Chemical and physical modification of hemp fibres by steam explosion technology
In current research attempt has been made to analyse hemp fibres treated with steam explosion (SE) technology. Disintegration of hemp fibres separated from non-retted, dew-retted and dried stems of hemp ('Purini')[1] by alkali treatment and steam explosion (SE) were investigated. An average intensive SE in combination with the hydro-thermal and alkali after-treatment allows decreasing the diameter of hemp fibres and reduce the concentration of non-celluloses components, among them hemicelluloses, lignin, pectin, waxes and water [1;2].
Combined Use of Structure Analysis, Studies of Molecular Association in Solution, and Molecular Modelling to Understand the Different Propensities of Dihydroxybenzoic Acids to Form Solid Phases
The arrangement of hydroxyl groups in the benzene ring has a significant effect on the propensity of dihydroxybenzoic acids (diOHBAs) to form different solid phases when crystallized from solution. All six diOHBAs were categorized into distinctive groups according to the solid phases obtained when crystallized from selected solvents. A combined study using crystal structure and molecule electrostatic potential surface analysis, as well as an exploration of molecular association in solution using spectroscopic methods and molecular dynamics simulations were used to determine the possible mechanism of how the location of the phenolic hydroxyl groups affect the diversity of solid phases formed…
On the Formation and Desolvation Mechanism of Organic Molecule Solvates: A Structural Study of Methyl Cholate Solvates
Solvate formation and the desolvation mechanism of 25 obtained methyl cholate solvates were rationalized using crystal structure analysis and study of the phase transformations. The facile solvate formation was determined to be associated with the possibility for more efficient packing in structures containing solvent molecules. Most of the obtained solvates crystallized in one of the six isostructural solvate groups, with solvent selection based on the solvent capability to provide particular intermolecular interactions along with appropriate size and shape. In crystal structures several different methyl cholate conformers were observed, as apparently more efficient packing could be achiev…
On the Formation of Droperidol Solvates: Characterization of Structure and Properties
A solvate screening and characterization of the obtained solvates was performed to rationalize and understand the solvate formation of active pharamaceutical ingredient droperidol. The solvate screening revealed that droperidol can form 11 different solvates. The analysis of the crystal structures and molecular properties revealed that droperidol solvate formation is mainly driven by the inability of droperidol molecules to pack efficiently. The obtained droperidol solvates were characterized by X-ray diffraction and thermal analysis. It was found that droperidol forms seven nonstoichiometric isostructural solvates, and the crystal structures were determined for five of these solvates. To b…
Solid Solutions in the Xanthone–Thioxanthone Binary System: How Well Are Similar Molecules Discriminated in the Solid State?
The binary system of xanthone–thioxanthone has been explored, showing that two solid solutions (formed based on xanthone and thioxanthone parent structures, respectively) exist for this system. One...
Synthesis of Nanofibrillated Cellulose by Combined Ammonium Persulphate Treatment with Ultrasound and Mechanical Processing
Ammonium persulfate has been known as an agent for obtaining nanocellulose in recent years, however most research has focused on producing cellulose nanocrystals. A lack of research about combined ammonium persulfate oxidation and common mechanical treatment in order to obtain cellulose nanofibrils has been identified. The objective of this research was to obtain and investigate carboxylated cellulose nanofibrils produced by ammonium persulfate oxidation combined with ultrasonic and mechanical treatment. Light microscopy, atomic force microscopy (AFM), powder X-Ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and Zeta potential measure…
Comparison and Rationalization of Droperidol Isostructural Solvate Stability: An Experimental and Computational Study
In order to find a tool for comparison of solvate stability and to rationalize their relative stability, droperidol nonstoichiometric isostructural solvates were characterized experimentally and computationally. For the experimental evaluation of stability, three comparison tools were considered: thermal stability characterized by the desolvation rate, desolvation activation energy, and solvent sorption–desorption isotherms. It was found that the desolvation process was limited by diffusion, and the same activation energy values were obtained for all of the characterized solvates, while the solvent content in the sorption isotherm was determined by the steric factors. Therefore, the only cr…
On the Rationalization of Formation of Solvates: Experimental and Computational Study of Solid Forms of Several Nitrobenzoic Acid Derivatives
Analysis of crystal structures, molecular properties, interaction strength in solution and computationally generated non-solvated form solid form landscapes of five chloronitrobenzoic acid isomers ...
Why Do Chemically Similar Pharmaceutical Molecules Crystallize in Different Structures: A Case of Droperidol and Benperidol
A detailed study of molecular conformation and intermolecular interactions in the experimental crystal structures and general trends observed in the Cambridge Structural Database as well as theoretical calculations were performed to identify the reason for the formation of different crystal structures of two chemically very similar pharmaceutical molecules benperidol and droperidol. The most important difference between both molecules was the weak intermolecular interactions formed by the central ring which therefore was responsible for the formation of different crystal structures. Cross-seeding experiments were performed to check the possibility for the formation of mutually isostructural…
Dehydration of mildronate dihydrate: a study of structural transformations and kinetics
The dehydration of mildronate dihydrate (3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propionate dihydrate) was investigated by powder X-ray diffraction, thermal analysis, hot-stage microscopy, water sorption–desorption studies and dehydration kinetic studies. It was determined that mildronate dihydrate dehydrated in a single step, directly transforming into the anhydrous form. In order to understand the reasons for a one step dehydration mechanism, crystal structures of dihydrate, monohydrate and anhydrous forms were compared, proving the similarity of the dihydrate and anhydrous forms. In order to understand the reasons for molecule reorganization during dehydration, the energy of the anhydrous …
Structure and Stability of Racemic and Enantiopure Pimobendan Monohydrates: On the Phenomenon of Unusually High Stability
Study of structures and physicochemical properties of racemic (rac-H) and enantiopure (enant-H) hydrates of the active pharmaceutical ingredient pimobendan revealed that both hydrates have highly similar crystal structures and exhibit unusually high stability. Both structures contain identical two-dimensional layers and very similar conformations. The most significant difference is the stacking of these layers. The high stability of both hydrates appeared as extremely low solubility over a wide temperature range as well as an exceptionally high dehydration temperature and melting point. Study of the dehydration process showed that both hydrates have different activation energies of dehydrat…
Single Enantiomer’s Urge to Crystallize in Centrosymmetric Space Groups: Solid Solutions of Phenylpiracetam
A detailed thermochemical and structural study of the phenylpiracetam enantiomer system was performed by characterizing the solid solutions, rationalizing the structural driving force for their formation, as well as identifying a common structural origin responsible for the formation of solid solutions of enantiomers. Enantiomerically pure phenylpiracetam forms two enantiotropically related polymorphs (enant–A and enant–B). The transition point (70(7) °C) was determined based on isobaric heat capacity measurements. Structural studies revealed that enant–A and enant–B crystallize in space groups P1 (Z′ = 4) and P212121 (Z′ = 2), respectively. However, pseudoinversion centers were present res…
Polymorphs and Hydrates of Sequifenadine Hydrochloride: Crystallographic Explanation of Observed Phase Transitions and Thermodynamic Stability
In this study, detailed analysis of crystal structures was used to rationalize the observed stability and phase transformations of sequifenadine hydrochloride polymorphs and hydrates, as well as to understand the observed structural diversity. The performed polymorph and hydrate screening revealed the existence of six polymorphs and four hydrates. Crystal structures of these phases were determined either from single crystal or from powder diffraction data. The different possibilities for packing of sequifenadine cations were found to be the main reason for the observed structural diversity of polymorphs. The hydrate structures were found to be structurally similar and related to those of pa…
Hexamorphism of Dantrolene: Insight into the Crystal Structures, Stability, and Phase Transformations
Dantrolene represents yet another interesting example of abundant molecular crystal polymorphism existing in at least six different neat polymorphs, three of which can be obtained via crystallizati...
Three anhydrous forms and a dihydrate form of quifenadine hydrochloride: a structural study of the thermodynamic stability and dehydration mechanism
Crystal structures of dihydrate (DH) and three anhydrous forms (A, B and C) of quifenadine (1-azabicyclo[2.2.2]oct-8-yl-diphenyl-methanol) hydrochloride are presented, and crystal structure information is used to explain and rationalize the relative stability of polymorphs and observed phase transformations. The dehydration mechanism of the hydrate is provided by interpreting the results obtained in studies of crystal structures, dehydration kinetics and thermal analysis. Structural analysis is used to explain the observed relative stability of the anhydrous phases and the hydrate. The crystal structures have been determined either from single crystal (form DH) or from powder diffraction da…
Hydration and dehydration kinetics of xylazine hydrochloride
From the experiments where mixture of xylazine hydrochloride hydrate H and anhydrous X were held at constant conditions, the stable form of xylazine hydrochloride can be found out. To determine equilibrium relative humidity, the unstable form of xylazine hydrochloride was inserted in thermostated humidity chamber and its weight was recorded by weighing the sample outside the chamber. The kinetic model and the rate constant for each condition were determined. The rate constants give information regarding the speed of the process at every experimentally used relative humidity. Thus using the data in coordinates k – p for each temperature it is possible to determine the water vapor pressure of…
Structural Characterization and Rationalization of Formation, Stability, and Transformations of Benperidol Solvates
Experimental and theoretical characterization and studies of phase transitions and stability of the solvates obtained in solvate screening of the pharmaceutical compound benperidol were performed to rationalize and understand the solvate formation, stability, and phase transitions occurring during their desolvation. The solvate screening revealed that benperidol can form 11 solvates, including two sets of isostructural solvates. The analysis of the solvate crystal structures and molecular properties indicated that benperidol solvate formation is mainly driven by the complications during packing of benperidol molecules in an energetically efficient way in the absence of solvent molecules, as…
Solid-state NMR and computational investigation of solvent molecule arrangement and dynamics in isostructural solvates of droperidol.
(13)C, (15)N and (2)H solid-state NMR spectroscopy have been used to rationalize arrangement and dynamics of solvent molecules in a set of isostructural solvates of droperidol. The solvent molecules are determined to be dynamically disordered in the methanol and ethanol solvates, while they are ordered in the acetonitrile and nitromethane solvates. (2)H NMR spectra of deuterium-labelled samples allowed the characterization of the solvent molecule dynamics in the alcohol solvates and the non-stoichiometric hydrate. The likely motion of the alcohol molecules is rapid libration within a site, plus occasional exchange into an equivalent site related by the inversion symmetry, while the water mo…
Effect of Experimental and Sample Factors on Dehydration Kinetics of Mildronate Dihydrate: Mechanism of Dehydration and Determination of Kinetic Parameters
The dehydration kinetics of mildronate dihydrate [3-(1,1,1-trimethylhydrazin-1-ium-2-yl)propionate dihydrate] was analyzed in isothermal and nonisothermal modes. The particle size, sample preparation and storage, sample weight, nitrogen flow rate, relative humidity, and sample history were varied in order to evaluate the effect of these factors and to more accurately interpret the data obtained from such analysis. It was determined that comparable kinetic parameters can be obtained in both isothermal and nonisothermal mode. However, dehydration activation energy values obtained in nonisothermal mode showed variation with conversion degree because of different rate-limiting step energy at hi…
Formation and Transformations of Organic Salt Hydrates: Four Encenicline Hydrochloride Monohydrates and Respective Isostructural Desolvates
Encenicline hydrochloride (Enc-HCl) crystallizes in four different monohydrate phases, but at the same time crystallization in a nonsolvated phase is not observed, indicating that water plays a crucial role in guiding the crystallization process and ensuring structure stability. All monohydrate phases show exceptionally high stability, and the main structural motif stays intact even after dehydration, leading to isostructural (for I and II) or isomorphic (for III) desolvates. Three monohydrate phases with determined crystal structure information consists of Enc-HCl-water hexamers that are stacked into similar slabs, that are further packed identically in monohydrates I, II, and III. The fea…
On the structural aspects of solid solutions of enantiomers: an intriguing case study of enantiomer recognition in the solid state
Structural aspects of solid solutions of enantiomers have been considered and the corresponding definitions of type 1 and type 2 solid solutions have been revised based on the available structures reported in the literature. Examples of both types are presented indicating that (e.g., type 1 solid solutions) there is a straightforward relationship between the particular structural aspects and the enantiomer miscibility limits in the solid state. Furthermore, enantiomer recognition in a type 2 solid solution formed by the enantiomers of a pharmaceutically active ingredient, pimobendan, has been studied in more detail. It was found that upon rapid crystallization from a solution a structure po…
The relative stability of xylazine hydrochloride polymorphous forms
All four known xylazine hydrochloride polymorphous forms were obtained and their relative stabilities were compared directly at three different temperatures. At higher temperatures, it is possible to determine the relative stability of all forms directly by measuring the changes in the composition of the mixtures of two polymorphous forms using powder x-ray diffraction methods. At lower temperatures, a solvent was added to the mixture and the changes in composition were determined. Polymorph transition temperatures were determined directly. To predict the transition temperature which was not found using the direct method, the polymorph melting data and determined transition temperatures wer…
Evaluation of Aspects Controlling Crystallization of Nitrofurantoin
Nitrofurantoin was crystallized from multiple mixtures of water and organic solvents with and without additives to try to find and identify factors affecting phase obtained in crystallization and provide possible information on crystallization control. Obtained crystals were identified with powder X-ray diffractometry. Crystallization control possibilities were evaluated by using polymer additives and crystallization additives, by also using quantum chemical calculations to investigate the association of nitrofurantoin and additive molecules and calculate Gibbs energy of association.
Polymorphism of R-Encenicline Hydrochloride: Access to the Highest Number of Structurally Characterized Polymorphs Using Desolvation of Various Solvates
In a study of the solid form landscape of R-encenicline hydrochloride (Enc-HCl), it was found that this compound is dodecamorphic and presents the first published example of polymorphism with a rec...
Detailed Analysis of Packing Efficiency Allows Rationalization of Solvate Formation Propensity for Selected Structurally Similar Organic Molecules
In structural study of seven bile acids it was identified that their propensity for solvate formation is directly related to the packing efficiency of the unsolvated phases: low packing index, voids, and unsatisfied hydrogen bonding lead to extensive solvate formation, whereas efficient packing leads to the opposite. This was determined to be caused by the presence of OH group attached to carbon C12. Solvate formation was determined to provide a noticeable improvement in the packing efficiency for compounds having ansolvates with inefficient packing.
A Maze of Solid Solutions of Pimobendan Enantiomers: An Extraordinary Case of Polymorph and Solvate Diversity
Over 10 polymorphs and solvatomorphs of the chiral pharmaceutically active ingredient pimobendan were found to lack enantioselectivity in the solid state, accordingly, forming solid solutions of enantiomers, which is reported to be a rare phenomenon. Solid form screening was performed on different enantiomeric composition samples to analyze obtained phases with powder X-ray diffraction and thermogravimetric differential scanning calorimetry. For nonsolvated forms, a melt phase diagram has been constructed convincingly showing the existence of stable and metastable solid solutions near the pure enantiomer and around the racemic composition regions. A crystal structure study combined with sol…