An Etoricoxib Phase Diagram:  Hemihydrate and Anhydrate

Abstract

Anhydrate and hemihydrate phases of etoricoxib (5-chloro-6′methyl-3-[4-(methylsulfonyl)phenyl]-2,3′-bipyridine) are described. The ternary phase diagram of etoricoxib, isopropyl acetate, and water at 10 °C is reported. The critical water/ isopropyl acetate ratio at this temperature, below which etoricoxib will exist as anhydrate at equilibrium, is 0.21 ( 0.04 wt % water, as determined from measurements made on the ternary solution in simultaneous equilibrium with anhydrate and hemihydrate solids.

Thermodynamic Stability and Crystal Structures for Polymorphs and Solvates of Formoterol Fumarate

“…Any hydrate or solvate, which successfully competes against the most stable anhydrate, is also very likely thermodynamically stable at the chosen conditions of temperature, pressure, and solvent. If possible the reversibility of these solvate‐ansolvate or hydrate‐anhydrate equilibria should also be carefully tested by determining the solubility curves in the corresponding binary or ternary phase diagrams 4,6,7 Summing up, a number of reversible relationships between one (monotropic system) or several (enantiotropic system) anhydrates and a number of hydrates and solvates have now been determined (a schematic example is given in Fig.…”

“…Any hydrate or solvate, which successfully competes against the most stable anhydrate, is also very likely thermodynamically stable at the chosen conditions of temperature, pressure, and solvent. If possible the reversibility of these solvate‐ansolvate or hydrate‐anhydrate equilibria should also be carefully tested by determining the solubility curves in the corresponding binary or ternary phase diagrams 4,6,7…”

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“…Etoricoxib, the API used in this study, is a nonhygroscopic low molecular weight proprietary drug used for the treatment of arthritis and pain (Merck Research Laboratories, Rahway, NJ) 22,23. Five anhydrous and two hydrate forms have been discovered to date 24.…”

“…The focus of this article is to characterize the factors contributing to lot dependency on the relative rate of hydrate formation of etoricoxib, a cycloogenase‐2 inhibitor (COX‐2), used for the treatment of osteoarthritis, rheumatoid arthritis, and dental pain 22,23. The relative rate of hydrate formation varied from quite slow (hours) to fast (seconds) with no easily detectable physical or chemical differences.…”

In-line Measurement of a Drug Substance via Near Infrared Spectroscopy to Ensure a Robust Crystallization Process

“…Polymorphism is an important phenomenon because it will affect the physical properties, and may influence other properties such as bio‐availability and stability of a compound 1. Etoricoxib, a highly selective cyclo‐oxygenase II (COX‐2) inhibitor, exhibits polymorphism 2. Spontaneous and uncontrolled crystallization of solids from solution can produce any one of several Etoricoxib polymorphs, or mixtures of them.…”