Probing the interaction and structural arrangement of medicinal compounds confined in novel, amorphous drug delivery systems

 

Ken K. Qian, Katharine L. Page, Wei Zhou, and Terrence J. Udovic

 

Amorphous solids are of significant interest in pharmaceutical product development.  A drug in an amorphous state has the desirable properties such as enhanced aqueous solubility and dissolution rate, in comparison to its corresponding crystalline phase.  However, the commercial application of pharmaceutical amorphous solids has not been widely explored because of their strong tendency to crystallize to a thermodynamically more stable form, thus offsetting the benefit of amorphization.  Mesoporous materials, with mean pore diameters between 2 nm and 50 nm, have received considerable interest as novel, amorphous drug delivery systems.  A striking advantage is that when drug molecules are confined within the nano-sized capillaries, crystallization can be completely inhibited.   

 

A thorough knowledge of molecular interactions and structural arrangements of drug molecules in the pores is critical to the fundamental understanding and industrial application of this type of pharmaceutical system.  We used X-ray diffraction, total scattering, and pair distribution function to probe the disordered structural arrangement of molecules residing inside of the pores.  Furthermore, we studied the interactions between drug molecules and mesoporous materials using neutron vibrational spectroscopy in conjunction with first-principles phonon calculations.  Experimental evidence showed that crystalline drugs became amorphous once the molecules were incorporated into the nano-sized capillaries.  For example, in the case of ibuprofen confined within mesoporous silica, the results suggested that ibuprofen molecules preferentially adsorbed on the pore surfaces, forming hydrogen bonds between their functional groups and the surface hydroxyl groups of the porous medium rather than crystallizing into an ordered arrangement of ibuprofen dimers, as observed in the bulk.