Health risk assessment and quality reference values of potentially toxic elements in soils of the Southwestern Amazonas State - Brazil.

The geochemical processes involved in the Amazon soils formation are not totally understood because its geological and pedological features were formed during different geological events and different times. The Southwestern region of Amazonas State is an example of a region where the soils were developed from rocks formed by sedimentary processes and, nowadays, the soils continue receiving seasonal inputs from the Andes sediments. Data on geochemical patterns of this region are scarce, and there is no information about the possible effects of the natural or unnatural enrichment of potentially toxic elements (PTEs). Thus, this study represents the first research into the geochemical patterns of PTEs in soils of Southwestern Amazonas State. Further, we carried out a human health risk assessment and a proposal for Quality Reference Values (QRV) for thirteen PTEs (As, Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Ti, V, Zn and Zr). Our findings showed that the PTEs contents in soil samples collected in the lowland areas are strongly influenced by sediments inputs, while samples localized in the highland areas are weakly influenced by sediments inputs and present depletion of PTEs. Barium, Cr, Cu, Ni and Pb were the PTEs most influenced by sediment's deposition. The soil contamination assessment showed the existence of enrichment of the potentially toxic elements in soil samples, which may be a consequence of the natural inputs of the Andean sediments. Furthermore, Co and Cr exceed the safety zone for carcinogenic risk assessment, which indicates the need to monitor these elements and their possible effects on the health of the population in this region.

Evaluation of physicochemical properties and dissolution studies on quality control of low water solubility drugs (raw materials and pharmaceutical formulations) / Evaluación de propiedades fisicoquímicas y estudios de disolución sobre el control de calidad de fármacos de baja solubilidad en agua (materias primas y formulaciones farmacéuticas)

SUMMARY The purpose of this study was to evaluate physicochemical properties and dissolution studies of furosemide (FUR), hydrochlorothiazide (HCTZ) and nifedipine (NIF), low water solubility drugs, in raw materials and pharmaceutical formulations. Surface and physicochemical characterization techniques -scanning electronic microscopy (SEM), thermogravimetry (TG), X-ray diffraction (XRD) and infrared (IR) spectrometry- as well as physical and physicochemical tests on tablets and capsules were applied as supporting information on drug quality control. Simple, rapid, and efficient UV-Vis methods were developed and validated for the determination of FUR, HCTZ and NIF samples. SEM exhibited considerable differences in the crystal morphological structures. Among the drugs studied, except for furosemide, more than one polymorph was present in the samples. Drug release profiles were satisfactory for all products. FUR and HCTZ tablets exhibited similar dissolution profiles, with very rapid release to the pharmaceutical specialties (reference, similar and generic). For HCTZ tablets, the similar drug (f2= 48.74) is not equivalent to the reference drug. NIF capsules (reference and compounded) showed a release >80% of stated on product labels, in 10 minutes. The results obtained in this study suggest that the quality parameters and drug dissolution profiles may have been influenced by the morphology and size of the crystals, excipients, and technological processes.

RESUMEN El propósito de este estudio fue evaluar las propiedades fisicoquímicas y los estudios de disolución de furosemida (FUR), hidroclorotiazida (HCTZ) y nifedipina (NIF), medicamentos de baja solubilidad en agua, en materias primas y formulaciones farmacéuticas. Técnicas de caracterización fisicoquímica y de superficie: microscopía electrónica de barrido (SEM), termogravimetría (TG), difracción de rayos X (XRD) y espectrometría infrarroja (IR), así como pruebas físicas y fisicoquímicas en tabletas y cápsulas que se aplicaron como información de apoyo sobre el control de calidad. Se desarrollaron y validaron métodos simples, rápidos y eficientes de UV-Vis para la determinación de muestras de FUR, HCTZ y NIF. SEM exhibió diferencias considerables en las estructuras morfológicas de cristal. Entre las drogas estudiadas, a excepción de la furosemida, más de un polimorfo estaba presente en las muestras. Los perfiles de liberación de fármacos fueron satisfactorios para todos los productos. Las tabletas FUR y HCTZ exhibieron perfiles de disolución similares, con una liberación muy rápida a las especialidades farmacéuticas (referencia, similares y genéricas). Para las tabletas de HCTZ, el medicamento similar (f2= 48,74) no es equivalente al medicamento de referencia. Las cápsulas NIF (de referencia y compuestas) mostraron una liberación >80% de la indicada en las etiquetas del producto, en 10 minutos. Los resultados obtenidos en este estudio sugieren que los parámetros de calidad y los perfiles de disolución del fármaco pueden haber sido influenciados por la morfología y el tamaño de los cristales, excipientes y procesos tecnológicos.