Deformation behaviors of tolbutamide, hydroxypropyl-beta-cyclodextrin, andtheir dispersions

Purpose. The deformation behaviors of compressed freeze-dried and spray-dri ed tolbutamide/hydroxypropyl-beta-cyclodextrin molecular dispersions were e valuated and compared with similarly prepared tolbutamides (TBM), hydroxypr opyl-beta-cyclodexuins (HP-beta-CD) and as their physical dispersions. Methods. TBM, HP-beta-CD, and their 1:1 molecular dispersions were prepared by freeze-drying and spray-drying, and physical dispersions of TBM and HP- beta-CD were blended. Deformation properties of the prepared materials were evaluated by using a compaction simulator and constants derived from Hecke l plots. Molecular dynamics (MD) simulations were performed in order to gai n a molecular-level view on the deformation behavior of TBM-HP-beta-CD incl usion complex. Results. The freeze-dried TBM polymorphic form II was less prone to overall particle deformation than the spray-dried stable form I. Formation of mole cular dispersions decreased the plastic and elastic behaviors of these mate rials. Also, the MD simulations showed a reduced molecular flexibility of t he TBM-HP-beta-CD inclusion complex, as compared to HP-beta-CD. Conclusions. The formation of TBM and HP-beta-CD molecular dispersion resul ted in more rigid molecular arrangements, which were less prone to deformat ion than either HP-beta-CDs or physical dispersions. The results showed how differing molecular, solid, particle, and powder state properties affect t he deformation properties of the materials studied.