X-ray and Neutron Diffraction in the Study of Organic Crystalline Hydrates

Abstract

A review. Diffraction methods are a powerful tool to investigate the crystal structure of organic compounds in general and their hydrates in particular. The laboratory standard technique of single crystal X-ray diffraction gives information about the molecular conformation, packing and hydrogen bonding in the crystal structure, while powder X-ray diffraction on bulk material can trace hydration/dehydration processes and phase transitions under non-ambient conditions. Neutron diffraction is a valuable complementary technique to X-ray diffraction and gives highly accurate hydrogen atom positions due to the interaction of the radiation with the atomic nuclei.Although not yet often applied to organic hydrates, neutron single crystal and neutron powder diffraction give precise structural data on hydrogen bonding networks which will help explain why hydrates form in the first place.

Preparation and evaluation of three mucoadhesive dosage forms using 99mTc–Ofloxacin

“…Each XRD pattern was characterized by the interplanar d-spacing and the relative intensities (I/I 0 ) of the three strongest peaks in the pattern under the Hanawalt system. While the relative intensities of drug and formulation were different, their corresponding d-values were nearly identical, as also reported earlier by others (Fucke and Steed, 2010). Their XRD data indicates the retention of crystalline nature of Ofloxacin in all the formulations, leading to increase in stability and drug loading, decrease in solubility and delayed release of the drug from polymeric suspensions with better bioavailability and penetration capacity.…”

Structural Analysis of Ciprofloxacin-Carbopol Polymeric Composites by X-Ray Diffraction and Fourier Transform Infra-Red Spectroscopy

“…The characteristic set of dspacings generated in a typical x-ray scan provides a unique "fingerprint" of the drug molecule present in the sample. When properly interpreted, by comparing with pure drug as reference, this "fingerprint" allows for identification and change in crystallinity of the drug present in the polymeric composite [2].…”

“…X-ray powder diffractometry (XRPD) can often be carried out to monitor structural changes in a solid with a high degree of accuracy in relation to conditions such as temperature, pressure or exposure to gaseous atmospheres of varying composition, including relative humidity [1][2][3]. XRPD is a useful qualitative tool in the pharmaceutical industry for studying the crystal morphology of active ingredients and polymers singly or in a mixture [3,4].…”

The role of co-crystals in pharmaceutical design

“…3 ) and a reactor or spallation neutron source (53). Of particular relevance to co-crystal research is the issue of proton transfer; a stoichiometric crystal containing a neutral acid such as a carboxylic acid, along with a free base drug substance is a co-crystal.…”

“…Since hydrogen atoms are difficult to locate by X-rays, the expensive and challenging alternative of single crystal neutron diffraction may be required (53). An extensive range of inorganic and coordination complex salt co-crystals (or ionic co-crystals (63)) have been prepared by Braga and coworkers, who discovered that grinding an organometallic carboxylic acid with KBr resulted in the formation of a crystalline molecular KBr adduct (64).…”