Solvates of the antifungal drug griseofulvin: structural, thermochemical and conformational analysis

2013 ◽  
Vol 70 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Srinivasulu Aitipamula ◽  
Pui Shan Chow ◽  
Reginald B. H. Tan
Keyword(s):  
Melting Point ◽  
Solvent Free ◽  
Antifungal Drug ◽  
Free Form ◽  
Solution Stability ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Solvent Molecules ◽  
Solid Form

Four solvates of an antifungal drug, griseofulvin (GF), were discovered. All the solvates were characterized by differential scanning calorimetry, thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The solvents that form the solvates are acetonitrile, nitromethane and nitroethane (2:1 and 1:1). It was found that all the solvates lose the solvent molecules from the crystal lattice between 343 and 383 K, and that the melting point of the desolvated materials matched the melting point of the solvent-free GF (493 K). The conformation of the GF molecule in solvent-free form was found to be significantly different from the conformations found in the solvates. Solution stability studies revealed that the GF–acetonitrile solvate transforms to GF and that GF–nitroethane (1:1) solvate transforms to GF–nitroethane (2:1) solvate. On the other hand, GF–nitromethane and GF–nitroethane (2:1) solvates were found to be stable in solution. Our results highlight the importance of the co-crystallization technique in the pharmaceutical drug development; it not only expands the solid form diversity but also creates new avenues for unraveling novel solvates.

scholarly journals Formation of Pharmaceutical Salts and Cocrystals via Vapour-Assisted Tumbling (VAT) – A Solvent Efficient Process with Potential Industrial Applications

2021 ◽  
Author(s):  
Alexander J. Stirk ◽  
Fabio E. S. Souza ◽  
Jenny Gerster ◽  
Fatemeh M. Mir ◽  
Avedis Karadeolian ◽  
...  
Keyword(s):  
Differential Scanning Calorimetry ◽  
Environmental Impact ◽  
Industrial Applications ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
New Techniques ◽  
X Ray ◽  
Industry Standard ◽  
Pharmaceutical Salts ◽  
Solid Form

Crystallisations on both the academic and industrial scale often use large volumes of solvent. In order decrease the environmental impact of such processes, new techniques must be discovered that increase the efficiency of the solvents used. Introduced here is a process that combines repurposed industry standard hardware and aspects of mechanochemistry to produce a technique we call “Vapour Assisted Tumbling” (VAT). Pharmaceutical and well-known cocrystals and salts were formed by tumbling the coformers in an atmosphere of vaporised solvent, in this study, methanol (MeOH). This was done inside a custom built analogue of an industrial rotary cone dryer (RCD). It was found that a desired solid form could be obtained as monitored by powder X-ray diffraction and differential scanning calorimetry. By repurposing industrial RCDs, it is feasible that solid forms can be crystallised with both minimal and reusable/recyclable solvent – drastically lowering the environmental impact of such transformations.

scholarly journals The Usefulness of X-ray Diffraction and Thermal Analysis to Study Dietary Supplements Containing Iron

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 197
Author(s):  
Izabela Jendrzejewska ◽  
Robert Musioł ◽  
Tomasz Goryczka ◽  
Ewa Pietrasik ◽  
Joanna Klimontko ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Melting Point ◽  
Dietary Supplements ◽  
Polymorphic Form ◽  
Food Supplements ◽  
X Ray Diffraction ◽  
Iron Compounds ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Amorphous Compounds

X-ray powder diffraction (XRPD) and thermal analysis (differential scanning calorimetry/derivative of thermogravimetry (DSC/DTG)) are solid-state techniques that can be successfully used to identify and quantify various chemical compounds in polycrystalline mixtures, such as dietary supplements or drugs. In this work, 31 dietary supplements available on the Polish market that contain iron compounds, namely iron gluconate, fumarate, bisglycinate, citrate and pyrophosphate, were evaluated. The aim of the work was to identify iron compounds declared by the manufacturer as food supplements and to try to verify compliance with the manufacturer’s claims. Studies performed by X-ray and thermal analysis confirmed that crystalline iron compounds (iron (II) gluconate, iron (II) fumarate), declared by the manufacturers, were present in the investigated dietary supplements. Iron (II) bisglycinate proved to be semi-crystalline. However, depending on the composition of the formulation, it was possible to identify this compound in the tested supplements. For amorphous iron compounds (iron (III) citrate and iron (III) pyrophosphate), the diffraction pattern does not have characteristic diffraction lines. Food supplements containing crystalline iron compounds have a melting point close to the melting point of pure iron compounds. The presence of excipients was found to affect the shapes and positions of the endothermic peaks significantly. Widening of endothermic peaks and changes in their position were observed, as well as exothermic peaks indicating crystallization of amorphous compounds. Weight loss was determined for all dietary supplements tested. Analysis of the DTG curves showed that the thermal decomposition of most food supplements takes place in several steps. The results obtained by a combination of both simple, relatively fast and reliable XRPD and DSC/DTG methods are helpful in determining phase composition, pharmaceutical abnormalities or by detecting the presence of the correct polymorphic form.

scholarly journals Evaluation of Thermal-Induced Polymorphic Transformation on Desloratadine and Desloratadine-Benzoic Acid Salt

2020 ◽  
Vol 26 (4) ◽  
pp. 399-405
Author(s):  
Ahmad Ainurofiq ◽  
Rachmat Mauludin ◽  
Diky Mudhakir ◽  
Sundani Nurono Soewandhi
Keyword(s):  
Melting Point ◽  
Benzoic Acid ◽  
Polymorphic Transformation ◽  
Heating Process ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Physicochemical Changes ◽  
Transformation Methods

Background: Active pharmaceutical ingredients face a challenge in manufacturing due to adverse physicomechanical properties. Desloratadine (DES) form I exhibits poor mechanical behavior through the formation of capping during the tableting process. Salt formation from DES and benzoic acid (BA) has been observed to resolve poor mechanical properties. However, the ability to withstand heat from the manufacturing process should be implemented in DES and DES-BA salt. The aim of this study was to determine the differences between thermal treatment results on DES and DES-BA salt and whether it causes them to undergo polymorphic transformation. Methods: Salt was crystallized between DES and BA using the solvent evaporation method. DES and DES-BA salt were heated at 110°C, 159°C (melting point of DES), 181°C (melting point of DES-BA), and 190°C. Following this, characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and solubility testing. Results: Polymorphic transformation caused by heat occurred in DES, but not in DES-BA salt. The transformation of DES was induced by the effect of heating, which changed polymorph I to a mixture of polymorph I and III at 110°C, to polymorph II at 159°C, and to a mixture of polymorph I, II, and III at 190°C. Under 190oC, DES-BA is still stable and did not undergo a polymorphic transformation. However, at 190oC, decomposition started to occur, which implied decreased solubility, which did not occur in DES. Conclusion: The heating process did not cause DES-BA salt to undergo a polymorphic transformation. However, it caused decomposition at 190oC. DES underwent a polymorphic transformation when exposed to the same condition without decomposition. This provided information to always pay attention to temperature during manufacturing processes that include DES or DES-BA salt to avoid physicochemical changes.

scholarly journals Crystal Structure, Stability and Desolvation of the Solvates of Sorafenib Tosylate

Crystals ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 367 ◽  
Author(s):  
Peng Yang ◽  
Chunlei Qin ◽  
Shichao Du ◽  
Lina Jia ◽  
Yujia Qin ◽  
...  
Keyword(s):  
Polarized Light ◽  
Vital Role ◽  
Structure Stability ◽  
X Ray Diffraction ◽  
Hydrogen Bond Donor ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Ethanol Solvate ◽  
Donor Acceptor ◽  
Solvent Molecules

In this study, three solvates of sorafenib tosylate were obtained from methanol, ethanol and n-methyl-2-pyrrolidone (NMP) after solvate screening and the effect of solvent on the formation of solvate was analyzed. The solvents with high value of polarity/dipolarity and appropriate hydrogen bond donor/acceptor propensity are more likely to form corresponding solvates. The crystal structures of the solvates were elucidated for the first time by using single crystal X-ray diffraction data. The analysis results indicate that methanol solvate and ethanol solvate are isostructural and hydrogen bonds could be formed between solvent molecules and sorafenib tosylate molecules. Hirshfeld surface analysis was used to research the interactions in the solvates, and the results reveal that the H···H, C···H/H···C and O···H/ H···O contacts play the vital role in molecular packing. In addition, three solvates were characterized by polarized light microscope, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The solvates show different thermodynamic stability in methanol +NMP and ethanol +NMP mixtures. Furthermore, the desolvation of solvates was studied by hot stage microscope and discussed.

scholarly journals Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals

2021 ◽  
Vol 22 (2) ◽  
pp. 928
Author(s):  
Muhammad Inam ◽  
Lu Liu ◽  
Jian-Wei Wang ◽  
Ka-Xi Yu ◽  
Chi-Uyen Phan ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Kidney ◽  
Drug Formulation ◽  
Free Form ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Hek 293 ◽  
X Ray ◽  
Glucose Levels ◽  
Two Phases

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.

scholarly journals Multi-Component Crystals of 2,2′-Bipyridine with Aliphatic Dicarboxylic Acids: Melting Point-Structure Relations

Crystals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1151
Author(s):  
Vhukhudo Nethanani ◽  
Eustina Batisai
Keyword(s):  
Melting Point ◽  
Dicarboxylic Acids ◽  
Conformation Analysis ◽  
Solvent Evaporation Method ◽  
X Ray Diffraction ◽  
Melting Points ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Aliphatic Dicarboxylic Acids ◽  
The Relationship

The aim of the study was to investigate the relationship between the melting point and the supramolecular structure of three multi-component crystals of aliphatic dicarboxylic acids with 2,2′-bipyridine and to investigate the conformations of 2,2′-bipyridine in published multi-component crystals. The crystals were prepared using the solvent evaporation method and were characterized using single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The crystal structures were further analyzed using CrystalExplorer, and the results were correlated with the melting points. The results of the conformation analysis of the reported multi-component crystals of 2,2′-bipyridine are also presented.

Diversity of N-triphenylacetyl-L-tyrosine solvates with halogenated solvents

2021 ◽  
Vol 77 (12) ◽  
Author(s):  
Agnieszka Czapik ◽  
Marcin Kwit
Keyword(s):  
Hydrogen Bonds ◽  
Crystal Structures ◽  
Free Form ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Intermolecular Hydrogen Bonds ◽  
Guest Molecules ◽  
Sterically Demanding ◽  
Halogenated Solvents ◽  
Solvent Molecules

The structure of N-triphenylacetyl-L-tyrosine (C29H25NO4, L-TrCOTyr) is characterized by the presence of both donors and acceptors of classical hydrogen bonds. At the same time, the molecule contains a sterically demanding and hydrophobic trityl group capable of participating in π-electron interactions. Due to its large volume, the trityl group may favour the formation of structural voids in the crystals, which can be filled with guest molecules. In this article, we present the crystal structures of a series of N-triphenylacetyl-L-tyrosine solvates with chloroform, namely, L-TrCOTyr·CHCl3 (I) and L-TrCOTyr·1.5CHCl3 (III), and dichloromethane, namely, L-TrCOTyr·CH2Cl2 (II) and L-TrCOTyr·0.1CH2Cl2 (IV). To complement the topic, we also decided to use the racemic amide N-triphenylacetyl-DL-tyrosine (rac-TrCOTyr) and recrystallized it from a mixture of chloroform and dichloromethane. As a result, rac-TrCOTyr·1.5CHCl3 (V) was obtained. In the crystal structures, the amide molecules interact with each other via O—H...O hydrogen bonds. Noticeably, the amide N—H group does not participate in the formation of intermolecular hydrogen bonds. Channels are formed between the TrCOTyr molecules and these are filled with solvent molecules. Additionally, in the crystals of III and V, there are structural voids that are occupied by chloroform molecules. Structure analysis has shown that solvates I and II are isostructural. Upon loss of solvent, the solvates transform into the solvent-free form of TrCOTyr, as confirmed by thermogravimetric analysis, differential scanning calorimetry and powder X-ray diffraction.

scholarly journals Pharmaceutical Solid Form Formation via Vapour-Assisted Tumbling (VAT) – A Solvent Efficient Process with Potential Industrial Applications

2021 ◽  
Author(s):  
Alexander Joseph Stirk ◽  
Fabio E. S. Souza ◽  
Jenny Gerster ◽  
Fatemeh M. Mir ◽  
Avedis Karadeolian ◽  
...  
Keyword(s):  
Differential Scanning Calorimetry ◽  
Environmental Impact ◽  
Industrial Applications ◽  
Industrial Scale ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
New Techniques ◽  
X Ray ◽  
Industry Standard ◽  
Solid Form

Crystallisations on both the academic and industrial scale often use large volumes of solvent. In order decrease the environmental impact of such processes, new techniques must be discovered that increase the efficiency of the solvents used. Introduced here is a process that combines repurposed industry standard hardware and aspects of mechanochemistry to produce a technique we call “Vapour Assisted Tumbling” (VAT). Pharmaceutical and well-known cocrystals and salts were formed by tumbling the coformers in an atmosphere of vaporised solvent, in this study, methanol (MeOH). This was done inside a custom built analogue of an industrial rotary cone dryer (RCD). It was found that a desired solid form could be obtained as monitored by powder X-ray diffraction and differential scanning calorimetry. By repurposing industrial RCDs, it is feasible that solid forms can be crystallised with both minimal and reusable/recyclable solvent – drastically lowering the environmental impact of such transformations.

scholarly journals Pengaruh Faktor Geografi Terhadap Karakteristik Bambu Petung

2019 ◽  
Vol 3 (1) ◽  
pp. 25-32
Author(s):  
Andromeda Dwi Laksono ◽  
Diah Tri Agustiningtyas
Keyword(s):  
Melting Point ◽  
Energy Dispersive Spectrometer ◽  
The Philippines ◽  
Phase Changes ◽  
Cubic Phase ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Peak Value

In this study was about a comparison of geographic factors towards the characterization of petung bamboo in Indonesia and the Philippines. Bamboo is one of the plants that has advantages in the field of technical materials based on developments in composite materials and is found in various regions. In general, bamboo has lignin and cellulose, where the morphology and nature of both bamboos are not the same from different countries. Therefore,material testing was carried out on each Indonesian and Filipino petung bamboo using material characterization testing methods. The process of Differential Scanning Calorimetry (DSC) was carried out to measure calorimetry with the yield of melting point in Philippine petung bamboo at 341ºC which is lower than the melting point in Indonesian petung bamboo which is 354.34ºC. In this DSC test, quantitative and qualitative results were obtainedin the form of phase changes, melting, and transition temperatures that occurred. Then an Energy Dispersive Spectrometer (EDS) was analyzed and the carbon content of cellulose and lignin was higher in Indonesian petung bamboo, respectively 65.29 wt.% And 66.05 wt.%. The morphology of bamboo shows that the fibers and matrices present in Philippine petung bamboo are denser than those of Indonesian petung bamboo. The highest peak value based on X-Ray Diffraction (XRD) is found in Philippine petung bamboo at 2ș of 34.49 and cubic phase.

scholarly journals Study of possibility physical interactions antimalarial combination drugs

2020 ◽  
Author(s):  
Timbul Partogi H. Simorangkir
Keyword(s):  
Phase Diagram ◽  
Solid State ◽  
Melting Point ◽  
Crystal Habit ◽  
Supersaturated Solution ◽  
Physical Interaction ◽  
Contact Method ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray

Identification of solid state to investigate the possibility of physical interaction between Antimalarial Artemisinin Combination Treatment base Artesunate (AS) and Amodiaquine (AQ) by hot contact method Kofler, cold contact method (crystallization reaction) and binary phase diagram confirmation had been carried out. The results of hot contact method Kofler shown the formation a new crystalline habit as a long and thin needle on the contact zone (mixing zone) between AS and AQ. A different melting point was seen in its single component. Cold contact methods between two of supersaturated solution of component AS and AQ in methanol solvent also indicated the growth of crystal habit as similar as hot contact method Kofler. Confirmation by biner phase diagram shown the specific diagram for cocrystalline phase. Solid state interaction between AS and AQ was analysed by powder X-ray diffraction, FTIR (Fourier Transformed Infra Red) spectrophotometric, microscopic SEM (Scanning Electron Microscopic) and thermal DTA (Differential Thermal Analysis), TG-DSC (Thermal Gravimetry- Differential Scanning Calorimetry). Microscopic analysis by SEM showed significantly the change of habit and morphology of crystal to long and thin needle shaped. The difference of powder X-ray diffraction (PXRD) interferences peaks were observed in addition to PXRD interference peaks of each component and its physical mixtures that proved formation of cocrystalline phase. DSC Thermogram indicated a new endothermic peak corresponding to melting point of a new cocrystalline phase at temperature 160,4°C.

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