A crystallographic and thermal study of pridinol mesylate and its monohydrated solvate

Herein are reported the crystal and molecular structures of the pridinol mesylate salt (C20H25NO+·CH3O3S−) (I) and its monohydrated solvate form (C20H25NO+·CH3O3S−·H2O) (II). A comparison of both with the already reported structure of pure pridinol [1,1-diphenyl-3-piperidino-1-propanol, C20H25NO; Tacke et al. (1980). Chem. Ber. 113, 1962–1980] is made. Molecular structures (I) and (II) are alike in bond distances and bond angles, but differ in their spatial conformation, and, more relevant still, in their hydrogen-bonding motifs. This gives rise to quite different packing schemes, in the form of simple dimers in (I) but water-mediated hydrogen-bonded chains in (II). The dehydration behaviour of form (II) is highly dependent on the heating rate, with slow rates leading to a clear endothermic dehydration step, towards anhydrous (I), with subsequent melting of this latter phase. Increased heating rates result in a more unclear behaviour ending in a structural collapse (melting of the hydrated phase), at temperatures significantly lower than the melting point of the anhydrous phase. The eventual relevance of the water link in the structure of (II) is discussed in regard to this behaviour.

Exploration of the polymorph landscape for 1,1,4,4-tetraphenyl-1,3-butadiene

The solid state behaviour of 1,1,4,4-tetraphenyl-1,3-butadiene (TPB), a well-known blue luminescent molecule, is presented. The crystal structures of four polymorphs and one solvate form are discussed and the experimental occurrence of the four polymorphs is rationalized.

Crystal Structure Data for Efavirenz (Sustiva™) by Combined Synchrotron X-Ray Diffraction and Electron Microscopy Techniques

Efavirenz (Sustiva™) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HrV-infected patients and has been in the market since 1998. Efavirenz exists as three different polymorphs (Forms I, II, III) and a nonstochiometric heptane solvate (Form IV). The current synthetic process for Efavirenz yields Form IV which is converted to the desired Form I polymorph by heating. One of the concerns for any drug substance is whether a consistent crystal form is produced in order to insure consistent physical and chemical properties, as well as to safeguard pharmacokinetic profiles. The sensitivity and resolution of single-crystal x-ray diffraction, the traditional method employed to determine unit cell parameters of drug compounds in development, are limited for Efavirenz Form IV because of the small crystallite size of the material. Furthermore, Efavirenz Form IV materials, depending on the process conditions, have slightly different powder diffraction patterns in terms of intensity when collected on standard in-house diffractometers.