08. Mai 2014 : Morphology of Porous Hosts Directs Preferred Polymorph Formation and Influences Kinetics of Solid/Solid Transitions of Confined Pharmaceuticals
G.Graubner, G. T. Rengarajan, N. Anders, N. Sonnenberger, D. Enke, M. Beiner, M. Steinhart Cryst. Growth Des. 2014, 14, 78 DOI: 10.1021/cg401170m From the Abstract: 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.
Morphology of porous hosts directs preferred polymorph formation and influences ki-netics of solid/solid transitions of confined pharmaceuticals
The pore morphology of a porous host may determine which polymorph a crystallisable 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 aluminium 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 nu-cleation at bulk crystals formed in the bulk surface film on top of the AAO coupled with ki-netic 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 sponge-like pores (tortuosity > 1.5) with free growth paths of 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 for-mation of form II grains with different orientations separated by energetically disadvanta-geous grain boundaries. The results reported here are relevant to mesoscopic crystal engineer-ing aiming at controlled drug release from nanoscale delivery systems. Polymorphs not acces-sible otherwise in nanoscale containers may be produced at high yields. The principles re-ported here may be transferred to areas such as nanowire-based organic electronics.
Gitte Graubner, Gopalakrishnan Trichy Rengarajan, Nicole Anders, Nicole Sonnenberger, Dirk Enke, Mario Beiner, Martin Steinhart, Cryst. Growth Des. 2014, 14, 78; DOI: 10.1021/cg401170m