Confinement in nanoporous host systems with strongly interacting pore walls is shown to be a powerful approach to increase the lifetime of amorphous drugs based on changes in thermodynamics and crystallization kinetics in nano-sized systems.

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.

The tip shape of contact elements in hairy adhesion systems is crucial for proper contact formation and adhesion enhancement. While submicrometer terminal contact elements show much better adhesion performance than their larger counterparts, shaping their tips so as to maximize normal adhesion has remained challenging. We prepared durable nanorod arrays consisting of stiff, highly entangled thermoplastic polymers with rationally shaped tips by replication of anodic aluminum oxide (AAO). Nanorod arrays with pancake-like tips showed pronounced normal dry adhesion already for small loading forces. For small loading forces, adhesion forces significantly exceeded the loading forces. Both the absence of hysteresis in force/displacement curves and the pronounced durability of the nanorods in series of repeated attachment/detachment cycles suggest that the nanorods behave like elastic springs. Experimental load-adhesion curves were reproduced with a modified Schargott-Popov-Gorb (SPG) model, assuming that contacts between probe and individual nanorods are sequentially formed with increasing indentation depth.

The pore morphology of a porous host may determine which polymorph a crystallizable guest preferentially forms and may influence the kinetics of solid/solid transitions. Slow cooling of the drug acetaminophen (ACE) inside the straight cylindrical pores of anodic aluminum oxide (AAO, tortuosity = 1) in contact with a bulk ACE surface film preferentially yields uniformly oriented form II and/or form III crystals. The occurring orientations of form II and form III crystals are characterized by high structural registry along the AAO pores. The uniformly oriented form III crystals inside the AAO pores were readily converted into likewise uniformly oriented form II crystals by a solid/solid transition. Thus, we obtained uniformly oriented form II crystals in AAO at high yields. We suggest that sporadic heterogeneous nucleation at bulk crystals formed in the bulk surface film on top of the AAO coupled with kinetic selection of crystal orientations results in fast growth of properly oriented crystals along the 100 μm deep AAO pores. This mechanism is suppressed in controlled porous glass (CPG) having isotropic spongelike pores (tortuosity > 1.5) with free growth paths on the order of 100 nm, where form I formed instead. Moreover, the transition from form III to form II is suppressed in CPG. Possible reasons may include impingement of the propagation front of the solid/solid transition on the CPG pore walls after short propagation paths and inevitable formation of form II grains with different orientations separated by energetically disadvantageous grain boundaries. The results reported here are relevant to mesoscopic crystal engineering aimed at controlled drug release from nanoscale delivery systems. Polymorphs not accessible otherwise in nanoscale containers may be produced at high yields. The principles reported here may be transferred to areas such as nanowire-based organic electronics.