Amorphous dispersions of the Biclotymol antiseptic are obtained in polyvinylpyrrolidone (PVP), for different drug loadings, by co-milling at temperature below the glass transition of both components. Characterization of the dispersions by scanning differential calorimetry and temperature-dependent broadband dielectric spectroscopy shows them to be homogeneous amorphous molecular mixtures. A single glass transition with pronounced enthalpy recovery peak is observed, indicative of the formation of a homogeneous glass state characterized by substantial ageing. The polymer has a considerable antiplasticizing effect on the drug, increasing its glass transition temperature (T g) to well above room temperature. The T g of the mixture increases linearly with the macromolecular mass fraction. Three (macro)molecular relaxations are identified in the isothermal dielectric spectra of the mixtures. The slowest process corresponds to the cooperative (α relaxation) dynamics of the polymer chains and drug molecules simultaneously, and its relaxation time becomes longer the higher the polymer content. The fastest one is an intramolecular relaxation mode of Biclotymol, and is virtually unaffected by the presence of the polymer. Finally, the intermediate relaxation, which is also observed in pure PVP, is assigned to the motion of the polymer side groups. Its activation barrier increases with increasing drug content, indicative of a direct interaction of the drug with the pyrrolidone moieties, likely via hydrogen bonding to the carbonyl oxygen. Contrary to pure PVP, the mixtures are not hygroscopic. Mechanical amorphization by cryomilling yields thus glassy molecular mixtures at arbitrary drug concentration, with enhanced physical stability against crystallization and enhanced chemical stability against hydrolysis reactions.

This article analyses the arguments posed by Spanish jurists regarding the character and value in international nineteenth-century order of the titles to territories that the Spanish State inherited from the Catholic Monarchs. Focused on defending colonial interests in the Pacific, Spanish jurists insisted upon reproducing the legitimising arguments of the Conquest throughout the nineteenth century, until the German occupation of the Caroline Islands, expressly supported by the agreements reached at the Berlin Conference, forced them to rethink the foundations of their argument. The conflict surrounding the Caroline Islands was the first example of confrontation between articles 33 and 34 of the Act of Berlin and historical titles.

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