Microwave-assisted synthesis of numerous bioactive scaffolds has gained much attention of late in organic chemistry. Most of the heterocyclic rings can be synthesized using the microwave irradiation ...method. This application is further used in the synthesis of active pharmaceutical ingredients containing heterocycle moiety. These bioactive heterocyclic derivatives synthesized by microwave-assisted one-pot multicomponent reaction, have significant anticancer, antibacterial, and antimicrobial properties. Herein, we summarize significant advances in the microwave-assisted synthesis of heterocycles and their useful bioactive properties.
Microwave-assisted bioactive heterocycles synthesis provides multi-component synthetic access to a large number of organic molecules having anti-cancer, anti-fungal, anti-bacterial, and other bio-activities. The microwave irradiation, ligand, catalyst, substrate, and reaction conditions were used to regulate the formation of numerous aza, oxa, and mixed heterocycles with different ring sizes and acyclic system with good yields, demonstrating the elegance, impact, and practicality of this microwave protocol. Display omitted
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The physical characteristics of raw materials determine powder compression and compaction performance as relevant in pharmaceutical processes. For instance, the influence of initial ...particle size on powder compression and the resulting strength of specimen are highly complex and are still not sufficiently understood. Existing studies are often limited to materials with well-defined deformation behaviour, such as purely brittle or ductile. However, the deformation behaviour of active pharmaceutical ingredients (APIs) is often more complex. In this study, the influence of initial particle size on powder compressibility and compactibility is systematically characterized by consideration of in-die compressibility, specific energies, quick elastic recovery, tablet porosity and, tensile strength for the binder microcrystalline cellulose and three APIs. The decrease of particle size leads to an increase of the resistance against compression by trend and probably to a different contribution of the acting deformation mechanisms. The compactibility is increased with decreasing particle size because of the increasing number of bonds in a cross-sectional area of the tablet, as found by the application of the model of Rumpf. Furthermore, it is found that the model of Rumpf combined with the JKR model provides a meaningful property function to estimate tablet tensile strength.
Organic solvent nanofiltration (OSN) has become increasingly important in petrochemical and pharmaceutical industries, demanding superior and robust membranes. Herein, we report advanced OSN ...processes by designing three‐dimensional covalent organic framework (3D COF) membranes through moderated interfacial crystallization. Nanoporous supports work as the moderator allowing the crystallization of 3D COF membranes. The 3D COF features sub‐nanometer and anti‐swelling channels, affording a sharp selectivity to fine targets with an exceptionally high and stable methanol permeance. Thus‐synthesized membrane exhibits a record stability against high‐concentration feeds and long‐term operation for ≈1000 h. Moreover, we unambiguously demonstrate that our membrane holds excellent practicality in purifying active pharmaceutical ingredients from organic liquids. This work reveals the great potential of distinctive 3D COFs in producing prominent OSN membranes for industrial applications.
A three‐dimensional covalent organic framework (3D COF) is prepared as a membrane for highly permselective and robust organic solvent nanofiltration. The membrane has an unprecedented methanol permeance. High‐performance purification of active pharmaceutical ingredients is also realized by the 3D COF membrane.
Dear Colleagues, In recent years, functional coating technology has attracted increased attention due to its effective potential for improved engineered materials. Growing demand for new materials ...with synergistic properties pushed research toward a new field to obtain innovative and smart coatings with functional capabilities that greatly differ from the conventional ones. In such a context, the expression of “functional coatings” has acquired specific relevance. This Special Issue will assess cutting-edge developments in this research area for the improvement and growth of actual performance, industrial scale-up, and marketability of functional coatings. This Special Issue is useful for researchers who are approaching this application context to improve their knowledge, with the aim of providing valuable scientific support for new research paths concerning functional surface engineering design and tailoring. Prof. Luigi Calabrese, Prof. Edoardo Proverbio Guest Editors
Continuous‐flow multi‐step synthesis takes the advantages of microchannel flow chemistry and may transform the conventional multi‐step organic synthesis by using integrated synthetic systems. To ...realize the goal, however, innovative chemical methods and techniques are urgently required to meet the significant remaining challenges. In the past few years, by using green reactions, telescoped chemical design, and/or novel in‐line separation techniques, major and rapid advancement has been made in this direction. This minireview summarizes the most recent reports (2017–2020) on continuous‐flow synthesis of functional molecules. Notably, several complex active pharmaceutical ingredients (APIs) have been prepared by the continuous‐flow approach. Key technologies to the successes and remaining challenges are discussed. These results exemplified the feasibility of using modern continuous‐flow chemistry for complex synthetic targets, and bode well for the future development of integrated, automated artificial synthetic systems.
Going with the flow: This Minireview summarizes the most recent reports (2017–2020) on continuous‐flow synthesis of functional molecules. Notably, several complex active pharmaceutical ingredients (APIs) have been prepared by the continuous‐flow approach. Key technologies to the successes and remaining challenges are discussed. These results exemplify the feasibility of using modern continuous‐flow chemistry for complex synthetic targets, and bode well for the future development of integrated, automated artificial synthetic systems.
Active pharmaceutical ingredients (APIs) can be prepared in many different solid forms and phases that affect their physicochemical properties and suitability for oral dosage forms. The development ...and commercialization of dosage forms require analytical techniques that can determine and quantify the API phase in the final drug product. 13C solid-state NMR (SSNMR) spectroscopy is widely employed to characterize pure and formulated solid APIs; however, 13C SSNMR experiments on dosage forms with low API loading are often challenging due to low sensitivity and interference from excipients. Here, fast magic angle spinning 1H SSNMR experiments are shown to be applicable for the rapid characterization of low drug load formulations. Diagnostic 1H SSNMR spectra of APIs within tablets are obtained by using combinations of frequency-selective saturation and excitation pulses, two-dimensional experiments, and 1H spin diffusion periods. Selective saturation pulses efficiently suppress the broad 1H SSNMR signals from the most commonly encountered excipients such as lactose and cellulose, allowing observation of high-frequency API 1H NMR signals. 1H SSNMR provides a 1–3 orders of magnitude reduction in experiment time compared to standard 13C SSNMR experiments, enabling diagnostic SSNMR spectra of dilute APIs within tablets to be obtained within minutes. The 1H SSNMR spectra can be used for quantification, provided calibrations are performed on a standard sample with known API loading.
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Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug molecules. ...Though nanosizing of drug particles has been proven to greatly enhance drugs dissolution rate and apparent solubility, nanosized materials have presented significant challenges for their formulation as solid dosage forms (e.g. tablets, capsules). This is due to the strong Van der Waals attraction forces between dry nanoparticles leading to aggregation, cohesion, and consequently poor flowability. In this review, the broad area of nanomedicines is overviewed with the primary focus on drug nanocrystals and the top-down and bottom-up methods used in their fabrication. The review also looks at how nanosuspensions of pharmaceutical drugs are generated and stabilised, followed by subsequent strategies for isolation of the nanoparticles. A perspective on the future outlook for drug nanocrystals is also presented.
Pharmaceutical compounds in wastewater have emerged as a significant concern for the aquatic environment. The use of in vitro bioassays represents a sustainable and cost-effective approach for ...assessing the potential toxicological risks of these biologically active compounds in wastewater and aligns with ethical considerations in research. It facilitates high-throughput analysis, captures mixture effects, integrates impacts of both known and unknown chemicals, and reduces reliance on animal testing. The core aim of the current review was to explore the practical application of in vitro bioassays in evaluating the environmental impacts of pharmaceuticals in wastewater. This comprehensive review strives to achieve several key objectives. First, it provides a summary categorisation of pharmaceuticals based on their mode of action, providing a structured framework for understanding their ecological significance. Second, a chronological analysis of pharmaceutical research aims to document their prevalence and trends over time, shedding light on evolving environmental challenges. Third, the review critically analyses existing bioassay applications in wastewater, while also examining bioassay coverage of representative compounds within major pharmaceutical classes. Finally, it explores the potential for developing innovative bioassays tailored for water quality monitoring of pharmaceuticals, paving the way for more robust environmental monitoring and risk assessment. Overall, adopting effect-based methods for pharmaceutical monitoring in water holds significant promise. It encompasses a broad spectrum of biological impacts, promotes standardized protocols, and supports a bioassay test battery approach indicative of different endpoints, thereby enhancing the effectiveness of environmental risk assessment.
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•In vitro bioassays can assess the toxicity of pharmaceuticals in water.•Pharmaceuticals classified based on their mode of action.•Current in vitro bioassay coverage of pharmaceutical classes explored.•About 8 out of 34 pharmaceutical classes possess validated in vitro bioassays.•Opportunities to develop novel bioassays for water quality monitoring highlighted.
•The crystallization of APIs in the microwells was monitored by microscopic imaging.•The crystalline images were analyzed by deep learning with high rate and accuracy.•The effects of microwell sizes ...on the growth kinetics of indomethacin were revealed.•The results were validated by the other representative drug and the scale-up experiment.
In the pharmaceutical industry, high-throughput crystallization (HTC) is an emerging strategy to accelerate the discovery of active pharmaceutical ingredients (APIs) with appropriate crystallization properties. It is typically processed in 96- and 384-well plates, which offer parallel crystallization vessels with microliter-scaled volume. However, the microwell size effect on crystallization kinetics at the scale of microtiters has not been fully investigated and remains unsolved. To address the issue, we proposed a novel deep-learning-based approach to investigate the effects of microwell sizes on the crystal growth kinetics of APIs. With a combination of microscopic imaging and deep learning, the massive information of indomethacin crystals was successfully obtained and analyzed in a high-throughput manner. And the relationships between crystallization properties (the average size, crystal size distribution, and the growth rate of crystals) and the size of the crystallization vessels were successfully revealed, which were further validated by the crystallization of ibuprofen and the scale-up experiment. Our research demonstrated the powerful capability of deep learning in processing complicated crystalline images. Moreover, our findings in the relationships between the size of the crystallization vessels and crystal growth kinetics are of great value in guiding the manufacture of APIs in the pharmaceutical industry.
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