Performance evaluation of two Raman instruments for unknown forensic samples

The Misuse of Drugs Act 1971 classifies Class A, B and C drugs as illegal and over 30000 Class A seizures were reported in England and Wales in 2013/14.1 The drug substance is typically formulated with an array of cutting agents, e.g. Benzocaine, Lidocaine and Phenacetin, leading to a complex mixture of organic species. Early attempts to automate identification of such materials were hampered by spectral overlap and interference. However, developments in computational deconvolution of a spectral data has led to the development of systems that potentially identify targeted components in complex mixtures.2 In this work, a Handheld Raman instrument (Thermo-TruNarc), incorporating an implementation of such an algorithms, was tested with an array of seized samples from UK forensic investigation. These ‘street’ samples were unmodified from seizure and presented as powders (43 samples) and oil (1 sample). The spectral output of the Handheld system was compared with spectra from a laboratory micro-Raman instrument obtained from at least three sites in each sample. Spectra from the laboratory system were assigned and the results compared to the identification reported from the portable system. In 39/44 of cases a valid identification was obtained although, of these, 12 required a sample treatment with an ethanol extraction followed by evaporation onto a proprietary SERS substrate (‘Test-Stick’ analysis). A detailed evaluation of spectral features was undertaken for all cases and where assignments were inconclusive after direct sampling these were mainly attributed to sample fluorescence. Hence, the TruNarc system was shown to be reliable and capable of identifying complex street sample and such identification are available to users with the minimum of spectroscopic expertise

Creation of a ternary complex between a crown ether, 4-aminobenzoic acid and 3,5-dinitrobenzoic acid

YesThe creation of ternary multi-component crystals through the introduction of 18-crown-6 to direct the hydrogen-bonding motifs of the other molecular components was investigated for 3,5-dinitrobenzoic acid (3,5-dnba) with 4-aminobenzoic acid (4-aba). The creation of a binary complex between 18-crown-6 and 4-aba (C12H24O6·2C7H7NO2)2 and a ternary salt between 3,5-dnba, 18-crown-6 and 4-aba (C12H24O6·C7H8NO2+·C7H3N2O6−·C7H4N2O6) were confirmed by single-crystal structure determination. In both structures, the amino molecules bind to the crown ether through N—H...O hydrogen bonds, leaving available only a single O atom site on the crown with restricted geometry to potentially accept a hydrogen bond from 3,5-dnba. While 3,5-dnba and 4-aba form a binary co-crystal containing neutral molecules, the shape-selective nature of 18-crown-6 preferentially binds protonated amino molecules, thereby leading to the formation of the ternary salt, despite the predicted low concentration of the protonated species in the crystallizing solution. Thus, through the choice of crown ether it may be possible to control both location and nature of the available bonding sites for the designed creation of ternary crystals

Beta-cyclodextrin (CD) inclusion complexes of disconnected synthetic cannabinoid molecules

SERS has proven to be a powerful screening technique for synthetic cannabinoids. Research shows successful capping of silver nanoparticles with thiolated CDfor the detection of polycyclic aromatic hydrocarbons for SERS enhancement. CD is an oligosaccharide composed of seven α-D-glucopyranoside units and is commonly used in pharmaceuticals and drug delivery as its cavity can be used to form inclusion complexes with hydrophobic molecules

Rational Development of a Carrier-Free Dry Powder Inhalation Formulation for Respiratory Viral Infections via Quality by Design: A Drug-Drug Cocrystal of Favipiravir and Theophylline

Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality- by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir–theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals with concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal Xray diffraction, powder X-ray diffraction, and the construction of a temperature–composition phase diagram. A three-factor, two-level, full factorial design was employed to produce the optimized formulation and study the impact of critical processing parameters on the resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93 μm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in A549 cells

First Comparative Study of the Three Polymorphs of Bis(isonicotinamide) Citric Acid Cocrystals and the Concomitant Salt 4‑Carbamoylpyridinium Citrate Isonicotinamide

This contribution presents a previously unreported example and comparative study of a binary crystalline adduct that exhibits concomitant salt and cocrystal forms. Specifically, three new polymorphs (α, β, γ) of a novel 2:1 cocrystal of bis(isonicotinamide) citric acid are reported, and the route to isolating each polymorph from aqueous solution is presented and the crystal chemistry of the system is characterized. In addition, the metastable 2:1 salt (ionic adduct) isolated as a transient (overlapping) phase under crystallization conditions identical to the polymorphs is also presented. As far as the authors can ascertain, this may be the first reported example of a salt−cocrystal−polymorphic concomitant system. A comparative study of the solid form landscape is presented, wherein mapping reveals the unique structural complexity of this multiple form salt−cocrystal concomitant system. The α and β forms are structurally very similar, where comparisons of packing behavior are shown to only be different outside the glide plane. The γ form is very different in structure, where supramolecular chirality is present. In addition, further characterization of the isolated solid-state forms includes thermal, spectroscopic, and computational analysis, all of which are employed to further verify the solid form landscape of the isonicotinamide−citric acid adduct and were found to have an order of stability of β, α, γ, salt, the salt being the metastable form

Rapid preparation of pharmaceutical co-crystals with thermal ink-jet printing

Thermal ink-jet printing (TIJP) is shown to be a rapid (minutes) method with which to prepare pharmaceutical co-crystals; co-crystals were identified in all cases where the co-formers could be dissolved in water and/or water/ethanol solutions

Structural Motifs in Salts of Sulfathiazole: Implications for Design of Salt Forms in Pharmaceuticals APIs

YesThe creation of salts is a frequently used approach for the modification of physicochemical properties of an active pharmaceutical ingredient. Despite the frequency of application, there has been little research into the structural-property relationships of the final material and the nature of the counterion present. This work reports on five new salts of sulfathiazole and compares the energetics of the intermolecular interactions with variation in the crystal packing motifs

PREPARATION OF CHEMICALLY MODIFIED AND HYPERCROSSLINKED MICROSPHERES OF POLY(ACRYLONITRILE-co-DIVINYLBENZENE-80-co-VINYLBENZYLCHLORIDE) AS SORBENTS TO CAPTURE PHARMACEUTICAL RESIDUES

Residues of pharmaceutical are potentially hazardous contaminants to aquatic life and human. Pharmaceutical residues have been detected in Malaysian tropical wastewaters. A challenge therein is the development of enrichment techniques able to extract polar pharmaceutical residues, since these compounds are widely found in aqueous samples yet present particular difficulties in their extraction due to their polar character. Acrylonitrile (AN)-divinylbenzene-80 (DVB-80)-vinylbenzylchloride (VBC) porous terpolymer material was prepared in the present research via precipitation polymerisation method. The porous terpolymer (MNA1) containing chlorine pendant groups was hypercrosslinked via a Friedel Crafts reaction to develop 3D network structure within the terpolymer chains. FT-IR spectrum of MNA1 showed that the chloromethyl groups derived from VBC were consumed, which was consistent with successful hypercrosslinking. The hypercrosslinked porous material was then chemically modified with ethylenediamine (EDA) (MNA2) to develop active functional groups (diamine moisties) along terpolymer chains. FT-IR spectrum showed that a new diamine absorption band appeared after the chemical modification, indicating the nitrile group was successfully converted into diamine moieties. Both experimental spectra was validated and proved by the calculated transmittance spectra. The mono-disperse spherical particles of MNA1 and MNA2 were observed using SEM analysis. Their high specific surface area and polar character (arising from AN residues), make them as potential materials to extract pharmaceutical residues

Pyrrole-chalcone analogues as DNA binding agents

Cancer is a gene mutation in the cell that grows uncontrollably. Many drugs have been successfully developed to treat this disease but could not provide effective solutions for cancer treatment, in which the major problem of these drugs is their cytotoxicity. The usual cancer treatment tends to kills the cancerous cell along with healthy cell around it. An alpha,beta- (α,β-) unsaturated ketone at the core of the chalcone feature provides the basis for the wide range of its biological activities including anticancer effect and can be prepared via Claisen-Schmidt condensation reaction between acetophenone and benzaldehydes with base or acid as catalyst1. Pyrrole-chalcones of 3-(2,5-dimethoxy-phenyl)-1-(1H-pyrrole-3-yl)-propenone (compound 1) and 1-(1H-pyrrol-2-yl)-3-m-tolylpropenone (compound 2) were screened for anticancer properties through deoxyribonucleic acid (DNA) binding assay by Ultraviolet Visible (UV/VIS) absorption spectroscopy. The intrinsic binding constant (Kb) of complexes 1 and 2 with calf-thymus DNA (CT-DNA) are 1.08x103 M-1 and 5.225x103 M-1, respectively. It was found that compound 1 has a higher binding affinity than compound 2 due to methoxyl (-OCH3) group is a better electron donating group with an ability to form intramolecular hydrogen bonding with DNA in comparison to methyl (-CH3) moiety. The UV-Visible titration studies suggest that chalcones bind to DNA via intercalation mechanism as it induces hyperchromic effect as shown in the λmax 2. Results obtained from this work would be very useful in understanding the mechanism of interaction of the Pyrrole-chalcone analogues binding to DNA and serve as preliminary information for the development as a new potential anticancer agents

Spectroscopy, chromatography and microscopic image of 3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (MNYAD_1539) crystals

3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (MNYAD_1539) was synthesized by an Aldol condensation method . MNYAD_1539 was synthesized from two commercially available materials of p-Methoxybenzaldehyde and Acetophenone The physical and chemical properties of MNYAD_1539 was investigated using ATR-FTIR, GCMS and a microscope. The FTIR spectrum of the crude MNYAD_1539 showed the presence of impurities, compared with the crystalline sample. The chromatogram showed that MNYAD_1539 with high purity was produced after re-crystallisation. The current study also found high quality of the transparent needle-like crystal after re-crystallisation