Search Results (566)

Salbutamol sulfate is a selective β2-receptor agonist used to treat asthma and chronic obstructive pulmonary disease. The crystals of salbutamol sulfate usually appear as needles with a relatively large aspect ratio, showing poor powder properties. In this study, spherical particles of salbutamol sulfate were obtained via antisolvent crystallization. Four different antisolvents, including ethanol, n-propanol, n-butanol, and sec-butanol, were selected, and their effects on crystal form and morphology were compared. Notably, a new solvate of salbutamol sulfate with sec-butanol has been obtained. The novel crystal form was characterized by single-crystal X-ray diffraction, revealing a 1:1 stoichiometric ratio between solvent and salbutamol sulfate in the crystal lattice. In addition, the effects of crystallization temperature, solute concentration, ratio of antisolvent to solvent, feeding rate, and stirring rate on the morphology of spherical particles were investigated in different antisolvents. We have found that crystals grown from the n-butanol–water system at optimal conditions (25 °C, antisolvent/solvent ratio of 9:1, and drug concentration of 0.2 g·mL⁻¹) could be developed into compact and uniform spherulites. The morphological evolution process was also monitored, and the results indicated a spherulitic growth pattern, in which sheaves of plate-like crystals gradually branched into a fully developed spherulite. This work paves a feasible way to develop new crystal forms and prepare spherical particles of pharmaceuticals. Full article

Boronic acids are an important class of molecules diversely used in organic synthesis, catalysis, medicinal chemistry, and for the design of functional materials. Particularly, aryl boronic acids in the solid state are known to exhibit pharmaceutical and photoluminescent properties for antimicrobial, sensing, and drug delivery applications. Furthermore, the phenazine molecule is known for its diverse pharmacological properties, including antibiotic activity. In the case of molecular crystalline solids, it is well established that understanding noncovalent interactions remains key to designing or engineering their functional properties. While both aryl boronic acids and phenazine molecules individually represent an important class of compounds, their co-assembly in the crystalline state is of interest within the context of supramolecular chemistry and crystal engineering. Herein, we report the supramolecular features of two newly synthesized cocrystals, which are composed of para-F/CF₃-substituted phenylboronic acids, respectively, and phenazine, as demonstrated by structure analysis by single-crystal X-ray diffraction. Full article

The emergence of antimicrobial resistance and the increasing demand for a healthier lifestyle have set new goals for science and industry. In the search for new, more effective, and environmentally friendly antimicrobial agents, special attention is being paid to natural resources. In this regard, essential oils derived from plants, which are widely used in the cosmetic, food, and pharmaceutical industries, are one of the solutions. In view of the above, this study aims to investigate the biological effects of Abies alba essential oil (AAEO). The chemical profile of AAEO was evaluated by GC/MS analysis, which revealed a high abundance of limonene (52.2%) and α-pinene (36.2%). Antioxidant activity evaluation showed a higher potential of AAEO in scavenging ABTS radical species with an IC₅₀ value of 1.18 ± 0.05 mg/mL. In vitro antimicrobial activity was determined by disc diffusion and minimum inhibitory concentration assays and showed that AAEO was more efficient in inhibiting the growth of G⁺ bacterial species. On contrary, in situ evaluations of antimicrobial effects of AAEO on different food models (strawberry, kiwi, white radish, and beetroot) resulted in more efficient suppression of G⁻ bacterial species. Although AAEO showed low effects on yeasts determined by in vitro methods, in situ investigations showed its higher potential in eradication of Candida yeast. The antibiofilm properties of the AAEO matrix were determined by means of crystal violet assay and MALDI-TOF MS Biotyper analysis against biofilm-forming Salmonella enterica. The analysis performed led to the conclusion that AAEO, when applied prior to biofilm formation, may contribute to the removal of planktonic cells and alter the abiotic surface, thereby reducing the suitability of Salmonella enterica for microbial attachment. Full article

FmocFF is a highly versatile gelator whose π–π-stacking fluorenyl group and hydrogen-bonded peptide backbone permit gelation in a wide spectrum of solvents, providing a rich scaffold for crystal engineering. This study explores the synergistic effects of FmocFF organogels and solvent selection on controlling the polymorphic outcomes of nilutamide, a nonsteroidal antiandrogen drug with complex polymorphism. By systematically varying process parameters such as solvent type and concentration, we demonstrate remarkable control over crystal nucleation and growth pathways. Most significantly, we report the first ambient-temperature isolation of pure nilutamide Form II through acetonitrile-based FmocFF organogel, highlighting the unique interplay between solvent properties and gel fiber networks. Thermal analysis reveals that the organogel not only selectively templates Form II but also affects its thermal pathway. We also present compelling evidence for a new polymorph exhibiting second-harmonic generation (SHG) activity. This would represent the first non-centrosymmetric nilutamide form discovered, suggesting the gel matrix induces symmetry breaking during crystallization. We also characterize a previously unreported nilutamide–chloroform solvate through multiple analytical techniques including PXRD, DSC, FTIR, SXRD, and SHG microscopy. Our findings demonstrate that solvent-specific molecular recognition within gel matrices enables access to entirely new regions of polymorphic space, establishing gel-mediated crystallization as a broadly applicable platform technology for pharmaceutical solid form discovery under mild conditions. Full article

Background/Objectives: Increasing the solid-state landscape of an active pharmaceutical ingredient (API) by generating new crystalline forms (e.g., polymorphs, cyclodextrin (CD) inclusion complexes, co-crystals, and salts) can yield products with significantly enhanced biopharmaceutical properties (especially increased water solubility), thereby improving API delivery and extending its lifetime. The aim of this study was the isolation of new solid forms of the poorly water-soluble non-steroidal anti-inflammatory drug fenbufen (FBF), for which relatively few solid phases have been reported to date. Further motivation for the study is the recent finding that it has potential for repurposing to treat acute pancreatitis. Methods: Interventions for generating new solid forms of FBF included (a) polymorph screening with a variety of solvent media, (b) attempts to form solid inclusion complexes with the native cyclodextrins α-, β-, and γ-CD using various preparative methods, and (c) co-crystallization with a series of coformers to produce co-crystals and/or molecular salts. Results: No new polymorphic forms of FBF were identified, but screening with CDs resulted in isolation and characterization of a new solid inclusion complex with γ-CD. However, co-crystallization of FBF with the water-soluble coformer isonicotinamide yielded two new products, namely a 1:1 co-crystal and an unusual multi-component ionic co-crystal, whose aqueous solubility indicated significant enhancement of FBF solubility. Conclusions: Due to its extremely low water solubility, FBF presented challenges during the study aimed at modifying its crystalline form. However, two new supramolecular forms, a co-crystal and an ionic co-crystal, were isolated, the latter phase having potential for further formulation owing to its significantly enhanced solubility. Full article

A series of new isatin hydrazones bearing phosphorus-containing moiety was synthesized through a simple, high-yield and easy work-up reaction of phosphine oxide (Phosenazide) or phosphinate (2-chloroethyl (4-(dimethylamino)phenyl)(2-hydrazinyl-2-oxoethyl)phosphinate, CAPAH) hydrazides with aryl-substituted isatins. The ³¹P NMR technique showed that, in most cases, out of 12 examples in solution, the ratio of the two spatial isomers varied from 1:1 to 1:3. Quantum chemical calculations confirmed the predominance of Z,syn form both in the gas phase and in solution. According to X-ray analysis data in crystals, they exist only in Z,syn form too. Most of the phosphine oxide derivatives and 5-methoxy- and 5-bromoaryl phosphinate analogs exhibit anti-aggregant activity at the level of acetylsalicylic acid but inhibit platelet activation processes more effectively. The 5-chloro type phosphinate derivative exhibits anti-aggregant properties more effectively than acetylsalicylic acid under the conditions of the tissue factor (TF)-activated thromboelastography (TEG) model, the ex vivo thrombosis model. Thus, all the obtained results can become the basis for future pharmaceutical developments to create effective anti-aggregation drugs with broad antithrombotic potential. Full article

Thermokinetic characterization of amorphous carbamazepine was performed utilizing non-isothermal differential scanning calorimetry (DSC) and thermogravimetry (TGA). Structural relaxation of the amorphous matrix was described in terms of the Tool–Narayanaswamy–Moynihan model with the following parameters: Δh* ≈ 200–300 kJ·mol⁻¹, β = 0.57, x = 0.44. The crystallization of the amorphous phase was modeled using complex Šesták–Berggren kinetics, which incorporates temperature-dependent activation energy and degree of autocatalysis. The activation energy of the crystal growth was determined to be >320 kJ·mol⁻¹ at the glass transition temperature (T_g). Owing to such a high value, the amorphous carbamazepine is stable at T_g, allowing for extensive processing of the amorphous phase (e.g., self-healing of the quench-induced mechanical defects or internal stress). A discussion was conducted regarding the converse relation between the activation energies of relaxation and crystal growth, which is possibly responsible for the absence of sub-T_g crystal growth modes. The high-temperature thermal decomposition of carbamazepine proceeds via multistep kinetics, identically in both an inert and an oxidizing atmosphere. A complex reaction mechanism, consisting of a series of consecutive and competing reactions, was proposed to explain the second decomposition step, which exhibited a temporary mass increase. Whereas a negligible degree of carbamazepine degradation was predicted for the temperature characteristic of the pharmaceutical hot-melt extrusion (~150 °C), the degradation risk during the pharmaceutical 3D printing was calculated to be considerably higher (1–2% mass loss at temperatures 190–200 °C). Full article

Background: α-Hydroxyphosphonates, one of the most prominent classes of phosphonates, remain of utmost importance because of their potential and real biological activity as pharmaceutical or pesticide agents. The effect is the consequence of their enzyme inhibitory properties. Objectives: It was planned to make available new heterocyclic hydroxyphosphonate derivatives with cytotoxic activity. Methods: After optimizing the synthesis, 23 members of a new family, α-hydroxy-α-(benzothiophen-2-yl)-methylphosphonates, were prepared by the Pudovik reaction of benzo[b]thiophene-2-carboxaldehydes and diethyl phosphite. The addition was performed at 26 °C in the presence of triethylamine as the catalyst. One of the products was also characterized by single-crystal X-ray analysis. Results: The cytotoxic effect of the α-hydroxy-α-benzothiophenyl-methylphosphonates was tested on U266 myeloma, A2058 melanoma, HT-29 colon, and EBC-1 lung cancer cell lines. Most of the molecules showed significant activity; the greatest effects were seen after treatment with hydroxyphosphonates with a trifluoromethyl group in the benzene ring. Conclusions: The cytotoxic activity of the newly synthesized α-hydroxyphosphonates is encouraging to find even better derivatives. Full article

Stimuli-sensitive (in situ) drug delivery systems are a dynamically developing area of pharmaceutical research. Over the past decade, the number of studies on such systems has doubled. Among these, phase-inversion (or phase-sensitive) formulations, which were among the earliest proposed, offer significant advantages, including enhanced stability and stimuli-responsiveness. However, phase-inversion systems have remained relatively understudied. Despite the existence of three patented technologies (Atrigel^®, BEPO^®, FluidCrystal^®) for delivery systems utilizing phase inversion for various routes of administration, the absence of unified approaches to development and standardization has significantly impeded the introduction of novel, effective drugs into clinical practice. This review examined the main polymers and solvents used to create phase-inversion compositions and discussed the feasibility of introducing other excipients to modify the systems’ physicochemical properties. The most commonly used polymers included polylactide-co-glycolide, shellac, and polylactic acid. The most frequently used solvents were N-methylpyrrolidone and dimethyl sulfoxide. Following an analysis of clinical studies of phase-sensitive drugs conducted over the past 25 years, as well as original research indexed in PubMed, ScienceDirect, and Google Scholar, the main problems hindering the broader adoption of phase-inversion systems in clinical practice were identified, and recommendations for further development in this promising area were provided. Full article

Crystallization in microgravity has measurable benefits, from molecules as simple as sodium chloride to elaborate protein complexes. However, small organic molecules have not been reported. The small organic molecules glycine, famoxadone, carbamazepine, and 5-methyl-2-((2-nitrophenyl)amino)thiophene-3-carbonitrile (ROY) were crystallized on Earth under microgravity conditions. When comparing these different gravity crystallization conditions, we found the formation of different polymorphs and/or habits for glycine, carbamazepine, and ROY. The crystallization of famoxadone occurred more slowly in microgravity. The differences in size, appearance, and, in the case of ROY, color, are detailed in this report. Full article

Addressing the limitations of poor piezoelectric photocatalytic activity and insufficient magnetic recovery in pure BiFeO₃ nanoparticles, Gd and Zr co-doped BiFeO₃ nanoparticles were synthesized via the sol-gel method. The structural characterization revealed a rhombohedral-to-orthorhombic phase transition with reduced grain size (~35 nm) and lattice distortion due to dopant incorporation. An XPS analysis confirmed Fe³⁺ dominance and oxygen vacancy enrichment, while optimized BGFZ9 exhibited enhanced remanent magnetization (0.1753 emu/g, 14.14 increase) compared to undoped BFO. The synergistic piezo-photocatalytic system achieved 81.08% Ofloxacin degradation within 120 min (rate constant: 0.0136 min⁻¹, 1.26 higher than BFO) through stress-induced piezoelectric fields that promoted electron transfer for ·O₂⁻/·OH radical generation via O₂ reduction. The Ofloxacin degradation efficiency decreased to 24.36% after four cycles, with structural integrity confirmed by XRD phase stability. This work demonstrates a triple-optimization mechanism (crystal phase engineering, defect modulation, and magnetic enhancement) for designing magnetically recoverable multiferroic catalysts in pharmaceutical wastewater treatment. Full article

Background: Tetrabenazine (brand name Nitoman and Xenazine) is a compound used to treat neurological and psychiatric disorders. Due to its low solubility, this drug is administered to patients in high doses, which produces side effects. Methods: To overcome these deficiencies, we prepared, using the mechanochemical method, three salts of tetrabenazine with three coformers: oxalic, fumaric, and succinic acid. The new solid forms were identified by X-ray powder diffraction (XRPD). Results: Full structural characterization was performed by single-crystal X-ray diffraction (SC-XRD), which revealed that the supramolecular interactions in the new solid forms were achieved by proton transfer between the coformer and the nitrogen of the tetrabenazine molecule. The salts formation was also evidenced by thermal analyses (DSC) and infrared spectroscopy (FTIR). Furthermore, the physical stability of the salts was evaluated under extreme temperature and humidity conditions. Conclusions: From a pharmaceutical perspective, UV-VIS tests of the new salts dissolved in water revealed a significant improvement in their solubility, which could improve their bioavailability in therapeutic applications. Full article

Background: Neem seed oil (Azadirachta indica A. Juss) is widely used in the pharmaceutical, agricultural, and food industries due to its antiseptic, fungicidal, pesticidal, and antioxidant properties, attributed to over 300 bioactive compounds and a high content of unsaturated fatty acids. Methods: This study aimed to characterize a commercial sample of neem oil regarding its physicochemical properties and identity profile, using official methodologies from the American Oil Chemists’ Society (AOCS), and to compare the results with literature data. Results: The sample exhibited the following parameters: free fatty acids (2.0 ± 0.02%), acidity index (3.9 ± 0.04 mg KOH/g), peroxide value (3.2 ± 0.1 mEq/kg), iodine value (116 ± 12 g I₂/100 g), and saponification index (198 ± 8 mg KOH/g). The predominant coloration was yellowish, with total chlorophyll and carotenoid levels below the equipment’s quantification limits. Fatty acid composition was mainly long-chain (C16–C18), with notable levels of linoleic acid (46%), oleic acid (28%), palmitic acid (12%), linolenic acid (5.5%), and stearic acid (4.1%). The triacylglycerol profile showed a predominance of triunsaturated (51%) and diunsaturated species (41%). Differential scanning calorimetry (DSC) analysis revealed crystallization events between −6 °C and −57 °C and fusion events between −44 °C and −1 °C, consistent with the high unsaturation level of the lipids. Conclusions: The analyzed neem oil sample meets quality and identity criteria, making it suitable for various industrial applications. The characterization confirms its potential and aligns with literature data, emphasizing its relevance for industrial use. Full article

Small-scale modular apparatuses in continuously operated plants are promising for current and future production processes in fine and specialty chemistry. Different lab-scale crystallizers have been developed and characterized as part of the ENPRO-TeiA project—separation processes with efficient and intelligent apparatuses. Two research groups at TU Dortmund University have investigated four miniaturized crystallization apparatuses for cooling crystallization and characterized them for scaling up to pilot scale with industrial partners. The use in an industrial environment was successfully demonstrated for two types of crystallizers: the stirred tank cascade as well as a draft tube baffle crystallizer. The ENPRO-TeiA project was thus able to prototypically demonstrate the manufacturer-independent investigation and scaling of modular systems for the crystallization step, which is an essential cornerstone for the process development acceleration for sustainable production in the pharmaceutical and chemical industries. Full article

Objectives: Hot-melt extrusion (HME) offers a solvent-free, scalable approach for manufacturing pharmaceutical co-crystals (CCs), aligning with the industry’s shift to continuous manufacturing (CM). However, challenges like undefined yield optimization, insufficient risk management, and limited process analytical technology (PAT) integration hinder its industrial application. This study aimed to develop a proof-of-concept HME platform for CCs, assess process risks, and evaluate PAT-enabled monitoring to facilitate robust production. Methods: Using carbamazepine (CBZ) and nicotinamide (NIC) as model compounds, an HME platform compatible with PAT tools was established. A systematic risk assessment identified five key risk domains: materials, machinery, measurement, methods, and other factors. A Box–Behnken design of experiments (DoE) evaluated the impact of screw speed, temperature, and mixing sections on CC quality. Near-infrared (NIR) spectroscopy monitored CBZ-NIC co-crystal formation in real time during HME process. Results: DoE revealed temperature and number of mixing sections significantly influenced particle size (D₅₀: 2.0–4.0 μm), while screw speed affected efficiency. NIR spectroscopy detected a unique CC absorption peak at 5008.3 cm⁻¹, enabling real-time structural monitoring with high accuracy (R² = 0.9999). Risk assessment highlighted material attributes, process parameters, and equipment design as critical factors affecting CC formation. All experimental batches yielded ≥ 94% pure CCs with no residual starting materials, demonstrating process reproducibility and robustness. Conclusions: Overall, this work successfully established a continuous hot-melt extrusion (HME) process for manufacturing CBZ-NIC co-crystals, offering critical insights into material, equipment, and process parameters while implementing robust in-line NIR monitoring for real-time quality control. Additionally, this work provides interpretable insights and serves as a basis for future machine learning (ML)-driven studies. Full article