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Deformation Behaviors of Tolbutamide, Hydroxypropyl-β-Cyclodextrin, and Their Dispersions

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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.

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Authors and Affiliations

  1. Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland

    Eero Suihko

  2. Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland

    Antti Poso, Ossi Korhonen, Jukka Gynther, Jarkko Ketolainen & Petteri Paronen

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Suihko, E., Poso, A., Korhonen, O. et al. Deformation Behaviors of Tolbutamide, Hydroxypropyl-β-Cyclodextrin, and Their Dispersions. Pharm Res 17, 942–948 (2000). https://doi.org/10.1023/A:1007523103979

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