Effect of lactose solid-state on the aerosolization performance of drug-carrier mixtures

Lactose, in particular α-lactose monohydrate, is the most used carrier for inhalation. Its surface and solid-state properties are of paramount importance in determining drug aerosolization performance. However, these properties may be altered by processing, such as micronization, thus affecting the product performance and stability. The present research project focused on the study of the effect of lactose solid-state on the aerosolization performance of drug-carrier mixtures, giving particular attention to the impact of micronization on lactose physico-chemical properties. The formation of a fraction of hygroscopic anhydrous α-lactose, rather than amorphous lactose, as a consequence of the mechanical stress stemming from micronization was evidenced by 1H NMR, XRPD and DSC analyses performed on samples of micronized lactose. The development of a new DVS method capable to identify and quantify different forms of α-lactose (hygroscopic anhydrous, stable anhydrous and amorphous), even simultaneously present in the same sample, confirmed the results obtained with the above-mentioned techniques. The influence of lactose solid-state on drug respirability was then evaluated through the preparation and in vitro aerodynamic assessment of ternary and binary mixtures containing two different drugs. In particular, the use, as carriers, of anhydrous forms of α-lactose in place of the conventional α-lactose monohydrate resulted in significantly improved respirability in the case of salbutamol sulphate and poorer performance in the case of budesonide. In an attempt to rationalize the obtained results, IGC was selected as a tool to investigate possible variations in the surface energy of the studied lactose carriers and APIs. A direct correlation between the total surface free energy of lactose carriers and drug respirability was not found. However, salbutamol sulphate and budesonide exhibited different specific surface free energy, to which the difference in the aerosolization performance may be, at least in part, ascribed.

Clasificación y caracterización de zonas húmedas del litoral alicantino (SE España), mediante las metodologías CAR/ASP y MEDWET: estudio de caso del Saladar de Aguamarga y el Fondet de La Senieta

En este estudio se pretende caracterizar las comunidades vegetales presentes en ambientes litorales en el SE de la provincia de Alicante, mediante el cartografiado de zonas homogéneas de vegetación, mediante el empleo de los catálogos propuestos por el RAC-SPA y Medwet. De este modo, se han determinado 7 unidades ambientales en cada uno de los sectores analizados en el estudio (saladar de Urbanova y el Fondet de la Senieta), pudiendo comparar las diferencias entre ambas técnicas. Así, se seleccionaron 10 parcelas al azar y su vegetación fue muestreada según la metodología, basada en transectos, denominada «quadrat technique» y se identificaron las diferentes especies vegetales en el campo. Por otro lado, la medida de la cobertura vegetal total también fue tomada según la metodología de «Braun Blanquet». Se han empleado los programas informáticos CartaLinx® y ArcView® para el cartografiado de las unidades vegetales. Así, trabajo se pretende proporcionar herramientas técnicas y garantizar la gestión sostenible de los humedales y sus recursos naturales.

Enantioselective catalytic lithiation using a chiral binaphthyl derivative as electron carrier

The lithiation, of the secondary chloride 2, catalyzed by binaphthyl derivatives, i.e. BINAM 4, BINOL 5, BINAP 6, H8-BINAP 7, Tol-BINAP 8, 2,2’-bis(pyrrolidin-1-yl)-1,1’-binaphthalene 9, and 2,2’-dimethyl-1,1’-binaphthalene 11, in the presence of different ketones has been studied, yielding the corresponding alcohol derivatives 3 and 12-16 in moderate to good yields. Binaphthyl derivative 11 has revealed to be very active as catalyst in the lithiation process at room temperature, and has allowed the preparation of the alcohol derivatives with enantioselectivities up to 50%.