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Journal of Pharmaceutical Sciences Jan 2022The purpose of this study is to investigate the effects of dry and wet mechanochemical synthesis on piroxicam (PX) and saccharin (SA) mixtures. For this purpose, PX and...
Dry and Wet Mechanochemical Synthesis of Piroxicam and Saccharin Co-Crystals and Evaluation by Powder X-Ray Diffraction, Thermal Analysis and Mid- and Near- Infrared Spectroscopy.
The purpose of this study is to investigate the effects of dry and wet mechanochemical synthesis on piroxicam (PX) and saccharin (SA) mixtures. For this purpose, PX and SA mixtures prepared by wet mechanochemical processes using three solvents and by dry mechanochemical synthesis were evaluated by mid-and near-infrared spectroscopy, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The mixtures of wet-type products were transformed into PX/SA 1:1 co-crystals. The effect of the solvent was key to the co-crystallization of PX and SA. The products from the dry process were transformed into the amorphous phase. For the sample of the amorphous mixture, two exothermic peaks due to crystallization were observed in the thermal analysis. Bulk PX was ground for the same number of times for transformation, but was not successfully transformed to the amorphous bulk; the same was observed for SA. It is suggested that the mutual existence of PX and SA promotes mutual amorphization.
Topics: Calorimetry, Differential Scanning; Piroxicam; Powder Diffraction; Powders; Saccharin; Solubility; Spectroscopy, Fourier Transform Infrared; Spectroscopy, Near-Infrared; X-Ray Diffraction
PubMed: 34139260
DOI: 10.1016/j.xphs.2021.06.024 -
Biomolecules Aug 2017Human insulin (HI) is a well-characterized natural hormone which regulates glycose levels into the blood-stream and is widely used for diabetes treatment. Numerous... (Review)
Review
Human insulin (HI) is a well-characterized natural hormone which regulates glycose levels into the blood-stream and is widely used for diabetes treatment. Numerous studies have manifested that despite significant efforts devoted to structural characterization of this molecule and its complexes with organic compounds (ligands), there is still a rich diagram of phase transitions and novel crystalline forms to be discovered. Towards the improvement of drug delivery, identification of new insulin polymorphs from polycrystalline samples, simulating the commercially available drugs, is feasible today via macromolecular X-ray powder diffraction (XRPD). This approach has been developed, and is considered as a respectable method, which can be employed in biosciences for various purposes, such as observing phase transitions and characterizing bulk pharmaceuticals. An overview of the structural studies on human insulin complexes performed over the past decade employing both synchrotron and laboratory sources for XRPD measurements, is reported herein. This review aims to assemble all of the recent advances in the diabetes treatment field in terms of drug formulation, verifying in parallel the efficiency and applicability of protein XRPD for quick and accurate preliminary structural characterization in the large scale.
Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin; Phenols; Powder Diffraction; Structure-Activity Relationship; X-Ray Diffraction
PubMed: 28829407
DOI: 10.3390/biom7030063 -
Acta Crystallographica Section B,... Jun 2022Experimental and computational studies of ammonium carbamate have been carried out, with the objective of studying the elastic anisotropy of the framework manifested in...
Ab initio simulations of α- and β-ammonium carbamate (NH·NHCO), and the thermal expansivity of deuterated α-ammonium carbamate from 4.2 to 180 K by neutron powder diffraction.
Experimental and computational studies of ammonium carbamate have been carried out, with the objective of studying the elastic anisotropy of the framework manifested in (i) the thermal expansion and (ii) the compressibility; furthermore, the relative thermodynamic stability of the two known polymorphs has been evaluated computationally. Using high-resolution neutron powder diffraction data, the crystal structure of α-ammonium carbamate (ND·NDCO) has been refined [space group Pbca, Z = 8, with a = 17.05189 (15), b = 6.43531 (7), c = 6.68093 (7) Å and V = 733.126 (9) Å at 4.2 K] and the thermal expansivity of α-ammonium carbamate has been measured over the temperature range 4.2-180 K. The expansivity shows a high degree of anisotropy, with the b axis most expandable. The ab initio computational studies were carried out on the α- and β-polymorphs of ammonium carbamate using density functional theory. Fitting equations of state to the P(V) points of the simulations (run athermally) gave the following values: V = 744 (2) Å and bulk modulus K = 16.5 (4) GPa for the α-polymorph, and V = 713.6 (5) Å and K = 24.4 (4) GPa for the β-polymorph. The simulations show good agreement with the thermoelastic behaviour of α-ammonium carbamate. Both phases show a high-degree of anisotropy; in particular, α-ammonium carbamate shows unusual compressive behaviour, being determined to have negative linear compressibility (NLC) along its a axis above 5 GPa. The thermodynamically stable phase at ambient pressure is the α-polymorph, with a calculated enthalpy difference with respect to the β-polymorph of 0.399 kJ mol; a transition to the β-polymorph could occur at ∼0.4 GPa.
Topics: Carbamates; Carbon Dioxide; Neutrons; Powder Diffraction; Powders
PubMed: 35702963
DOI: 10.1107/S2052520622002645 -
Talanta Apr 2019A considerable number of fatal intoxications have recently been connected with the growing popularity of new psychoactive substances (NPS). Therefore, there is a...
A considerable number of fatal intoxications have recently been connected with the growing popularity of new psychoactive substances (NPS). Therefore, there is a significant demand for the development of fast and facile field detection methods for NPS. These substances are often sold as blends (with inorganic or organic cutting agents), which may further complicate detection. X-Ray powder diffraction (XRPD) was evaluated as a suitable and easily employable analytical method for the identification of NPS. XRPD has been successfully used for the differentiation of eight synthetic cathinones with a similar molecular structure. Moreover, this method was also used for the identification of four drugs in authentic street samples. XRPD is a facile non-destructive method that can identify not only NPS in mixtures but also the cutting agents. The small amount of substances needed for the measurement, which can be re-used for other analyses, further enhances the versatility of this method.
Topics: Alkaloids; Central Nervous System Stimulants; Powder Diffraction; Psychotropic Drugs; X-Ray Diffraction
PubMed: 30625563
DOI: 10.1016/j.talanta.2018.11.063 -
ACS Applied Materials & Interfaces Apr 2021Breathomics is a widely emerging tool for noninvasive disease diagnosis and focuses on the detection of various levels of volatile organic compounds and inorganic gases...
Breathomics is a widely emerging tool for noninvasive disease diagnosis and focuses on the detection of various levels of volatile organic compounds and inorganic gases present in human breath. One of the rapid, easy-to-use, and noninvasive detection methods being investigated is a system that can measure exhaled breath ammonia levels and can be correlated to the functional state of protein metabolic pathways and the renal functioning system. In this work, we have demonstrated the development of an electrochemical nose system using ferrocene encapsulated into zeolitic imidazole framework, Fc@ZIF-8, which can be successfully used for the detection of ammonia levels in breath. This is the first report of an electrochemical gas sensor platform that uses a faradaic probe (that is ferrocene) encapsulated into a metal-organic framework cavity used for disease diagnosis by monitoring the levels of the target gas and can be used for breathomics applications. This work demonstrates that low levels of ammonia gas (up to 400 ppb) can be detected with high sensitivity and specificity. The morphological and structural characterization of the novel, synthesized Fc@ZIF-8 nanocomposite has been performed using powder X-ray diffraction, field emission scanning electron microscopy, Fourier transform infrared, ultraviolet-visible spectroscopy, and dynamic light scattering. Electrochemical characterization of the material has been performed using a standard glassy carbon electrode, and further application of the material has been shown using the in-house designed and reported spiral electrochemical notification coupled electrode, used for ammonia gas sensing. Cross-reactivity studies have also been performed to demonstrate sensor specificity toward the target gas. We demonstrate the first of its kind electrochemical bifunctional probe platform that can be used for sensing ammonia levels in breath, with high sensitivity and specificity, due to the hybrid material system-zinc-imidazole framework 8 (having excellent physisorption properties) and ferrocene (acting as a redox mediator). We envision that such a sensing system will allow noninvasive and early diagnosis of chronic kidney disease, thus leading to early treatment and a decrease in the mortality rate.
Topics: Ammonia; Breath Tests; Electrochemical Techniques; Electronic Nose; Metal-Organic Frameworks; Microscopy, Electron, Scanning; Powder Diffraction; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis
PubMed: 33792285
DOI: 10.1021/acsami.1c02283 -
Acta Crystallographica Section B,... Apr 2022A method of ab initio crystal structure determination from powder diffraction data for organic and metal-organic compounds, which does not require prior indexing of the...
A method of ab initio crystal structure determination from powder diffraction data for organic and metal-organic compounds, which does not require prior indexing of the powder pattern, has been developed. Only a reasonable molecular geometry is required, needing knowledge of neither unit-cell parameters nor space group. The structures are solved from scratch by a global fit to the powder data using the new program FIDEL-GO (`FIt with DEviating Lattice parameters - Global Optimization'). FIDEL-GO uses a similarity measure based on cross-correlation functions, which allows the comparison of simulated and experimental powder data even if the unit-cell parameters deviate strongly. The optimization starts from large sets of random structures in various space groups. The unit-cell parameters, molecular position and orientation, and selected internal degrees of freedom are fitted simultaneously to the powder pattern. The optimization proceeds in an elaborate multi-step procedure with built-in clustering of duplicate structures and iterative adaptation of parameter ranges. The best structures are selected for an automatic Rietveld refinement. Finally, a user-controlled Rietveld refinement is performed. The procedure aims for the analysis of a wide range of `problematic' powder patterns, in particular powders of low crystallinity. The method can also be used for the clustering and screening of a large number of possible structure candidates and other application scenarios. Examples are presented for structure determination from unindexed powder data of the previously unknown structures of the nanocrystalline phases of 4,11-difluoro-, 2,9-dichloro- and 2,9-dichloro-6,13-dihydro-quinacridone, which were solved from powder patterns with 14-20 peaks only, and of the coordination polymer dichloro-bis(pyridine-N)copper(II).
Topics: Copper; Polymers; Powder Diffraction; Powders
PubMed: 35411858
DOI: 10.1107/S2052520622001500 -
Pharmaceutical Development and... Dec 2018The objective of the present study was to investigate the influence of processing methods on the physical and mechanical properties of formulations containing Ibuprofen...
The objective of the present study was to investigate the influence of processing methods on the physical and mechanical properties of formulations containing Ibuprofen and HPC-SSL. The powder blends, containing Ibuprofen and HPC-SSL in ratio of 9:0.5, were processed using melt granulation (MG) by hot melt extrusion (HME) and wet granulation (WG) by high shear mixer. Formulated granules and powder blends were compressed into round flat faced tablets using Riva Piccola tablet press. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) studies proved that granulation process did not significantly alter the crystallinity of Ibuprofen, however, particle density and flow properties were significantly improved. Scanning electron microscopy (SEM) and particle size analysis corroborate with the findings that the flow characteristics of granules from MG were relatively superior to other formulations. Formulations were investigated for out-of-die compaction behaviour using Heckel, Kawakita, and CTC profile analysis. Detailed examination revealed that all three formulations differed in particle size due to the granulation, thus conferring to different compaction behaviour. In WG and MG, granulation offered an increase in particle size resulting in high compressibility along with deformation at low compression pressure. This results into low yield pressure, low yield strength, and higher densification, as compared with dry blend. The current work provides an insight into factors affecting physical and mechanical properties tablets, which can facilitate the rational selection of suitable change in processing method instead of changing excipients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Crystallization; Drug Compounding; Excipients; Ibuprofen; Particle Size; Powder Diffraction; Powders; Solubility; Tablets; X-Ray Diffraction
PubMed: 29310491
DOI: 10.1080/10837450.2018.1425430 -
Journal of Pharmaceutical Sciences Dec 2022Gefitinib (GEF) is an anti-tumor oral solid formulation with a superior advantage for lung tumors. However, it has poor aqueous solubility which limits its utility in...
Gefitinib (GEF) is an anti-tumor oral solid formulation with a superior advantage for lung tumors. However, it has poor aqueous solubility which limits its utility in vivo. Herein, a novel cocrystal (GEF-RES) assembled by GEF and RES (Resveratrol) has been successfully prepared and comprehensively characterized by differential scanning calorimetry, thermogravimetric analysis, Raman spectroscopy and powder X-ray diffraction. A single-crystal structure of the GEF-RES cocrystal was solved and illustrated in detail. In aqueous hydrochloric acid, the GEF-RES cocrystal showed that the maximum concentration of GEF was slightly higher than that of raw GEF. Furthermore, the thermal and physical stability of the GEF-RES cocrystal were also evaluated in this paper. The enhanced solubility and excellent solid-state stability results may provide new potential to the application of key GEF in clinical.
Topics: Solubility; Resveratrol; Gefitinib; Crystallization; Calorimetry, Differential Scanning; X-Ray Diffraction; Powder Diffraction
PubMed: 36202251
DOI: 10.1016/j.xphs.2022.09.031 -
International Journal of Pharmaceutics Jul 2019Commonly, a limited number of generally accepted bulking agents and lyoprotectants are used for freeze-drying; predominantly mannitol, glycine, sucrose and trehalose....
Commonly, a limited number of generally accepted bulking agents and lyoprotectants are used for freeze-drying; predominantly mannitol, glycine, sucrose and trehalose. The purpose of this study was to combine a theoretical approach using molecular descriptors with a large scale experimental screening to evaluate the suitability of a broad range of excipients for freeze-drying. A large selection of sugars, polyols and amino acids was characterized by modulated differential scanning calorimetry (mDSC) and X-ray powder diffraction (XRPD) after well-plate based freeze-drying. The calculated molecular descriptors were investigated with both hierarchical cluster analysis and principal component analysis. A clear clustering of the excipients according to the size-related and weight-related descriptors was observed; however other relevant descriptors could also be identified. From a practical perspective, a trend was observed with regard to a higher likelihood for amorphisation and a higher glass transition temperature of the maximally freeze-concentrated solution with increasing molecular size. A translation of the molecular descriptors on pharmaceutical performance was more successful for lyoprotectants than for bulking agents. Additionally, in the course of the experimental screening, several new potential bulking agents and lyoprotectants were identified.
Topics: Calorimetry, Differential Scanning; Excipients; Freeze Drying; Glycine; Mannitol; Powder Diffraction; Sucrose; Trehalose; X-Ray Diffraction
PubMed: 31145963
DOI: 10.1016/j.ijpharm.2019.05.065 -
Journal of Pharmaceutical Sciences Jul 2018The present study reports a high-throughput screening method for the salt formation of amine-containing active pharmaceutical ingredients (APIs) based on fluorescence...
The present study reports a high-throughput screening method for the salt formation of amine-containing active pharmaceutical ingredients (APIs) based on fluorescence measurements. A free form amine API was alkynylated by a solid-vapor reaction using propargyl bromide, and a fluorescent compound was produced by a subsequent reaction using 9-azidomethylanthracene. In contrast, salts were inert to propargyl bromide; thus, no fluorescence was observed. Samples for salt screening were prepared by grinding haloperidol with various counter acids, and these mixtures were derivatized in a 96-well microplate to determine whether the salt formation had occurred between haloperidol and the counter acids. Samples that turned into fluorescent and nonfluorescent were confirmed to be free form and salt form, respectively, using powder X-ray diffraction and Raman spectroscopy. In conclusion, our method adequately functions as an indicator of the salt formation of amine APIs. Further, this method allows for the rapid evaluation of the salt formation of APIs using 96-well microplates without the need for special reagents or techniques; thus, it is valuable for the discovery of an optimal salt form of newly developed amine APIs in the pharmaceutical industry.
Topics: Amines; Pharmaceutical Preparations; Powder Diffraction; Salts; Spectrometry, Fluorescence; Spectrum Analysis, Raman; X-Ray Diffraction
PubMed: 29499276
DOI: 10.1016/j.xphs.2018.02.018