Quality-by-design driven approach in the formulation of an anti-ulcer and gastro-protective oral suspension.

OBJECTIVE: This work aims to present a Quality-by-Design (QbD) step-by-step methodology to formulate anti-ulcer and gastro-protective oral suspensions. METHODS: Sucralfate was used as a drug model. The Quality Target Product Profile was established early during preformulation. Viscosity, resuspendability, pH, and density were assessed through the screening of several suspension platforms based on different prototype compositions. A compatibility study between the active pharmaceutical ingredient and the excipients was performed by thermal analysis and infrared spectroscopy. An Ishikawa fishbone diagram and Failure Mode and Effect Analysis were employed to identify the Critical Material Attributes (CMAs), Critical Process Parameters (CPPs), and Critical Quality Attributes (CQAs). CMAs' and CPPs' impact on identified CQAs was further assessed through a 22 full factorial experimental design at normal conditions after manufacture and one month at super-accelerated stress conditions. Results: The lead prototype exhibited no physicochemical incompatibilities. The risk assessment tools revealed that the concentration of the wetting agent and the total concentration of thickening agents represented critical factors for the quality profile of the preparation in terms of viscosity. The optimized formulation comprising 1.125 w/v% total concentration of Natrosol 250 HX and Avicel RC 591 exhibited an enhanced performance according to the established profile. CONCLUSIONS: The analytical and physicochemical tests showed the robustness and compliance of the final preparation with the quality profile. The proposed step-by-step methodology based on QbD, Design of Experiments, and Quality Risk Management presented in our research holds practical implications for local industries and formulation scientists involved in the development of oral suspensions.

Influence of polyamide composite casings with silver-zinc crystals on the quality of beef and chicken sausages during their storage.

The influence of polyamide 6 composite casings with silver-zinc crystals powder on some of the physicochemicalphysical-chemical, microbiological and sensory indicators of beef and chicken sausages during their storage was evaluated. Beef and chicken sausages were elaborated by using the conventional technology for sausage meat thin pasta; in each case, it was maintained a control batch to compare changes during the storage (4 and 12 °C, 75%-85% RH). To estimate the shelf life was considered sensory evaluation as a criterion for rejection. The results were processed as failure incomplete data via the Weibull distribution and it was admitted 5% of deteriorated units. It did not find a significant effect (p ≤ 0.05) due to the addition of silver-zinc crystals on the values of pH, aw, color, texture and sensory attributes of sausages, but did influence TBARS results, with lower values compared to control products. It reduced the counts of aerobic mesophilic microorganisms and lactic acid bacteria during the storage. The shelf life of chicken sausage was not affected at any storage temperature; while for the beef sausage stored at 4 °C, its shelf life increased in 9 days, although at 12 °C did not exist difference among treatments.

Topical Chitosan-Based Thermo-Responsive Scaffold Provides Dexketoprofen Trometamol Controlled Release for 24 h Use.

Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improving patient compliance. Concerning that, this work aims to develop a suitable chitosan-based thermo-responsive scaffold to provide 24 h controlled release of Dexketoprofen trometamol (DKT). Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and FT-IR. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C, and the profiles were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 h (77.75 ± 2.72%) and reduced the burst release in the initial 6 h (40.18 ± 1.00%). The formulation exhibited a lower critical solution temperature (LCST) at 34.96 °C, and due to this phase transition, an increased release was observed at 38 °C (88.52 ± 2.07% at 12 h). The release profile for this formulation fits with Hixson-Crowell and Korsmeyer-Peppas kinetic models at both temperatures. Therefore, the developed scaffold for DKT delivery performs adequate controlled release, thereby; it can potentially overcome adherence issues and complications in wound healing applications.

Persea Americana Agro-Industrial Waste Biorefinery for Sustainable High-Value-Added Products.

Significant problems have arisen in recent years, such as global warming and hunger. These complications are related to the depletion and exploitation of natural resources, as well as environmental pollution. In this context, bioprocesses and biorefinery can be used to manage agro-industrial wastes for obtaining high-value-added products. A large number of by-products are composed of lignin and cellulose, having the potential to be exploited sustainably for chemical and biological conversion. The biorefinery of agro-industrial wastes has applications in many fields, such as pharmaceuticals, medicine, material engineering, and environmental remediation. A comprehensive approach has been developed toward the agro-industrial management of avocado (Persea americana) biomass waste, which can be transformed into high-value-added products to mitigate global warming, save non-renewable energy, and contribute to health and science. Therefore, this work presents a comprehensive review on avocado fruit waste biorefinery and its possible applications as biofuel, as drugs, as bioplastics, in the environmental field, and in emerging nanotechnological opportunities for economic and scientific growth.

Exploration of Bioengineered Scaffolds Composed of Thermo-Responsive Polymers for Drug Delivery in Wound Healing.

Innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan, polyvinylpyrrolidone, alginate, and poly(ε-caprolactone) can be used to create biocompatible and biodegradable scaffolds. These processed thermo-responsive biomaterials possess 3D architectures similar to human structures, providing physical support for cell growth and tissue regeneration. Furthermore, these structures are used as novel drug delivery systems. Locally heated tumors above the polymer lower the critical solution temperature and can induce its conversion into a hydrophobic form by an entropy-driven process, enhancing drug release. When the thermal stimulus is gone, drug release is reduced due to the swelling of the material. As a result, these systems can contribute to the wound healing process in accelerating tissue healing, avoiding large scar tissue, regulating the inflammatory response, and protecting from bacterial infections. This paper integrates the relevant reported contributions of bioengineered scaffolds composed of smart thermo-responsive polymers for drug delivery applications in wound healing. Therefore, we present a comprehensive review that aims to demonstrate these systems' capacity to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to patient convenience and reduce drug toxicity and side effects.

Biosensors for the Detection of Bacterial and Viral Clinical Pathogens.

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living through due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors' design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care.

Green Synthesis of Gold and Silver Nanoparticles from Plant Extracts and Their Possible Applications as Antimicrobial Agents in the Agricultural Area.

Currently, metal nanoparticles have varied uses for different medical, pharmaceutical, and agricultural applications. Nanobiotechnology, combined with green chemistry, has great potential for the development of novel and necessary products that benefit human health, environment, and industries. Green chemistry has an important role due to its contribution to unconventional synthesis methods of gold and silver nanoparticles from plant extracts, which have exhibited antimicrobial potential, among other outstanding properties. Biodiversity-rich countries need to collect and convert knowledge from biological resources into processes, compounds, methods, and tools, which need to be achieved along with sustainable use and exploitation of biological diversity. Therefore, this paper describes the relevant reported green synthesis of gold and silver nanoparticles from plant extracts and their capacity as antimicrobial agents within the agricultural field for fighting against bacterial and fungal pathogens that can cause plant, waterborne, and foodborne diseases. Moreover, this work makes a brief review of nanoparticles' contribution to water treatment and the development of "environmentally-friendly" nanofertilizers, nanopesticides, and nanoherbicides, as well as presenting the harmful effects of nanoparticles accumulation in plants and soils.

Electrospun nanofibers: A nanotechnological approach for drug delivery and dissolution optimization in poorly water-soluble drugs.

Electrospinning is a novel and sophisticated technique for the production of nanofibers with high surface area, extreme porous structure, small pore size, and surface morphologies that make them suitable for biomedical and bioengineering applications, which can provide solutions to current drug delivery issues of poorly water-soluble drugs. Electrospun nanofibers can be obtained through different methods asides from the conventional one, such as coaxial, multi-jet, side by side, emulsion, and melt electrospinning. In general, the application of an electric potential to a polymer solution causes a charged liquid jet that moves downfield to an oppositely charged collector, where the nanofibers are deposited. Plenty of polymers that differ in their origin, degradation character and water affinity are used during the process. Physicochemical properties of the drug, polymer(s), and solvent systems need to be addressed to guarantee successful manufacturing. Therefore, this review summarizes the recent progress in electrospun nanofibers for their use as a nanotechnological tool for dissolution optimization and drug delivery systems for poorly water-soluble drugs.

Development of immediate release Rupatadine fumarate 10 mg tablets: A Quality by Design (QbD) approach.

Objective: The main objective of this research is to develop an immediate release Rupatadine fumarate 10 mg tablets formulation by direct compression, through a Quality by Design approach in Costa Rica. Methods: According to a Quality by Design approach; Target Product Profile, Quality Target Product Profile, and the Critical Quality Attributes were defined. In the preformulation study, compatibility tests were carried out between the raw materials. The Critical Material Attributes were established using Quality Risk Management. Three formulation prototypes were prepared by direct compression and its Critical Process Parameters were defined. The analysis of the prototypes was realized in terms of organoleptic properties, identification, potency, content uniformity, dissolution, disintegration, friability and loss by drying. Results: All the prototypes showed a white or slightly pink surface, potency between 90.0 -110.0 % of the labeling, an acceptance value for the content uniformity lower than the specification (AV < 15), the dissolved amount of active pharmaceutical ingredient was greater than 85.0 % at 30 minutes, friability less than 1.0 %, a disintegration time less than 15 minutes and moisture content less than 2.0 %. Conclusions: The approaching of a Quality by Design model to the current development allowed to obtain satisfactory results in the three formulation prototypes. The excipients to be used can be lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, pregelatinized starch, magnesium stearate, stearic acid, and PVP K-30.

Do subtoxic levels of chlorate influence the desiccation tolerance of Egeria densa?

Among the different factors hypothesized to be responsible for the virtual disappearance of Egeria densa, once a dominant aquatic macrophyte in a southern Chile wetland ecosystem, are the negative effects of certain chemical compounds (mainly chlorate) and harsh environmental conditions (desiccation caused by prolonged atmospheric exposure). The authors performed an integrated experiment in which E. densa plants were first exposed for four weeks inside a mesocosm system to levels of chlorate that existed in the wetland at the time of the plant's demise and then exposed to desiccation conditions that also resembled those that the system had experienced. Hence, the authors tested the hypothesis that E. densa plants exposed to sublethal levels of chlorate are more susceptible to the deleterious effect of desiccation compared with plants that had not been exposed to chlorate. This hypothesis was tested by means of quantifying physiologically related parameters in plants right after the four weeks under water and then after the desiccation period of 6 h. Their results rejected this hypothesis, because all plants, regardless of their history, are equally affected by desiccation.

Salmon aquaculture and antimicrobial resistance in the marine environment.

Antimicrobials used in salmon aquaculture pass into the marine environment. This could have negative impacts on marine environmental biodiversity, and on terrestrial animal and human health as a result of selection for bacteria containing antimicrobial resistance genes. We therefore measured the numbers of culturable bacteria and antimicrobial-resistant bacteria in marine sediments in the Calbuco Archipelago, Chile, over 12-month period at a salmon aquaculture site approximately 20 m from a salmon farm and at a control site 8 km distant without observable aquaculture activities. Three antimicrobials extensively used in Chilean salmon aquaculture (oxytetracycline, oxolinic acid, and florfenicol) were studied. Although none of these antimicrobials was detected in sediments from either site, traces of flumequine, a fluoroquinolone antimicrobial also widely used in Chile, were present in sediments from both sites during this period. There were significant increases in bacterial numbers and antimicrobial-resistant fractions to oxytetracycline, oxolinic acid, and florfenicol in sediments from the aquaculture site compared to those from the control site. Interestingly, there were similar numbers of presumably plasmid-mediated resistance genes for oxytetracycline, oxolinic acid and florfenicol in unselected marine bacteria isolated from both aquaculture and control sites. These preliminary findings in one location may suggest that the current use of large amounts of antimicrobials in Chilean aquaculture has the potential to select for antimicrobial-resistant bacteria in marine sediments.

Influencia del empaque y envasado sobre las propiedades fisicoquímicas del hongo comestible Pleurotus ostreatus / Influences of the packing and packed about physiochemical properties of edible mushroom Pleurotus ostreatus

Objetivo. Evaluar la influencia de diferentes empaques y atmósferas sobre las propiedades fisicoquímicas del hongo comestible Pleurotus ostreatus. Materiales y métodos. Los hongos fueron almacenados durante 15 días a 4ºC, utilizando tres empaques: 1) espuma de poliestireno con película de recubrimiento de polivinil cloruro (empaque comercial), 2) Polietilentereftalato con películas de recubrimiento de polipropileno biorientado y 3) polietileno de baja densidad y tres atmósferas de envasado: 1) Aire, 2) 100% N2 y 3) 10% O2, 10% CO2 y 80% N2. Después de almacenados se derminaron los posibles cambios de las variables fisicoquímicas (pH, acidez, °Brix, humedad, cloruros, color y textura) Resultados. Las muestras presentaron diferencias estadísticas en los parámetros fisicoquímicos del hongo fresco por efecto de los factores tiempo, empaque y atmósfera. Los rangos de variación se consideraron aceptables debido a las características propias del producto, como ente biológico que continua con sus procesos metabólicos. Los cambios de color en las condiciones de control (Grupo 1: Empacado Comercial y Grupo 1: Atmósfera Aire) no fueron muy acentuados, siendo instrumentalmente más apreciable, sin llegar a serlo para el observador. La textura en todos los casos presentó una disminución en la resistencia mecánica, debido a los posibles procesos fermentativos y al deterioro por la alta tasa metabólica. Conclusiones. Los resultados permiten identificar que no hubo un efecto apreciable del empaque y de las atmósferas modificadas en las propiedades fisicoquímicas del hongo Pleurotus ostreatus, lo que hace que el empaque comercial sea más práctico por efecto de costos de producción.

GRAZING ON GIANT KELP MICROSCOPIC PHASES AND THE RECRUITMENT SUCCESS OF ANNUAL POPULATIONS OF MACROCYSTIS PYRIFERA (LAMINARIALES, PHAEOPHYTA) IN SOUTHERN CHILE(1).

The giant kelp Macrocystis pyrifera (L.) C. Agardh is widely distributed in the Northern Hemisphere and Southern Hemisphere, yet it exhibits distinct population dynamics at local to regional spatial scales. Giant kelp populations are typically perennial with the potential for year-round reproduction and recruitment. In southern Chile, however, annual giant kelp populations exist and often persist entirely on secondary substrata (e.g., shells of the slipper limpet Crepipatella fecunda [Gastropoda, Calyptraeidae]) that can cover up to 90% of the rocky bottom. In these populations, the macroscopic sporophyte phase disappears annually during winter and early spring, leaving a 3-4 month period in which a persistent microscopic phase remains to support the subsequent year's recruitment. We tested the effects of a suite of grazers on the recruitment success of this critical microscopic phase at two sites in southern Chile. Field experiments indicated that the snail Tegula atra negatively impacted M. pyrifera sporophyte recruitment, but that recruitment was highest in the presence of sessile female limpets, C. fecunda. Conversely, small male C. fecunda (biofilm grazers) did not regulate kelp recruitment. Laboratory observations showed that C. fecunda males only grazed on microscopic kelp gametophytes and small (<250 µm) sporophytes, rejecting larger sporophytes, whereas T. atra grazed on all the kelp stages. Recruitment to the C. fecunda treatments far exceeded that to bare rock in the absence of grazers but was not due to the physical presence of C. fecunda shells. We concluded that the key to M. pyrifera recruitment success in southern Chile is its capacity to colonize secondary substrates provided by the slipper limpet C. fecunda.

Algunas consideraciones sobre el virus de la hepatitis C / Some considerations about hepatitis C virus

A pesar de los grandes logros alcanzados en el comportamiento de la infección por el virus de la hepatitis C, existe todavía gran desinformación en relación a la epidemiología, el diagnóstico y los esquemas terapéuticos dirigidos a combatir el proceso infeccioso que éste causa. La presente revisión bibliográfica pretende describir los aspectos más relevantes del comportamiento de dicho virus y la forma de abordaje y manejo del mismo

Infección tuberculosa en contactos de pacientes positivos y negativos al VIH con tuberculosis : resultados preliminares / Tuberculosis infection (TB) in household contacts of patients HIV-positive and HIV-negative with TB

Los datos disponibles sobre el grado de infectividad de las personas positivas al virus de inmunodeficiencia humana (VIH) con tuberculosis (TB) son controversiales. El presente estudio determina el grado de infectividad tuberculosa de los individuos positivos al VIH con TB activa entre sus convivientes. Los contactos convivientes de sujetos VIH positivos con TB y de sujetos VIH negativos con TB son tamizados para la infección tuberculosa y la enfermedad activa en sus residencias en una visita inicial y varias de seguimiento, mediante la prueba de tuberculina, exámen físico, historia clínica y procedimientos radiográficos. En la visita inicial, punto de corte del presente análisis, la reactividad al derivado protéico purificado (PPD) (Induración, mayor o igual que, 10mm) ha mostrado ser menor en los contactos de individuos positivos al VIH (41/84 [46.6//] que en aquellos de individuos negativos al VIH (118/195 [61.8//] (RR=0.72, IC 95//:0.57, 0.92). Entre los convivientes, menor o igual a, 15 años, la reactividad al PPD ha mostrado ser también menor en aquellos de sujetos VIH-positivos (21/46 [45.7//]) que en los de sujetos VIH negativos (40/70 [57.1//]) (RR=0.80, IC 95//:0.55, 1.16). Esta diferencia persiste luego de evaluar aquellos contactos, mayores o igual a 15 años que no mostraron anergia. Estos resultados tienden a sugerir un menor grado de transmisibilidad tuberculosa en pacientes con TB positivos al VIH que en aquellos negativos al VIH. Las visitas de seguimiento arrojarán una respuesta definitiva sobre dicha hipótesis

Pseudohipoparatiroidismo y cardiomiopatía hipocalcémica / Pseudohypoparathyroidism an hypocalcemic myocardiopathy

Se presenta un caso de pseudohipoparatiroidismo complicado con una cardiomiopatía hipocalcémica y un síndrome convulsivo. En el momento del diagnóstico, los hechos más destacados fueron: rasgos fenotípicos característicos, cardiomegalia radiológica, alteraciones electrocardiográficas compatibles con hipocalcemia, osteoporosis generalizada y calcificaciones de tejidos blandos en la radiografía de esqueleto, calcio plasmático 4,53 mg% y fosfato plasmático 7,7mg%. En respuesta al tratamiento con vitamina D3, gluconato de calcio, hidróxido de aluminio, acetildigitoxina, hidroclorotiazida, y con un régimen pobre en fosfatos, se obtuvo una mejoría progresiva del calcio y fósforo plamáticos, junto con la normalización de la silueta cardíaca y del trazado electrocardiográfico