Solid-state chemistry of pharmaceutical co-crystals, amino acids and other materials

Abstract

This thesis reports structural and thermal properties of organic solids, focusing on pharmaceutical co-crystals and amino acids. Structural properties were determined primarily using state-of-the-art techniques for carrying out structure determination from powder X-ray diffraction (XRD) data, as well as using single-crystal XRD and solid-state NMR spectroscopy. Thermal properties were investigated using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Chapter 1 gives background information on co-crystals and their applications, and the important topic of polymorphism is highlighted. Chapter 2 discusses theoretical aspects of experimental techniques used in this thesis, including XRD (both single-crystal and powder XRD), solid-state NMR, DSC and TGA. Chapter 3 describes the procedures for carrying out structure determination directly from powder XRD data, including details of the indexing, profile fitting, structure solution and structure refinement stages of the structure determination process. The use of periodic DFT-D calculations in conjunction with structure determination from powder XRD data is also discussed. Chapter 4 explores structural properties, thermal properties and hydration-dehydration behaviour of two solid forms of the pharmaceutical co-crystal system (S)-ibuprofen:L-lysine. Interconversion between the two forms, which are anhydrous and monohydrate phases, is also established. Chapter 5 reports structural and thermal properties of two solid forms of the pharmaceutical co-crystal system (S)-ibuprofen:L-proline. One form is an elusive anhydrous phase (obtained only once), while the other form is a quarter-hydrate that is obtained reproducibly. The dehydration behaviour of the quarter-hydrate form has been investigated. Chapter 6 describes structural properties of a new polymorph of L-tryptophan prepared in this work, giving a detailed comparison to the structure of the previously reported polymorph. Periodic DFT-D calculations are used to assess the relative energetic properties of the two polymorphs. ii Chapter 7 is focused on structural characterization of 1-iodoadamantane as a function of temperature, a material that exhibits complex phase transition behaviour