Processing of Thin Films Based on Cellulose Nanocrystals and Biodegradable Polymers by Space-Confined Solvent Vapor Annealing and Morphological Characteristics.

L-poly(lactic acid), poly(3-hydroxybutyrate), and poly-hydroxybutyrate-co-hydroxyvalerate are biodegradable polymers that can be obtained from renewable biomass sources. The aim of this study was to develop three types of environmentally friendly film biocomposites of altered microstructure by combining each of the above-mentioned polymers with cellulose nanocrystal fillers and further processing the resulting materials via space-confined solvent vapor annealing. Cellulose was previously obtained from renewable biomass and further converted to cellulose nanocrystals by hydrolysis with the lactic acid. The solutions of biodegradable polymers were spin-coated onto solid substrates before and after the addition of cellulose nanocrystals. The obtained thin film composites were further processed via space-confined solvent vapor annealing to eventually favor their crystallization and, thus, to alter the final microstructure. Indeed, atomic force microscopy studies have revealed that the presence of cellulose nanocrystals within a biodegradable polymer matrix promoted the formation of large crystalline structures exhibiting fractal-, spherulitic- or needle-like morphologies.

Enhanced Stability of Dopamine Delivery via Hydrogel with Integrated Graphene.

The synthesis of graphene-based materials for drug delivery represents an area of active research, and the use of graphene in drug delivery systems is promising due to its unique properties. Thus, in the present work, we discuss the potential of few-layer graphene in a hydrogel system for dopamine release. The hydrogels are frequently used for these systems for their special physico-chemical properties, which can ensure that the drug is effectively released in time. However, the release from such structures is mostly determined by diffusion alone, and to overcome this restriction, the hydrogel can be "improved" with nanoscale fillers like graphene. The release kinetics of the composite obtained were analyzed to better understand how the use of graphene, instead of the more common graphene oxide (GO) and reduced graphene oxide (rGO), affects the characteristics of the system. Thus, the systems developed in this study consist of three main components: biopolymer, graphene, and dopamine. The hydrogels with graphene were prepared by combining two different solutions, one with polyacrylic acid and agarose and one with graphene prepared by the exfoliation method with microwave irradiation. The drug delivery systems were developed by adding dopamine to the obtained hydrogels. After 24 h of release, the presence of dopamine was observed, demonstrating that the system developed can slow down the drug's degradation because of the interactions with the graphene nanoplates and the polymer matrix.

Antioxidant, Anti-Inflammatory Effects and Ability to Stimulate Wound Healing of a Common-Plantain Extract in Alginate Gel Formulations.

Our study aimed to investigate the biological effects of a common-plantain (Plantago major L.) extract, encapsulated in alginate, on dermal human fibroblast cultures in vitro, in view of its potential use as a wound healing adjuvant therapy. Common-plantain extracts were obtained by infusion and ultrasound extraction, and their total polyphenolic content and antioxidant capacity were determined by spectrophotometry. The best extract, which was obtained by infusion, was further encapsulated in sodium alginate in two different formulations. Fourier Transform Infrared Spectroscopy (FTIR) was used to demonstrate the existing interactions in the obtained common-plantain extract in the alginate formulations. The encapsulation efficiency was evaluated based on the total polyphenol content. These alginate gel formulations were further used in vitro to determine their biocompatibility and antioxidant and anti-inflammatory effects by spectrophotometry and ELISA, as well as their ability to stimulate fibroblast migration (scratch test assay) at different time points. In addition, the collagen 1 and 3 levels were determined by Western blot analysis. The data showed that the microencapsulated plantain extract formulations induced an antioxidant, anti-inflammatory effect, enhanced collagen production and increased wound closure in the first 8 h of their application. These results are encouraging for the use of this alginate plantain extract formulation as an adjuvant for skin wound healing.

Non-Contact and Self-Calibrated Photopyroelectric Method for Complete Thermal Characterization of Porous Materials.

A general theory of a photopyroelectric (PPE) configuration, based on an opaque sample and transparent pyroelectric sensor, backing and coupling fluids is developed. A combined back-front detection investigation, based on a frequency scan of the phase of the PPE signals, followed by a self-normalization of the phases' behavior, leads to the possibility of simultaneously measuring both thermal effusivity and diffusivity of a solid sample. A particular case of this configuration, with no coupling fluid at the sample/backing interface and air instead of coupling fluid at the sample/sensor interface (non-contact method) is suitable for simultaneous measurement ofboth thermal diffusivity and effusivity (in fact complete thermal characterization) of porous solids. Compared with the already proposed configurations for investigations of porous materials, this novel configuration makes use of a fitting procedure with only one fitting parameter, in order to guarantee the uniqueness of the solution. The porous solids belong to a class of materials which are by far not easy to be investigated using PPE. To the best of our knowledge, porous materials represent the only type of compounds, belonging to condensed matter, which were not taken into consideration (until recently) as potential samples for PPE calorimetric investigations. Consequently, the method proposed in this paper complete the area of applications of the PPE method. Applications on some porous building materials and cellulose-based samples validate the theory.

Effect of Microencapsulated Basil Extract on Cream Cheese Quality and Stability.

The antimicrobial and antioxidant effects of plant extracts are well known, but their use is limited because they affect the physicochemical and sensory characteristics of products. Encapsulation presents an option to limit or prevent these changes. The paper presents the composition of individual polyphenols (HPLC-DAD-ESI-MS) from basil (Ocimum basilicum L.) extracts (BE), and their antioxidant activity and inhibitory effects against strains of Staphylococcus aureus, Geobacillus stearothermophilus, Bacillus cereus, Candida albicans, Enterococcus faecalis, Escherichia coli, and Salmonella Abony. The BE was encapsulated in sodium alginate (Alg) using the drop technique. The encapsulation efficiency of microencapsulated basil extract (MBE) was 78.59 ± 0.01%. SEM and FTIR analyses demonstrated the morphological aspect of the microcapsules and the existence of weak physical interactions between the components. Sensory, physicochemical and textural properties of MBE-fortified cream cheese were evaluated over a 28-day storage time at 4 °C. In the optimal concentration range of 0.6-0.9% (w/w) MBE, we determined the inhibition of the post-fermentation process and the improvement in the degree of water retention. This led to the improvement of the textural parameters of the cream cheese, contributing to the extension of the shelf life of the product by 7 days.

The Effect of Aromatic Plant Extracts Encapsulated in Alginate on the Bioactivity, Textural Characteristics and Shelf Life of Yogurt.

The article investigated the antioxidant and antimicrobial activity of extracts from two aromatic plants-Satureja hortensis L. (SE) and Rosmarinus officinalis L. (RE), encapsulated in alginate, on-yogurt properties. The encapsulation efficiency was controlled by FTIR and SEM analysis. In both extracts, the individual polyphenol content was determined by HPLC-DAD-ESI-MS. The total polyphenol content and the antioxidant activity were spectrophotometrically quantified. The antimicrobial properties of SE and RE against gram-positive bacteria (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, Geobacillus stearothermophilus), gram-negative bacteria (Escherichia coli, Acinetobacter baumannii, Salmonella abony) and yeasts (Candida albicans) were analyzed in vitro. The encapsulated extracts were used to prepare the functional concentrated yogurt. It was established that the addition of 0.30-0.45% microencapsulated plant extracts caused the inhibition of the post-fermentation process, the improvement of the textural parameters of the yogurt during storage, thus the shelf life of the yogurt increased by seven days, compared to the yogurt simple. Mutual information analysis was applied to establish the correlation between the concentration of the encapsulated extracts on the sensory, physical-chemical, and textural characteristics of the yogurt.

The Antibacterial Properties of Nanocomposites Based on Carbon Nanotubes and Metal Oxides Functionalized with Azithromycin and Ciprofloxacin.

Different microorganisms are present in nature, some of which are assumed to be hazardous to the human body. It is crucial to control their continuing growth to improve human life. Nanomaterial surface functionalization represents a current topic in continuous evolution that supports the development of new materials with multiple applications in biology, medicine, and the environment. This study focused on the antibacterial activity of different nanocomposites based on functionalized multi-walled carbon nanotubes against four common bacterial strains. Two metal oxides (CuO and NiO) and two antibiotics (azithromycin and ciprofloxacin) were selected for the present study to obtain the following nanocomposites: MWCNT-COOH/Antibiotic, MWCNT-COOH/Fe3O4/Antibiotic, and MWCNT-COOH/Fe3O4/MO/Antibiotic. The present study included two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Ciprofloxacin (Cip) functionalized materials (MWCNT-COOH/Fe3O4/Cip) were most efficient against all tested bacterial strains; therefore, we conclude that Cu and Ni reduce the effects of Cip. The obtained results indicate that the nanocomposites functionalized with Cip are more effective against selected bacteria strains compared to azithromycin (Azi) functionalized nanocomposites. The current work determined the antibacterial activities of different nanocomposites and gave fresh insights into their manufacture for future research regarding environmental depollution.

Synthesis and Characterization of MWCNT-COOH/Fe3O4 and CNT-COOH/Fe3O4/NiO Nanocomposites: Assessment of Adsorption and Photocatalytic Performance.

In this study the adsorption and photodegradation capabilities of modified multi-walled carbon nanotubes (MWCNTs), using tartrazine as a model pollutant, is demonstrated. MWCNT-COOH/Fe3O4 and MWCNT-COOH/Fe3O4/NiO nanocomposites were prepared by precipitation of metal oxides in the presence of MWCNTs. Their properties were examined by X-ray diffraction in powder (XRD), Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Raman spectroscopy, synchrotron-based Scanning PhotoElectron Microscopy (SPEM), and Brunauer-Emmett-Teller (BET) analysis. It was found that the optimal adsorption conditions were pH 4 for MWCNT-COOH/Fe3O4 and pH 3 for MWCNT-COOH/Fe3O4/NiO, temperature 25 °C, adsorbent dose 1 g L-1, initial concentration of tartrazine 5 mg L-1 for MWCNT-COOH/Fe3O4 and 10 mg L-1 for MWCNT-COOH/Fe3O4/NiO and contact time 5 min for MWCNT-COOH/Fe3O4/NiO and 15 min for MWCNT-COOH/Fe3O4. Moreover, the predominant degradation process was elucidated simultaneously, with and without simulated sunlight irradiation, using thermal lens spectrometry (TLS) and UV-Vis absorption spectrophotometry. The results indicated the prevalence of the photodegradation mechanism over adsorption from the beginning of the degradation process.

Structural studies of various olmesartan solvates.

Seven solvates of the angiotensin II receptor blocker agent olmesartan (C24H26N6O3), namely, the methanol (C24H26N6O3·CH4O), ethanol (C24H26N6O3·C2H6O), isopropanol (C24H26N6O3·C3H8O), isobutanol (C24H26N6O3·C4H10O), 2-ethoxyethanol (C24H26N6O3·C4H10O2), chloroform (C24H26N6O3·CHCl3) and acetonitrile (C24H26N6O3·C2H3N) solvates, were successfully obtained. The crystal structures were determined using the single-crystal X-ray diffraction technique and the structural features are described, each solvate containing one molecule of olmesartan and one of solvent in the asymmetric unit. The samples were also analyzed by powder X-ray diffraction. Total lattice energies and binding energies between the olmesartan and solvent molecules were evaluated, which can be partitioned into electrostatic, polarization, dispersion and repulsion components. Hirshfeld and fingerprint plot analysis was performed to highlight the intermolecular contacts. Hydrogen bonding and supramolecular arrangements were comparatively studied for the seven solvates.

The Effect of TiO2 Nanoparticles on the Composition and Ultrastructure of Wheat.

The present work aims to follow the influence of TiO2 nanoparticles (TiO2 NPs) on bioactive compounds, the elemental content of wheat, and on wheat leaves' ultrastructure. Synthesized nanoparticles were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and transmission electron microscopy (TEM). The concentration of phenolic compounds, assimilation pigments, antioxidant capacity, elemental content, as well as the ultrastructural changes that may occur in the wheat plants grown in the presence or absence of TiO2 NPs were evaluated. In plants grown in the presence of TiO2 NPs, the amount of assimilating pigments and total polyphenols decreased compared to the control sample, while the antioxidant activity of plants grown in amended soil was higher than those grown in control soil. Following ultrastructural analysis, no significant changes were observed in the leaves of TiO2-treated plants. Application of TiO2 NPs to soil caused a significant reaction of the plant to stress conditions. This was revealed by the increase of antioxidant capacity and the decrease of chlorophyll, total polyphenols, and carotenoids. Besides, the application of TiO2 NPs led to significant positive (K, Zn, Br, and Mo) and negative (Na, Mn, Fe, As, Sr, Sb, and Ba) variation of content.

The Impact Assessment of CuO Nanoparticles on the Composition and Ultrastructure of Triticum aestivum L.

In the present study, the effects of copper oxide nanoparticles (CuO NPs) on bioactive compounds, the ultrastructural modifications which can occur, and elemental content of wheat were investigated. Changes in the wheat plants grown in presence or absence of CuO NPs were estimated. The application of CuO NPs decreased the amounts of chlorophylls and carotenoids and increased the amounts of polyphenols and antioxidant capacity. Ultrastructural analysis showed that the plants treated with CuO NPs were negatively affected. Soil amending completely inhibited the accumulation of seventeen elements, while K, Br, Al, and Zn were accumulated and Cl, Na, Ba, and Sr content decreased in wheat samples, regardless of the type of NPs applied. The application of chemically obtained NPs induced the most significant changes, completely blocking the assimilation of Fe, Mo, As, Sb, and Sm, and favoring much higher accumulation of Br than biogenic NPs. The decrease in chlorophylls and carotenoids is correlated with increase in antioxidant capacity, and occurs with increase of Mo, Al, Mg, K, Zn, and Ca content. The behavior of total polyphenols is correlated with Br content, and antagonist to Al behavior. From the point of view of bioactive compounds, the most affected plants were those that grew in the presence of CuO-NP-cel, while from the point of view of elementary analysis, the most affected plants were those grown in the presence of CuO-NP. By corroborating the obtained results, it was found that the CuO NPs have a negative effect on wheat plants.

Ketoconazole-p aminobenzoic cocrystal, an improved antimycotic drug formulation, does not induce skin sensitization on the skin of BALBc mice.

Fungal infections are a growing global health problem. Therefore, our group has synthetized and characterized an improved antimycotic by co-crystallization of ketoconazole and para-amino benzoic acid, named KET-PABA. The aim was to increase bioavailability, biocompatibility, and efficiency of the parent drug-ketoconazole. Based on our previous results showing the cocrystal improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency compared to ketoconazole, the current study investigated the local possible side effects induced on the skin of BALBc mice by the application of KET-PABA cocrystal, in view of a further use as a topically applied antimycotic drug. A specific test (mouse ear-swelling test) was used, combined with the histopathological examination and the measurement of pro and anti-inflammatory cytokines and inflammation mediators. KET-PABA application was safe, without signs of skin sensitization shown by the mouse ear sensitization test, or histopathology. KET-PABA strongly inhibited proinflammatory cytokines such as IL1 α, IL1 ß, IL6 and TNF α, and other proinflammatory inducers such as NRF2, compared to vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NF-κB pathway. Overall, KET-PABA application induced no sensitization, moreover, it decreased the skin levels of proinflammatory molecules. The lack of skin sensitization effects on BALBc mice skin along with the inhibition of the proinflammatory markers show a good safety profile for topical applications of KET-PABA and show promise for a further clinical use in the treatment of cutaneous mycosis.

Investigation of L-Tryptophan Electrochemical Oxidation with a Graphene-Modified Electrode.

A graphene sample (EGr) was prepared by electrochemical exfoliation of graphite rods in solution containing 0.05 M (NH4)2SO4 + 0.1 M H3BO3 + 0.05 M NaCl. The exfoliation was performed by applying a constant voltage (12 V) between the graphite rods, while the temperature was kept constant (18 °C) with a temperature-controlled cryostat. The structural investigation of the graphene sample, performed by X-ray powder diffraction (XRD), revealed that the sample consists of a mixture of few-layer (69%), multi-layer graphene (14%) and graphene oxide (17%). In addition, XPS analysis proved that the sample was triple-doped with heteroatoms such as nitrogen (1.7 at%), sulfur (2.5 at%), and boron (3 at%). The sample was deposited onto the surface of a clean, glassy carbon electrode (GC) and investigated for the non-enzymatic electrochemical detection of L-tryptophan (TRP). The electrocatalytic properties of the EGr/GC electrode led to a considerable decrease in the oxidation potential from +0.9 V (bare GC) to +0.72 V. In addition, the EGr/GC electrode has higher sensitivity (two times) and a lower detection limit (ten times) in comparison with the bare GC electrode.

Evaluation of CNT-COOH/MnO2/Fe3O4 nanocomposite for ibuprofen and paracetamol removal from aqueous solutions.

The nanocomposite CNT-COOH/MnO2/Fe3O4 was synthesized and characterized by different techniques, namely X-ray diffraction, Fourier-transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, energy dispersive spectroscopy, thermogravimetric analysis, Brunauer-Emmett-Teller analysis, magnetic measurement, point of zero charge and hydrophobicity index. Analyzes revealed the groups -COOH, MnO2 and Fe3O4 attached to the carbon nanotubes, the acidic character of the obtained nanocomposite and its stability. The surface area for the obtained nanocomposite was 114.2 m2 g-1. The prepared nanocomposite was used for adsorption of ibuprofen and paracetamol from aqueous solution. Isotherm, kinetic and thermodynamic parameters were determined for predicting the ibuprofen and paracetamol adsorption on synthetized nanocomposite. The equilibrium data obtained from adsorption were well represented by Langmuir model and kinetics data were well fitted by the pseudo-second order model. The maximum adsorption capacity obtained for ibuprofen and paracetamol was 103.093 mg g-1, 80.645 mg g-1 respectively. The thermodynamic analysis showed that the adsorption process for both pollutants was spontaneous and endothermic. The synthetized nanocomposite can be a suitable new absorbent for ibuprofen and paracetamol removal from aqueous solutions due to its high adsorbing capacity and it can be separated by an external magnetic field.

Green Synthesis of Ag-MnO2 Nanoparticles using Chelidonium majus and Vinca minor Extracts and Their In Vitro Cytotoxicity.

Medicinal plants are often used as reducing agents to prepare metal nanoparticles through green-synthesis due to natural compounds and their potential as chemotherapeutic drugs. Thus, three types of eco-friendly Ag-MnO2 nanoparticles (Ag-MnO2NPs) were synthesized using C. majus (CmNPs), V. minor (VmNPs), and a 1:1 mixture of the two extracts (MNPs). These NPs were characterized using S/TEM, EDX, XRD, and FTIR methods, and their biological activity was assessed in vitro on normal keratinocytes (HaCaT) and skin melanoma cells (A375). All synthesized NPs had manganese oxide in the middle, and silver oxide and plant extract on the exterior. The NPs had different forms (polygonal, oval, and spherical), uniformly distributed, with crystalline structures and different sizes (9.3 nm for MNPs; 10 nm for VmNPs, and 32.4 nm for CmNPs). The best results were obtained with VmNPs, which reduced the viability of A375 cells up 38.8% and had a moderate cytotoxic effect on HaCaT (46.4%) at concentrations above 500 µg/mL. At the same concentrations, CmNPs had a rather proliferative effect, whereas MNPs negatively affected both cell lines. For the first time, this paper proved the synergistic action of the combined C. majus and V. minor extracts to form small and uniformly distributed Ag-MnO2NPs with high potential for selective treatments.

Ketoconazole-p-aminobenzoic Acid Cocrystal: Revival of an Old Drug by Crystal Engineering.

The 1:1 cocrystal of the antifungal agent ketoconazole with p-aminobenzoic acid was successfully crystallized and systematically characterized by a physical and pharmacological point of view. Crystal structure determination confirmed the cocrystal identity, giving full insight in its crystal packing and degree of disorder. Powder dissolution measurements revealed a 10-fold aqueous solubility increase that induces a 6.7-fold oral bioavailability improvement compared to ketoconazole. In vitro cell assays showed a good toxicity profile of the cocrystal with lower oxidative stress and inflammation and enhanced antifungal activity against several Candida species. The in vivo study of the cocrystal indicated similar pharmacokinetic profiles and liver toxicity with increased transaminases, as reported for ketoconazole. Notably, besides minor signs of inflammation, no morphological changes in liver parenchyma or signs of fibrosis and necrosis were detected. The enhanced solubility and oral bioavailability of the cocrystal over ketoconazole, together with the improved antifungal activity and good in vitro/in vivo toxicity, indicate its potential use as an alternative antifungal agent to the parent drug. Our results bring evidence of cocrystallization as a successful approach for bioavailability improvement of poorly soluble drugs.

Data on the removal of Optilan Blue dye from aqueous media using starch-coated green synthesized magnetite nanoparticles.

In this data article, we present supplementary data related to the research article entitled "Starch-coated green synthesized magnetite nanoparticles for removal of textile dye Optilan Blue from aqueous media" Stan et al., 2019. Data interpretations are included in the related research article Stan et al., 2019. The synthesized starch-coated Fe3O4 nanoparticles (ST-coated Fe3O4 NPs) were analyzed by scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM) to illustrate the shape and surface coating of nanoparticles. Moreover, the Brunauer-Emmett-Teller (BET) technique was used to evidence starch deposition on magnetite nanoparticles. The obtained nanocomposites were used for adsorption of Optilan Blue (OB) in batch conditions and the optimum agitation speed and point of zero charge (pHpzc) were established. After OB adsorption on ST-coated Fe3O4 NPs, the nanocomposites were analyzed by transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). The stability of starch coated Fe3O4 NPs in the acidic as well as alkaline pH was also evidenced by FTIR spectroscopy. In addition, to test the stability of ST-coated Fe3O4 NPs, leaching experiments were carried out. The experimental data were compared with isotherm and kinetic models in order to determine the most suitable for fitting.

The efficiency of the multi-walled carbon nanotubes used for antibiotics removal from wastewaters generated by animal farms.

In the recent years, residual antibiotics are considered to be emerging environmental pollutants due to their continuous input and persistence into the aquatic ecosystem even at low concentrations. Therefore, these are necessary to develop efficient methods for the wastewater treatment. The present paper describes the efficiency of several types of multi-walled carbon nanotubes (MWCNTs) for the retention of the selected antibiotics (ampicillin, ceftazidime, cefepime, imipenem, piperacillin, tazobactam, tetracycline, erythromycin, ciprofloxacin, norfloxacin, vancomycin, gentamicin, sulfamethoxazole, and thrimetoprim) from aqueous (synthetic) solutions and wastewater samples. The functionalized MWCNTs were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The obtained antibiotic percentage of retention was evaluated by quantitative assessment using high-performance liquid chromatography coupled with the diode array, fluorescence, and mass spectrometer detector (HPLC-DAD/FD/MS), after the solid-phase extraction (SPE) with Oasis HLB cartridges. The retention percentages of the selected antibiotics from waters ranged between ∼40 and 97%, with the exception of sulfamethoxazole and trimethoprim. The best percentages of retention were obtained for norfloxacin 97.03% and ciprofloxacin 97.10%. The suspensions of the MWCNTs improved the antibiotics removal from wastewaters. Removal of antibiotics from wastewaters using nanotechnology, in order to reduce their negative effects and antibiotic resistance, is a promising tool in the future wastewaters treatment.

Crystal Structure and Desolvation Behaviour of the Tadalafil Monosolvates with Acetone and Methyl Ethyl Ketone.

Crystal structures of Tadalafil (TDF) monosolvated forms with acetone (ACE) and methyl ethyl ketone (MEK) were determined by single-crystal X-ray diffraction in which same persistent chains of TDF molecules are present as in the reported structures. The solvates crystallize in a higher orthorhombic symmetry than the known forms with monoclinic structures. Weak interactions between TDF and solvent molecules are present in both solvates, leading to slight conformational distortions of TDF molecules. The MEK solvate showed slightly higher stability than the ACE solvate, regardless of their highly similar molecular conformations and crystal packing. Desolvation into anhydrous TDF was achieved by heating, exposure to temperature and relative humidity and by mechanical stress. The high solubility of TDF in ACE and MEK solvents combined with the ease of desolvation of the resulting solvated forms indicates the viability of the solvates use as intermediates in the TDF crystallization process.

Crystal structure and physicochemical characterization of ambazone monohydrate, anhydrous, and acetate salt solvate.

The crystal structures of the monohydrate and anhydrous forms of ambazone were determined by single-crystal X-ray diffraction (SC-XRD). Ambazone monohydrate is characterized by an infinite three-dimensional network involving the water molecules, whereas anhydrous ambazone forms a two-dimensional network via hydrogen bonds. The reversible transformation between the monohydrate and anhydrous forms of ambazone was evidenced by thermal analysis, temperature-dependent X-ray powder diffraction and accelerated stability at elevated temperature, and relative humidity (RH). Additionally, a novel ambazone acetate salt solvate form was obtained and its nature was elucidated by SC-XRD. Powder dissolution measurements revealed a substantial solubility and dissolution rate improvement of acetate salt solvated form in water and physiological media compared with ambazone forms. Also, the acetate salt solvate displayed good thermal and solution stability but it transformed to the monohydrate on storage at elevated temperature and RH. Our study shows that despite the requirement for controlled storage conditions, the acetate salt solvated form could be an alternative to ambazone when solubility and bioavailability improvement is critical for the clinical efficacy of the drug product.