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Updated: Jun 24, 2026

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water
Published on: August 2, 2012
Highly supersaturated solutions of amorphous drugs approaching predictions from configurational thermodynamic
Michal E Matteucci1, Maria A Miller, Robert O Williams
1Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA.
Abstract:
Dissolution of pure solid itraconazole in metastable amorphous states was used to produce high supersaturation in low pH media. For a prewet dispersion of particles on the order of 1 microm produced by antisolvent precipitation, an experimental supersaturation of 63 times the crystalline solubility was achieved. This experimental value approached the calculated value of 95 from the configurational free energy, G(conf), which was determined from modulated differential scanning calorimetry measurements. A high fragility, quantitatively determined by the fragility parameter, gamma(cp), is dependent on the configurational heat capacity, C(pconf), favoring a high G(conf) and thus high supersaturation. However, high fragility also increases the driving force for crystallization of the solid during dissolution. The relatively fragile prewet dispersions dissolved rapidly and produced high supersaturation without crystallizing, in contrast with much lower supersaturation values for slowly dissolving particles with low wetted-surface areas formed by spray drying or lyophilization of aqueous dispersions.
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