Hydration and dehydration induced changes in porosity of starch microspheres.

Characterization and tuning of the porosity of amorphous starch materials are important for many applications, including controlled release of encapsulated proteins. The porosities of these materials in dry and hydrated states can have different physicochemical origins and properties. Here, porosities of dry cross-linked starch microspheres and their hydration-induced transformations were characterized by small angle X-ray scattering, scanning electron and optical microscopies, thermogravimetric analysis, sorption calorimetry, nitrogen sorption, and helium-pycnometry. The analyses revealed that dry microspheres consist of porous cores with pore diameters below 100 nm and shells which appeared to be denser but contained wider pores (100-300 nm). The outer crust of the microspheres shell is non-porous, which restricts diffusion of nitrogen, water, and ethanol. Partial hydration triggered an irreversible collapse of dry porosity at 12 wt% water. Further hydration resulted in interfacial changes and promoted wet porosity, related to characteristic distances between polymer chains.

In silico solid state perturbation for solubility improvement.

Solubility is a frequently recurring issue within pharmaceutical industry, and new methods to proactively resolve this are of fundamental importance. Here, a novel methodology is reported for intrinsic solubility improvement, using in silico prediction of crystal structures, by perturbing key interactions in the crystalline solid state. The methodology was evaluated with a set of benzodiazepine molecules, using the two-dimensional molecular structure as the only a priori input. The overall trend in intrinsic solubility was correctly predicted for the entire set of benzodiazepines molecules. The results also indicate that, in drug compound series where the melting point is relatively high (i.e., "brick dust" compounds), the reported methodology should be very suitable for identifying strategically important molecular substitutions to improve solubility. As such, this approach could be a useful predictive tool for rational compound design in the early stages of drug development.

Solid-state amorphization of linaprazan by mechanical milling and evidence of polymorphism.

In this paper, we study the thermodynamic and structural changes of crystalline linaprazan (a proton pump inhibitor) upon high-energy ball milling at room temperature. The investigations have been performed by differential scanning calorimetry and powder X-ray diffraction. The results indicate that this drug undergoes a direct crystal-to-glass transformation upon milling. Moreover, upon heating, the amorphous material obtained by milling is shown to recrystallize toward two different polymorphs that appear to form a monotropic set.