Deformation behaviors of tolbutamide, hydroxypropyl-beta-cyclodextrin, and their dispersions.
OBJECTIVE
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.
Suihko
E
E
Department of Pharmaceutics, University of Kuopio, Finland. Eero.Suihko@uku.fi
Poso
A
A
Korhonen
O
O
Gynther
J
J
Ketolainen
J
J
Paronen
P
P
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003505:Cyclodextrins / Q000737:chemistry*; D004339:Drug Compounding; D005612:Freeze Drying; D007004:Hypoglycemic Agents / Q000737:chemistry*; D008958:Models, Molecular; D010316:Particle Size; D011208:Powders; D014044:Tolbutamide / Q000737:chemistry*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D007004:Hypoglycemic Agents; D011208:Powders; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014044:Tolbutamide