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Published on: August 2, 2012
Deformation behaviors of tolbutamide, hydroxypropyl-beta-cyclodextrin, and their dispersions
1Department of Pharmaceutics, University of Kuopio, Finland. Eero.Suihko@uku.fi
Purpose:
The deformation behaviors of compressed freeze-dried and spray-dried tolbutamide/hydroxypropyl-beta-cyclodextrin molecular dispersions were evaluated and compared with similarly prepared tolbutamides (TBM), hydroxypropyl-beta-cyclodextrins (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 Heckel plots. Molecular dynamics (MD) simulations were performed in order to gain a molecular-level view on the deformation behavior of TBM-HP-beta-CD inclusion 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 molecular dispersions decreased the plastic and elastic behaviors of these materials. Also, the MD simulations showed a reduced molecular flexibility of the TBM-HP-beta-CD inclusion complex, as compared to HP-beta-CD.
Conclusions:
The formation of TBM and HP-beta-CD molecular dispersion resulted in more rigid molecular arrangements, which were less prone to deformation than either HP-beta-CDs or physical dispersions. The results showed how differing molecular, solid, particle, and powder state properties affect the deformation properties of the materials studied.
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