Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

Current Problems Involving the Dismantle of Asbestos- Cement Sheets in Buildings. The Case of Central Market in Alicante

The project and the works described in this article mainly deal with the removal of the current asbestos-cement covering of the roof of the Central Market in Alicante and its replacement with zinc diamond-shaped scales, similar to the originals which were implemented in 1921 when the building was put into service. These upgrades were necessary to avoid the causes (and consequences) of rainwater infiltration, as described in an earlier report in 2006, also drafted by the author of this article. The article illustrates the difficulties involving the practical application of Spanish Code RD 396/2006 (minimum safety and health requirements for work with risk of exposure to asbestos) in a complex case such as this, especially with regard to aspects such as economic (increasing costs), technical (increased difficulty of implementation), and the total duration of the work (total increase in duration due to interference with other trades).

Saberes expertos en la encrucijada: Razas, anti/racismo y ciencias en la UNESCO 1949-1950

El presente artículo se propone estudiar, retomando diversos aspectos del Análisis Materialista del Discurso, una serie de discusiones de la inmediata posguerra que colocaron la cuestión racial y al racismo en el centro de la agenda de las ciencias (naturales y sociales) así como de los organismos internacionales. Antes que reponer y reproducir una imagen de coherencia u homogeneidad en estos debates, propondremos una lectura a contrapelo capaz de mostrar la articulación contingente de elementos de diversa procedencia, las contradicciones, las tensiones y, sobre todo, las luchas involucradas en ellos.En un primer apartado presentaremos algunos aspectos generales de las discusiones en torno de la cuestión racial en la Segunda Posguerra y el papel que en ello tendrían UNESCO y las ciencias sociales. Luego, nos referiremos sintéticamente a los debates fascistas en torno de la cuestión racial para, en el siguiente apartado, desarrollar la primera de nuestras tesis: la existencia de una relación de diálogo/antagonismo entre la declaración de 1949 de UNESCO y los debates fascistas en torno de las leyes raciales entre 1935 y 1938. A partir de ello, en la sección siguiente, desplegaremos nuestra segunda hipótesis, derivada de la primera: las discusiones de UNESCO además de dirigirse a un público general resultan de una disputa al interior de diversos campos científicos. En este tramo, analizaremos los vínculos entre ciencia y política que recorren los diversos documentos que conforman nuestro estudio. Finalmente, propondremos algunas reflexiones a modo de cierre.