186 research outputs found
X-ray crystallography and its role in understanding physicochemical properties of pharmaceutical cocrystals
YesProperties of a matter are intrinsically dependent upon the internal arrangement of molecules in the solid state. Therefore, knowledge of 3-dimensional structure of the matter is prerequisite for structure-property correlations and design of functional materials. Over the past century, X-ray crystallography has evolved as a method of choice for accurate determination of molecular structure at atomic resolution. The structural information obtained from crystallographic analysis paved the way for rapid development in electronic devices, mineralogy, geosciences, materials science, pharmaceuticals, etc. Knowledge of the structural information of active pharmaceutical ingredients (APIs) is prerequisite for rational drug design and synthesis of new chemical entities for development as new medicines. Over the past two decades, X-ray crystallography has played a key role in the design of pharmaceutical cocrystals-crystalline solids containing an API and one or more of pharmaceutically acceptable coformers. These materials have proved promising for fine-tuning several important properties of APIs. This short review highlights the history of crystallography, early breakthroughs, and the role of crystallography in understanding physicochemical properties of pharmaceutical cocrystals.S. Aitipamula gratefully acknowledges the financial support from the Institute of Chemical and Engineering Sciences of A*STAR (Agency for Science, Technology and Research), Singapore. V. R. Vangala thanks Royal Society of Chemistry for Researcher Mobility Grant (2015/17)
Indirect Wafer Bonding and Epitaxial Transfer of GaSb-Based Materials
Results from a study of indirect wafer bonding and epitaxial transfer of GaSb-based materials are presented. Benzocyclobutene (BCB) was used as a bonding agent to bond GaSb and epitaxial structures lattice matched to GaSb onto Si, GaAs, and sapphire carrier substrates. To better understand sources of stress during the bonding process, which can result in cracking and subsurface damage of the GaSb-based materials, BCB’s hardness and reduced elastic modulus were measured at various stages during the curing process. Based on the results of curing experiments, a bonding and epitaxial transfer process for GaSb-based materials was then developed. Following bonding, using an experimentally determined low-stress cure cycle, GaSb substrates were removed from epitaxial layers of InAsSb using a combination of mechanical thinning and polishing followed by selective chemical etching using a hydrofluoric and chromic acid solution. Etch selectivity data are also presented where selectivity greater than 100:1 is achieved for GaSb:InAsSb
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Isomorphism: 'Molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid
YesThe non-steroidal anti-inflammatory drugs mefenamic acid (MFA) and
tolfenamic acid (TFA) have a close resemblance in their molecular scaffold,
whereby a methyl group in MFA is substituted by a chloro group in TFA. The
present study demonstrates the isomorphous nature of these compounds in a
series of their multicomponent solids. Furthermore, the unique nature of MFA
and TFA has been demonstrated while excavating their alternate solid forms in
that, by varying the drug (MFA or TFA) to coformer [4-dimethylaminopyridine
(DMAP)] stoichiometric ratio, both drugs have produced three different types
of multicomponent crystals, viz. salt (1:1; API to coformer ratio), salt hydrate
(1:1:1) and cocrystal salt (2:1). Interestingly, as anticipated from the close
similarity of TFA and MFA structures, these multicomponent solids have shown
an isomorphous relation. A thorough characterization and structural investigation of the new multicomponent forms of MFA and TFA revealed their
similarity in terms of space group and structural packing with isomorphic nature
among the pairs. Herein, the experimental results are generalized in a broader
perspective for predictably identifying any possible new forms of comparable
compounds by mapping their crystal structure landscapes. The utility of such an
approach is evident from the identification of polymorph VI of TFA from
hetero-seeding with isomorphous MFA form I from acetone–methanol (1:1)
solution. That aside, a pseudopolymorph of TFA with dimethylformamide
(DMF) was obtained, which also has some structural similarity to that of the
solvate MFA:DMF. These new isostructural pairs are discussed in the context of
solid form screening using structural landscape similarityDepartment of Science and Technology (DST/SJF/CSA-02/2014–15); Royal Pharmaceutical Society of Great Britain for seed corn funding (2018–19); INSPIRE fellowship from Department of Science and Technology, Government of India; IISER-Kolkata (instrumental facilities and fellowships
Thermal and in situ x-ray diffraction analysis of a dimorphic co-crystal 1:1 caffeine-glutaric acid
YesSpurred by the enormous interest in co-crystals from the pharmaceutical industry, many novel co-crystals of active pharmaceutical ingredients have been discovered in recent years and this has in turn led to an increasing number of reports on polymorphs of co-crystals. Hence, a thorough characterization and understanding of co-crystal polymorphs is a valuable step during drug development. The purpose of this study is to perform in situ structural analysis and to determine thermodynamic stability of a dimorphic co-crystal system, 1:1 caffeine-glutaric acid (CA-GA, Forms I and II). We performed thermal and structural characterizations by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage microscopy (HSM), slurry and in situ variable temperature X-ray diffraction (VTXRD). For completeness, we have also re-determined crystal structures of CA-GA Forms I and II at 180 K using single crystal X-ray diffraction. Our results revealed that Form II is stable and Form I is metastable at ambient conditions. Further, the results suggest that the dimorphs are enantiotropically related and the transition temperature is estimated to be 79 Celcius degrees.This work was supported by Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research), Singapore
Fostering Community Preparedness to Cope with Drought: new initiatives and results from a study involving ODL and ICT from South Central India
Drought has emerged as a key concern in the context of climate variability induced by Climate
Change processes and over a billion people are vulnerable, according to UN estimates. Drought
preparedness is recognized as the preferred way to cope over relief, and information is the key.
Improved access to contemporary ICT in the form of mobile phones and the Internet can help
address the challenge of information deficiency in this matter. We have tried to develop an
integrated approach for improving the capacity of rural communities by bringing together
agricultural information with methods of ODL and effective exchange or delivery using video-
conferencing. This has also enabled skill building among vulnerable rural communities in the use
of color-coded maps derived from satellite imagery and GIS platforms. ICRISAT in partnership
with a community based all- women micro-credit organization, the Adarsha Mahila Samaikhya
(AMS), in South Central India has developed this blend of techniques to help the AMS and rural
communities to anticipate how vulnerable their villages would be to drought in a season. This is
an ongoing partnership, and we report here on joint studies carried out during March 2008-
September 2009
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Solid-State Competitive Destabilization of Caffeine Malonic Acid cocrystal: Mechanistic and Kinetic Investigation
YesThe main objective of this research is to investigate solid-state destabilization mechanism and kinetics of the model cocrystal caffeine : malonic acid (CA:MO) in presence of oxalic acid (OX) as a structural competitor. Competitive destabilization of CA:MO and subsequent formation of CA:OX takes place at temperatures significantly below its melting point. Destabilization mechanism was found to be mediated by sublimation of both CA:MO and OX. During CA:MO destabilization, free CA could not be detected and direct transformation to CA:OX cocrystal was observed. The destabilization kinetics follow Prout-Tompkins nucleation and crystal growth model with activation energy of 133.91 kJ/mol and subsequent CA:OX growth kinetic follow Ginstling – Brounshtien diffusion model with activation energy of kJ/mol
AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.
Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (
Crystal structure and packing analysis of nitrofurantoin N,N-dimethylformamide solvate
Bacterial Distribution in the Rhizosphere of Wild Barley under Contrasting Microclimates
Background: All plants in nature harbor a diverse community of rhizosphere bacteria which can affect the plant growth. Our samples are isolated from the rhizosphere of wild barley Hordeum spontaneum at the Evolution Canyon (‘EC’), Israel. The bacteria which have been living in close relationship with the plant root under the stressful conditions over millennia are likely to have developed strategies to alleviate plant stress. Methodology/Principal Findings: We studied distribution of culturable bacteria in the rhizosphere of H. spontaneum and characterized the bacterial 1-aminocyclopropane-1-carboxylate deaminase (ACCd) production, biofilm production, phosphorus solubilization and halophilic behavior. We have shown that the H. spontaneum rhizosphere at the stressful South Facing Slope (SFS) harbors significantly higher population of ACCd producing biofilm forming phosphorus solubilizing osmotic stress tolerant bacteria. Conclusions/Significance: The long-lived natural laboratory ‘EC ’ facilitates the generation of theoretical testable and predictable models of biodiversity and genome evolution on the area of plant microbe interactions. It is likely that the bacteria isolated at the stressful SFS offer new opportunities for the biotechnological applications in our agro-ecologica
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