Tasnim Munshi

Identification of a new cocrystal of citric acid and paracetamol of pharmaceutical relevance

Cocrystals have been increasingly recognized as an attractive alternative delivery form for solid drug products. In this work, Raman spectroscopy, X-ray powder diffraction/X-ray crystallography, and differential scanning calorimetry have been used to study the phenomenon of cocrystal formation in stoichiometric mixtures of citric acid with paracetamol. Raman spectroscopy was particularly useful for the characterization of the products and was used to determine the nature of the interactions in the cocrystals. It was observed that little change in the vibrational modes associated with the phenyl groups of the respective reactants took place upon cocrystal formation but changes in intensities of the vibrational modes associated with the amide and the carboxylic acid groups were observed upon cocrystal formation. Several new vibrational bands were identified in the cocrystal which were not manifest in the raw material and could be used as diagnostic features of cocrystal formation. An understanding of the effects of cocrystal formation on the vibrational modes was obtained by the complete assignment of the spectra of the starting materials and of the cocrystal component. The results show that the cocrystals was obtained in a 2 : 1 molar ratio of paracetamol to citric acid. The asymmetric unit of the crystal contains two paracetamol molecules hydrogen-bonded to the citric acid; one of these acts as a phenolic-OH hydrogen bond donor to the carbonyl of a carboxylic acid arm of citric acid. In contrast, the other phenolic-OH acts as a hydrogen bond acceptor from the quaternary C–OH of citric acid.

Identification of a new co-crystal of salicylic acid and benzamide of pharmaceutical relevance

Raman spectroscopy, X-ray powder diffraction/X-ray crystallography and differential scanning calorimetry have been used to study the phenomenon of co-crystal formation in stoichiometric mixtures of salicylic acid with benzamide. Raman spectroscopy was particularly useful for the characterization of the products and was used to determine the nature of the interactions in the co-crystals. It was observed that little change in the vibrational modes associated with the phenyl groups of the respective reactants took place upon co-crystal formation, but changes in intensities of the vibrational modes associated with the amide and the carboxylic acid groups were observed upon co-crystal formation. Several new vibrational bands were identified in the co-crystal which were not manifested in the physical mixture of both components and could be used as diagnostic features of co-crystal formation.

Broadband terahertz time-domain and Raman spectroscopy of explosives

Broadband terahertz time-domain spectroscopy (THz-TDS) has been shown to be a valuable technique for the detection and analysis of explosives. In this paper, we present recent work on the use of this technique to analyse two pure explosives, 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and 1,3-dinitrato-2,2-bis(nitratomethyl)propane (PETN) and three plastic explosives (Semtex, SX2 and Metabel). For each explosive, a clear and unique spectral absorption fingerprint is found, which can be attributed to oscillations of the molecular lattice. Temperature dependent terahertz absorption measurements of RDX show that the observed vibrational modes are anharmonic in nature. Terahertz spectra are compared with Raman spectra, and the similarities and differences between the spectra produced by the two techniques are discussed. A molecular mechanics calculation approach is used to calculate vibrational intensities and frequencies, and these results are compared with experimental results at both room temperature and 4 K.

A forensic case study: the detection of contraband drugs in carrier solutions by Raman spectroscopy

Recently, cocaine has been concealed by dissolving it in alcohol and then transporting it in solution through ports and airports. At the present time it is very difficult to detect cocaine in this form in these environments. However, it has been shown that Raman spectroscopy can successfully detect the presence of these drugs without removing specimens from their containers. Using two portable 785 nm instruments and a 1064 nm laboratory-based instrument, several common containers used in smuggling were analyzed with varying concentrations of cocaine in ethanol solutions. The presence of cocaine is detectable to about 6% w/v in most containers. Green glass presents a problem at 785 nm due to fluorescence but by switching to 1064 nm this can be removed. To apply this technique to real samples as met within law enforcement scenarios, cocaine was dissolved in a selection of dark and white rums including Lambs Navy Rum(™) , Brugal Añejo(™) , Bacardi(™) and Captain Morgan(™) ; cocaine was detected in all these rum solutions.

Building multi-component crystals from cations and co-crystals: the use of chaperones

Ternary crystalline complexes consisting of both salts and ionic co-crystals have been created through the crystallisation of the binary co-crystal 3,5-dinitrobenzoic acid–4-(dimethylamino)benzoic acid with group 1 or ammonium cations. The size and charge density of the cation can be used to adjust the protonation level and local geometry of the acid pair. The selectivity and coordination geometry of the chaperone cation may be further adjusted by the inclusion of a crown ether to reduce the number and location of potential binding sites.

Vibrational spectroscopic characterisation of salmeterol xinafoate polymorphs and a preliminary investigation of their transformation using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry

Knowledge and control of the polymorphic phases of chemical compounds are important aspects of drug development in the pharmaceutical industry. Salmeterol xinafoate, a long acting beta-adrenergic receptor agonist, exists in two polymorphic Forms, I and II. Raman and near infrared spectra were obtained of these polymorphs at selected wavelengths in the range of 488-1064 nm; significant differences in the Raman and near-infrared spectra were apparent and key spectral marker bands have been identified for the vibrational spectroscopic characterisation of the individual polymorphs which were also characterised with X ray diffractometry. The solid-state transition of salmeterol xinafoate polymorphs was studied using simultaneous in situ portable Raman spectroscopy and differential scanning calorimetry isothermally between transitions. This method assisted in the unambiguous characterisation of the two polymorphic forms by providing a simultaneous probe of both the thermal and vibrational data. The study demonstrates the value of a rapid in situ analysis of a drug polymorph which can be of potential value for at-line in-process control.

Complementary spectroscopic studies of materials of security interest

We demonstrate that, through coherent measurement of the transmitted terahertz frequency electric fields, broadband (0.3 - 8 THz) time-domain spectroscopy can be used to measure far-infrared vibrational modes of a range of drugs-of-abuse and high explosives that are of interest to the forensic and security services. Our results indicate that absorption features in these materials are highly sensitive to the structural and spatial arrangement of the molecules. Terahertz frequency spectra are also compared with high-resolution low-frequency Raman spectra to assist in understanding the low-frequency inter- and intra-molecular vibrational modes of the molecules.

Multi-component crystals of 4-phenylpyridine: challenging the boundaries between co-crystal and organic salt formation with insight into solid-state proton transfer

Six new multi-component crystals between 4-phenylpyridine and substituted benzoic acids (3-nitrobenzoic acid, 3,5-dinitrobenzoic acid, gallic acid, 4-aminobenozic acid, salicylic acid and 2-aminobenzoic acid) were created and characterized crystallographically to investigate the influence of chemical and structural factors on the hydrogen location between the two components. While the expected intermolecular interactions are formed between the acid and pyridine group in most cases, the gallic acid structure is anomalous forming an unexpected salt with pyridine to hydroxyl interactions. Calculations of the hydrogen bonding motifs indicate that the level of proton transfer (e.g. salt versus co-crystal formation) is not solely a function of the dimer geometry but influenced by the local crystallographic environment. Analysis of the crystal structures indicates the strength of the hydrogen bonding into this motif alters the expected protonation state from chemical considerations.

Raman spectra of biomarkers of relevance to analytical astrobiological exploration: hopanoids, sterols and steranes.

The aim of this work is to investigate the viability and potential of three groups of organic compounds as biomarkers in a future robotic analytical exploration of Mars. The three compounds have been identified as suitable candidates for potential biomarkers for extant or extinct life from the terrestrial fossil record. The three groups of compound were all similar in structure, being either tetra- or penta-cyclic compounds. The limits of detection for a sample were also tested to estimate what concentrations it would still be amenable to Raman spectroscopic investigation. This was investigated using both solid mixtures and liquid solutions. The spectra of these compounds are characterised so that they can be added to the Raman database for future Mars missions. This involved identifying functional group characteristics, assigning peaks for each individual sample and characteristic features which would categorise the samples.

Analysis of drugs-of-abuse and explosives using terahertz time-domain and Raman spectroscopy

We demonstrate that, through coherent measurement of the transmitted terahertz electric fields, broadband (0.3-8THz) time-domain spectroscopy can be used to measure far-infrared vibrational modes of a range of illegal drugs and high explosives that are of interest to the forensic and security services. Our results show that these absorption features are highly sensitive to the structural and spatial arrangement of the molecules. Terahertz frequency spectra are also compared with high-resolution low-frequency Raman spectra to assist in understanding the low frequency inter- and intra-molecular vibrational modes of the molecules.