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Role of Viscosity in Influencing the Glass-Forming Ability of Organic Molecules from the Undercooled Melt State

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ABSTRACT

Purpose

Understanding the critical factors governing the crystallization tendency of organic compounds is vital when assessing the feasibility of an amorphous formulation to improve oral bioavailability. The objective of this study was to investigate potential links between viscosity and crystallization tendency for organic compounds from the undercooled melt state.

Methods

Steady shear rate viscosities of numerous compounds were measured using standard rheometry as a function of temperature through the undercooled melt regime. Data for each compound were fit to the Vogel-Tamman-Fulcher (VTF) equation; kinetic fragility via strength parameter (D) was determined.

Results

Compounds with high crystallization tendencies exhibited lower melt viscosities than compounds with low crystallization tendencies. A correlation was observed between rate of change in viscosity with temperature and crystallization tendency, with slowly crystallizing compounds exhibiting larger increases in viscosity as temperature decreased below Tm. Calculated strength parameters indicated all compounds were kinetically fragile liquids; thus, kinetic fragility may not accurately assess glass-forming ability from undercooled melt state.

Conclusions

A link was observed between the viscosity of a compound through the undercooled melt regime and its resultant crystallization tendency, indicating viscosity is a critical parameter to fully understand crystallization tendency of organic compounds.

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ACKNOWLEDGMENTS & DISCLOSURES

The authors would like to thank the National Science Foundation Engineering Research Center for Structured Organic Particulate Systems (NSF ERC-SOPS) (EEC-0540855) for financial support. This work was funded in part by a grant from the Lilly Endowment, Inc., to Purdue University College of Pharmacy. The American Foundation for Pharmaceutical Education (AFPE) is acknowledged for a fellowship to JAB. The Purdue Graduate School is acknowledged for the Ross fellowship to JAB.

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana, 47907, USA

    Jared A. Baird & Lynne S. Taylor

  2. Department of Chemical Engineering, University of Puerto Rico-Mayagüez, PO Box 9000, Mayagüez, Puerto Rico, 00681, USA

    Darlene Santiago-Quinonez & Carlos Rinaldi

Authors
  1. Jared A. Baird
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  2. Darlene Santiago-Quinonez
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  3. Carlos Rinaldi
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  4. Lynne S. Taylor
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Correspondence to Lynne S. Taylor.

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Baird, J.A., Santiago-Quinonez, D., Rinaldi, C. et al. Role of Viscosity in Influencing the Glass-Forming Ability of Organic Molecules from the Undercooled Melt State. Pharm Res 29, 271–284 (2012). https://doi.org/10.1007/s11095-011-0540-4

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  • DOI: https://doi.org/10.1007/s11095-011-0540-4

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