ISSN:
1573-904X
Keywords:
Hydroxypropyl-β-cyclodextrin
;
tolbutamide
;
inclusion complex
;
physico-technical properties
;
deformation properties
;
molecular dynamics simulation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. The deformation behaviors of compressedfreeze-dried and spray-dried tolbutamide/hydroxypropyl-β-cyclodextrinmolecular dispersions were evaluated and compared with similarly preparedtolbutamides (TBM), hydroxypropyl-β-cyclodextrins (HP-β-CD) and astheir physical dispersions. Methods. TBM, HP-β-CD, and their 1:1 moleculardispersions were prepared by freeze-drying and spray-drying, and physicaldispersions of TBM and HP-β-CD were blended. Deformation properties ofthe prepared materials were evaluated by using a compaction simulator andconstants derived from Heckel plots. Molecular dynamics (MD) simulationswere performed in order to gain a molecular-level view on the deformationbehavior of TBM-HP-β-CD inclusion complex. Results. The freeze-dried TBM polymorphic form II was lessprone to overall particle deformation than the spray-dried stable form I.Formation of molecular dispersions decreased the plastic and elasticbehaviors of these materials. Also, the MD simulations showed a reducedmolecular flexibility of the TBM-HP-β-CD inclusion complex, as comparedto HP-β-CD. Conclusions. The formation of TBM and HP-β-CDmolecular dispersion resulted in more rigid molecular arrangements, whichwere less prone to deformation than either HP-β-CDs or physicaldispersions. The results showed how differing molecular, solid, particle,and powder state properties affect the deformation properties of thematerials studied.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007523103979
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