Two New Paracetamol/Dioxane Solvates—a System Exhibiting a Reversible Solid‐State Phase Transformation

• Published in: Journal of pharmaceutical sciences 2003-10, Vol.92 (10), p.2069-2073
• Main Authors: Vrcelj, Ranko M., Clark, Nathan I.B., Kennedy, Alan R., Sheen, David B., Shepherd, Evelyn E.A., Sherwood, John N.
• Format: Article
• Language: English
• Subjects: Acetaminophen - chemistry; Analgesics; Biological and medical sciences; Crystallization; crystallography; Crystallography, X-Ray; Dioxanes - chemistry; Medical sciences; Molecular Conformation; Neuropharmacology; Pharmacology. Drug treatments; Phase Transition; polymorphism; solvate; Solvents - chemistry; Temperature
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.10477

This work reports on the crystal structures of two dioxane solvates of paracetamol that are true polymorphs. The high temperature phase is an orthorhombic form, space group Pbca, Z = 8, a = 12.6078(3) Å, b = 12.1129(2) Å, c = 13.4138(3) Å, V = 2048.52(7) Å3, (at 295K) and the low temperature form is monoclinic, space group P21/c, Z = 4, a = 12.325(6) Å, b = 11.965(4) Å, c = 13.384(6) Å, β = 92.01°, V = 1972.6(14)Å3 (at 123K). The structures of these polymorphs are described as is the interrelationship between the two structures. In addition to the structural interrelationship, it is shown that the two forms undergo a reversible phase transformation. Desolvation of either form generates the stable monoclinic phase of paracetamol. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2069–2073, 2003