of these polysaccharides on the spray drying process and powder quality were evaluated (among others, morphology, size, moisture content, hygroscopicity, flowability, densities, liquid sorption and stability). In vitro aerosolization, drug release and mucoadhesion performance were also studied. Particularly, a novel method to comparatively evaluate the interaction between formulations and mucin solution (mucoadhesion test) was proposed as a rapid methodology to measure adhesion properties of inhalable particles, being the results as indicative of clearance probability. Among all the studied formulations, the powder based on SC and CMCNa exhibited the best mucoadhesion and aerosolization performance, the highest process yield and adequate moisture content, hygroscopicity and stability. SC-CMCNa formulation arose as a promising inhalatory system to reduce the daily intakes and to increase the patient compliance.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Ramírez Rigo, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

Development of porous spray-dried inhalable particles using an organic solvent-free technique

A simple technique to produce spray-dried porous particles for inhalatory administration was developed. The particles were produced using water as solvent, Sodium Cromoglycate as model drug and ammonium bicarbonate as pore forming agent. A central composite design was employed to study the influence of the: pore-forming agent concentration (in the drug aqueous solution fed to the spray dryer) and air inlet temperature on: process yield and powder properties. The powder particle size distribution, moisture content, densities and estimated aerodynamic diameters were studied. Also, particles morphology, hygroscopicity, surface area, in vitro aerosolization properties, dissolution rate and stability were evaluated for some selected samples. In addition, a novel friability test was proposed for mechanical resistance evaluation of the porous materials. A pore forming agent concentration of 1.25% (w/w) and an air inlet temperature of 170 °C were the optimal process parameters to produce porous particles suitable for inhalatory administration. The process yield was high and it was demonstrated that the particles were free of ammonium bicarbonate. The porous powder, obtained by a simple and scalable technique, exhibited low tap density, good stability even at long storage periods (12 months), appropriate mechanical resistance, high initial dissolution rate and excellent aerosolization performance.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Ramírez Rigo, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentin

Herbal medicine: Dry extracts production and applications

Medicinal plants have provided therapeutic agents for thousands of years and continue being a great source of novel pharmaceutical products. Two-thirds of the world population still relies to some extent on natural medicines for primary health care. In addition, the demand for medicinal plant products is now increasing in both developing and developed countries as a consequence of a growing aging population and increasing consumer awareness about general health. Nevertheless, there is a widespread concern regarding safety, efficacy and quality of herbal medicines. Currently, many countries are conscious about the need of regulatory guidelines for medicinal herbs formulation, production and use. Phytomedicines represent a wide range of product types: from raw herbs (dried or fresh) to others with different processing degrees (such as tinctures and extracts). The production of herbal medicines involves adequate cultivation and post-harvest methodologies as well as botanical identification of the vegetable drugs. For herbal medicine end-products with added value, appropriate extraction procedures (i.e., in terms of bioactivity), standardization of extracts, selection and tuning of the drying processes operating conditions and design of pharmaceutical formulations are also necessary. In this chapter the current global scenario of phytomedicine is first presented, evaluating its impact on public health and markets. The challenges associated to safety, efficacy and quality of herbal medicines due to the extracts complexity are then introduced. Understanding the great importance of providing accurate dosages of herbal therapeutic agents, the production of dry plant extracts is next discussed focusing on: the drying step including the formulation of the solution to be dried (which comprises the herbal extract) and the dried extract quality. Regarding the available technologies for preparing dry medicinal plants extracts, spray drying is particularly described. This technique is the most commonly used in the herbal processing industry due to its ability to generate particulate products with precise specifications in continuous operations. Several key studies about the effect of the operating conditions and feed composition on the yield of the spray drying process and the particles properties are subsequently summarized. For the production of tablets by direct compression, stable herbal dried powders with good flow properties are required. Consequently, the effects of different processing variables on the stability and flowability of dried extracts are also presented. The formulation of solid dosage forms, based on spray-dried plant extracts, for conventional and modulated delivery is then reviewed. Besides, existing strategies to modulate the drug delivery of plant extracts are also described. Since modified-release phytomedicines are still in an exploratory stage, the prospective for the development of novel products is finally discussed.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Ramírez Rigo, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Piña, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentin

A comparative study of spray-dried medicinal plant aqueous extracts: Drying performance and product quality

In the manufacture of herbal medicinal tablets, dried plant extracts are employed as the therapeutic ingredient. These powders, usually obtained by spray drying, are typically hygroscopic and possess poor flow and compactability for the manufacture of tablets by direct compression (DC). Besides, spray-drying operating conditions and liquid feed composition are reported to be dependent on the herbal medicine. Consequently, the production of dried extractsimplies long new product development times. Therefore, the goal of this paper was to: a) provide recommendations as initial production point of herbal powders suitable for DC by spray drying and b) study the powder properties to identify those that are affected by the extract nature. Particularly, a unique set of operating conditions was found to be appropriate to produce powders of seven different medicinal plant extracts. In fact, all the spray-dried products showed adequate flowability, stability and compactability.Powders properties, as particle size and morphology, moisture content, hygroscopicity, flowability and compact hardness were not a function of the type of herb. Conversely, the process yields and glass transition temperature, particle and bulk densities, powder composition, compact porosity, wetting and disintegration times were found to be dependent on the chemical nature of the herbs.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Ramírez Rigo, María Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Piña, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bucala, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin

Influence of microbubbles on the production of spray-dried inhalable particles

The aim of this work was to study the effect of gas microbubbles on the production of particles suitable for inhalatory administration by a spray drying technology. An antiasthmatic model drug (sodium cromoglycate) was selected in order to evaluate the effect of different gases (air, CO2 and N2) and spray drying operating conditions on the particles aerosolization performance. To this end, gas supersaturated aqueous drug solutions were obtained in a pressurized vessel and then processed by spray drying. The process yield, morphology, size, bulk and tap densities, moisture content and aerosolization properties of the particles were evaluated. The presence of microbubbles in the spray drying feed led to powders with smaller mean geometric sizes than particles obtained without bubbles. The gas-water solubility emerged as a key parameter to obtain inhalatory particles with good aerosolization properties. High water-soluble gases led to bigger particles, while low soluble ones allow to produce smaller particles. The use of air (with an intermediate water solubility respect to CO2 and N2) and an adequate set of spray drying operating conditions allowed to obtain sodium cromoglycate particles with superior aerosolization properties than a commercial formulation. Overall, a novel, simple and low-cost method to produce inhalatory particles with excellent aerosolization properties was developed by supersaturating the spray drying liquid feed without using pore-forming agents during the production step, or carriers in the final formulation.Fil: Gallo, Loreana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Serain, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Renaudo, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Química; ArgentinaFil: Lopez, Eduardo. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Bucalá, Verónica. Universidad Nacional del Sur. Departamento de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin