Dielectric Study of Equimolar Acetaminophen-Aspirin, Acetaminophen-Quinidine, and Benzoic Acid-Progesterone Molecular Alloys in the Glass and Ultraviscous States and Their Relevance to Solubility and Stability

Equimolar mixtures of acetaminophen-aspirin, acetaminophen-quinidine, and benzoic acid-progesterone have been vitrified and dielectric properties of their glassy and ultraviscous alloys have been studied. For 20 K/min heating rate, their Tgs are 266, 330, and 263 K, respectively. The relaxation has an asymmetric distribution of times, and the distribution parameter increases with increase in temperature. The dielectric relaxation time varies with T according to the Vogel-Fulcher-Tammann equation, log10(τ0) = AVFT + [BVFT/(T − T0)], where AVFT, BVFT, and T0 are empirical constants. The equilibrium permittivity is highest for the aspirin-acetaminophen and lowest for the benzoic acid‐progesterone alloy, indicating a substantial interpharmaceutical hydrogen bonding that makes the alloy more stable against crystallization than the pure components. The benzoic acid-progesterone alloy is thermodynamically the most nonideal. It showed cold crystallization on heating, which is attributed to its relatively greater magnitude of the JG relaxation in relation to its α‐relaxation. It is argued that the difference between the free energy of an alloy and the pure components would have an effect on the solubility. Studies of solution thermodynamics of a glassy molecular alloy may be useful for optimizing choice of components and composition to form molecular alloys and to impact drug delivery. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1358-1374, 2010