Size-dependent growth of polymorphs in nanopores and Ostwald's step rule of stages.

More than 100 years after Ostwald postulated his step rule of stages, predictive understanding as to early crystallization stages of polymorphic materials is still premature. We studied crystallization of the polymorphic pharmaceutical acetaminophen in nanoporous glasses as a model for early stages of bulk crystallization since the surface energy significantly contributes to the total Gibbs free energy of nanosized crystals in both cases. Systematic studies of transitions between different polymorphs inside nanoporous glasses show that the thermodynamic stability of the polymorphs depends on the crystal size. Accordingly, the transient occurrence of different polymorphs during crystal growth in bulk systems can be related to surface energy contributions to the total Gibbs free energy of the developing crystals. In nanosized early-stage crystals with high surface-to-volume ratios other polymorphs may be stable than in large crystals with low surface-to-volume ratios. Improved control of the crystallization of polymorphic materials by imposing well-defined confinement is a promising strategy to tailor release of polymorphic drugs and to optimize optical, electronic, magnetic and ferroelectric properties of polymorphic materials.

Manipulating the crystalline state of pharmaceuticals by nanoconfinement.

We show that nanoconfinement is a handle to rationally produce and stabilize otherwise metastable or transient polymorphs of pharmaceuticals, as required for controllable and efficient drug delivery. The systematic investigation of crystallization under confinement unveils thermodynamic properties of metastable polymorphs not accessible otherwise and may enhance the understanding of the crystallization behavior of pharmaceuticals in general. As an example in this case, we studied acetaminophen confined to inexpensive and biocompatible nanoporous host systems. Calorimetric and X-ray scattering data clearly evidence that either the stable polymorph form I or the metastable polymorph form III can be stabilized in high yields. Thermodynamic parameters for form III of acetaminophen are reported, and strategies to manipulate the crystalline state in pores by thermal treatments are presented.

Effect of topography on average surface albedo in the ultraviolet wavelength range.

The reflectivity of the 22 km x 24 km region surrounding Sonnblick Observatory near Salzburg, Austria (3104-m altitude, 47.05 degrees N, 12.95 degrees E), was calculated with a three-dimensional albedo model. The average albedo of the region was calculated at 305 and 380 nm for different solar zenith angles, ground reflectances, and solar azimuth angles. To determine geometrical effects, we first carried out the simulations without taking account of the effects of the atmosphere. The ratio to the reflectivity of a corresponding flat surface area (area with the same ground characteristics) was always less than 1 and showed a decrease with increasing solar zenith angle and with diminishing ground reflectance. Even when the ground reflectance was 100%, the average albedo was less than 1. The effect of the atmosphere was then taken into consideration in these calculations and was found to diminish the reflected components. This diminishing effect was compensated for, however, by the scattered irradiance. Finally, simulations of real conditions (nonhomogeneous ground reflectivities) were performed for different snow lines in the Sonnblick region. The average albedos obtained when all the surroundings were covered with snow were 0.32-0.63 with low solar zenith angles and 0.38-0.77 with a 40 degrees solar zenith angle.