Chlorhexidine/-cyclodextrin inclusion complexes by freeze- and spray-drying: Characterization and behavior in aqueous system

Freeze- and spray-dried inclusion complexes (ICs) of chlorhexidine (CHX) in beta-cyclodextrin were characterized by Fourier transform (FT)-Raman, 1H nuclear magnetic resonance (NMR), and photoacoustic spectroscopy. The active Raman modes of CHX were simulated using the density functional theory. By considering semiempirical calculations, it was observed that the guest penetrates on the wider rim of the host in a proportion of 1:2. We observe from the FT-Raman analysis that the drying method influences the CHX:beta-cyclodextrin conformational adjustment by the rearrangement of hydrophilic biguanides of the guest. The photoacoustic spectroscopy results inferred that the freeze-drying method provided a better inclusion due to a lower interaction between phenyl groups and hexamethylene of CHX. The freeze-dried IC achieved a faster dissolution pattern. These ICs provided immediate drug dissolution profiles in an aqueous medium better than a pure drug. The release profiles of freeze- and spray-dried ICs were explained by Fickian diffusion. These data support further planning and development projects of novel immediate release systems based on CHX.