Pharmaceutical Sciences Research Articles

Recent Advances in Photoinduced Borylation via N-Heterocyclic Carbene Boryl Radicals

Organoboron compounds, recognized as essential synthetic intermediates in organic chemistry, have found broad applications in pharmaceutical and materials science. In recent years, the development of novel boronating reagents has opened new avenues for the synthesis of organoboron. Among these, NHC–boranes, with their unique advantages, have garnered sustained interest and have evolved into significant precursors for boron-centered radicals, participating in a diverse array of visible light-induced borylation reactions. This article primarily focuses on the visible light-induced radical borylation reactions involving NHC–boranes, summarizing the latest advancements in the field, and offering inspiration for subsequent research.

A Pioneer Review on Intermolecular Hydrogen Bonding in Drug-Polymer Mixtures: Implication of a Stable Delivery System

Intermolecular hydrogen bonding plays a pivotal role in the stability and efficacy of drug-polymer mixtures, which are essential components in modern drug delivery systems. The knowledge of prominent interactions might provide a means to optimize the physiochemical stability of the developed targeted system. Hence, this review explores the fundamental principles of hydrogen bonding in drug-polymer interactions which can significantly influence the solubility, stability and release profiles of pharmaceutical formulations. The review provides an in-depth examination of the types of functional groups that participate in hydrogen bonding, the characterization techniques employed to study these interactions and the implications of hydrogen bonding on drug delivery. Case studies of successful drug-polymer systems stabilized by hydrogen bonding are presented, highlighting the practical applications and challenges associated with these formulations. Furthermore, the review discusses the future perspectives in this field, including the design of novel polymers and the integration of computational modeling to predict hydrogen bonding behavior. By understanding and leveraging hydrogen bonding, researchers can optimize drug delivery systems, ensuring enhanced bioavailability, controlled release and improved patient outcomes. This review aims to serve as a comprehensive resource for pharmaceutical scientists and formulators, offering insights into the strategic use of hydrogen bonding to develop more effective and stable drug delivery systems.

Structural basis for the binding of famotidine, cimetidine, guanidine, and pimagedine with serine protease

Serine proteases are among the important groups of enzymes having significant roles in cell biology. Trypsin is a representative member of the serine superfamily of enzymes, produced by acinar cells of pancreas. It is a validated drug target for various ailments including pancreatitis and colorectal cancer. Premature activation of trypsin is involved in the lysis of pancreatic tissues, which causes pancreatitis. It is also reported to be involved in colorectal carcinoma by activating other proteases, such as matrix metalloproteinase (MMPs). The development of novel trypsin inhibitors with good pharmacokinetic properties could play important roles in pharmaceutical sciences. This study reports the crystal structures of bovine pancreatic trypsin with four molecules; cimetidine, famotidine, pimagedine, and guanidine. These compounds possess binding affinity towards the active site (S1) of trypsin. The structures of all four complexes provided insight of the binding of four different ligands, as well as the dynamics of the active site towards the bind with different size ligands. This study might be helpful in designing of new potent inhibitors of trypsin and trypsin like serine proteases.

Mass Balance in Pharmaceutical Stress Testing: A Review of Principles and Practical Applications.

Stress testing (also known as forced degradation) of pharmaceutical drug substances and products is a critical part of the drug development process, providing insight into the degradation pathways of drug substances and drug products. This information is used to support the development of stability-indicating methods (SIMs) capable of detecting pharmaceutically relevant degradation products that might potentially be observed during manufacturing, long-term storage, distribution, and use. Assessing mass balance of stressed samples is a key aspect of developing SIMs and is a regulatory expectation. However, the approaches to measure, calculate, and interpret mass balance can vary among different pharmaceutical companies. Such disparities also pose difficulties for health authorities when reviewing mass balance assessments, which may result in the potential delay of drug application approvals. The authors have gathered input from 10 pharma companies to map out apractical review of science-based approaches and technical details to assess and interpret mass balance results. Key concepts of mass balance are introduced, various mass balance calculations are demonstrated, and recommendations on how to investigate poor mass balance results are presented using real-world case studies. Herein we provide a single source reference on the topic of mass balance in pharmaceutical forced degradation for small molecule drug substances and drug products in support of regulatory submissions with the goal of facilitating a shared understanding among pharmaceutical scientists and health authorities.

Microwave-Induced Synthesis of Bioactive Nitrogen Heterocycles.

There are many different applications of heterocyclic molecules in the pharmaceutical and materials science fields, which make them an important family of compounds. Among these heterocyclic compounds, nitrogen-containing heterocyclic (N-heterocyclic) compounds have attracted a lot of interest among researchers due to their various applications across a wide variety of fields. Many studies have been performed over the past few years to study the synthesis of N-heterocycles under different reaction conditions, such as solvent-free, catalytic, reactants immobilized on a solid support, one-pot synthesis, and microwave irradiation. It has been demonstrated by our research group that microwaves can be utilized for rapid and efficient synthesis of biologically active compounds. In this review, we provide an overview of the microwave-assisted non-catalytic and catalytic preparation of nitrogen-containing heterocycles, mostly polycyclic N-heterocycles, five-membered N-heterocycles, six-membered N-heterocycles, and fused N-heterocycles. Mostly in this article, we explore the microwave-assisted preparation of biologically important compounds, such as pyrimidines, thiazoles, imines, tetrazoles, steroidal derivatives, quinolines, indolizine, triazoles, beta-lactams, pyrroles and quinoxalines.

Artificial Intelligence: A Catalyst for Breakthroughs in Nanotechnology and Pharmaceutical Research

Artificial intelligence (AI) is revolutionizing nanotechnology and pharmaceutical research by streamlining drug discovery, optimizing formulations, and personalizing treatments through predictive modelling and data analysis. Without AI, the pharmaceutical industry requires more time due to less effective drug discovery, inefficient clinical trials, and prolonged regulatory processes, resulting in higher costs and delayed treatments1. The integration of AI with nanotechnology and pharmaceutical science is revolutionizing medicine, opening up new possibilities for diagnosis, treatment, and personalized healthcare. It also enhances clinical treatments and identifies new uses for existing drugs, reducing development time and costs2. By leveraging machine learning algorithms, researchers can predict the properties and behaviour of nanomaterials, facilitating the development of nanoparticles that can deliver drugs more efficiently to specific cells or tissues3. AI accelerates nano product development by optimizing nanomaterial design, predicting nanoparticle toxicity, and enhancing nanomedicine formulation. For example, AI has been used to design nanoparticles for targeted drug delivery, improving their efficiency and safety4. AI-enabled nanotechnology can enhance molecular profiling and early diagnosis, refine the design of nanomedicines, and improve their efficacy. By optimizing nanomedicine properties, achieving effective drug synergy, and reducing nanotoxicity, AI facilitates better targetability and accelerates the development of personalized treatments.

Rôle des médecins hospitalo-universitaires de médecine interne dans la formation aux métiers de la santé et au sein des institutions en France : enquête du Collège National des Enseignants de Médecine Interne (CEMI)

RationaleOn the occasion of the General stage meeting of Internal Medicine, the National College of Internal Medicine Teachers (CEMI) conducted a survey on teaching activity among all French university hospital (HU) internal medicine specialists. MethodThe survey was carried out in September 2023 by sending an email to 101 hospital practitioners university professors (PU–PH) and 18 hospital practitioners assistant professors (MCU–PH) of internal medicine in subsection 53-01 of the National council of universities (CNU), as well as to the 11 HU internists working in immunology (subsection 47-01) or therapeutics (subsection 48-04). ResultsSeventy-three HUs (56.1%) responded to the survey, including 65 PU–PH, 7 MCU–PH and 1 university hospital practitioner (PHU). Internal medicine HUs participate in faculty teaching: 80% are responsible for teaching, 30% are responsible for the year or cycle or lead committees and 40% have had or have an elected mandate at the faculty or at university. Internal medicine HU are involved in the teaching of semiology during the first cycle of medical studies, but also in pharmaceutical sciences, dentistry, midwifery and in paramedical training. They are very invested in the implementation of the second cycle reform and 80% are involved in the preparation of Objective Structured Clinical Examinations (ECOS), mainly as examiners (90%). They also participate in teaching using simulation (60%), teaching advanced practice nurses (IPA) (25%), and writing CEMI books (75%). For ECOS, 90% participate as examiners, 60% participate in teaching using simulation, 25% are involved in teaching advanced practice nurses (IPA), 75% participated in the writing of CEMI works. Eight (12%) internal medicine HUs co-facilitate training with patients and 26 (38%) participate in master's courses at the Faculty of Sciences. Finally, 94% are affiliated with a research unit and 48% supervise university theses students. ConclusionInternal medicine universities teachers have a strong educational commitment, particularly in semiology and in the reform of the second cycle of medical studies with ECOS and simulation.

Impact of Artificial Intelligence on Drug Development and Delivery.

This review explores the transformative impact of AI on drug development and delivery in pharmaceutical sciences, spanning formulation design, real-time monitoring, targeted delivery, and future prospects. The rational design of smart drug carriers, such as AI-optimized liposomes for cancer therapy, optimizes formulations for individual patient needs. AI-driven sensors, exemplified by glucose-monitoring biosensors for diabetics, enable adaptive drug administration, enhancing precision. Despite promises, challenges like biocompatibility, regulations, and ethics persist. Interdisciplinary collaboration and transparent communication are crucial for responsible AI adoption. Anticipated trends include personalized dosage optimization and intelligent nanocarriers. The review underscores AI's potential in reshaping pharmaceuticals for patient-centric care while addressing challenges for widespread adoption.

Skeletal Reorganization: Approaches Towards the Synthesis of Aza-heterocyclic Cores

The impetuous development of the pharmaceutical industry and material science stimulates the search for new synthetic approaches and new methods for the synthesis and functionalization of aza-heterocycles; these are some of the key objectives of modern organic chemistry. As a result of such, advanced method towards the synthesis of functionalized N-heterocycle that circumvents the limitations associated with traditional methods need to be devised. In recent decades, rearrangement/ reorganization reactions have emerged as a powerful tool for the efficient synthesis of the aza-heterocycle. In this illustration , we summarize some our recent efforts in the development of few complex aza heterocyclic cores.

The Revolutionary Role of Artificial Intelligence (AI) in Pharmaceutical Sciences

The Revolutionary Role of Artificial Intelligence (AI) in Pharmaceutical Sciences

Bilateral Unsymmetrical Disulfurating Reagent Design for Polysulfide Construction.

Polysulfides are significant compounds in life science, pharmaceutical science, and materials science. Therefore, polysulfide construction is in great demand. The controllable sequential installation of groups on both ends of a S-S motif faces an enormous challenge owing to the reversible nature of the covalent S-S bond. A library was established with two divergent mask groups for bilateral unsymmetrical disulfurating reagents (R1O-SS-SO2R2). Sequential coupling with preferential activation of the S-SO2 bond (37.6 kcal/mol) and controllable activation of the S-O bond (54.8 kcal/mol) in the presence of the S-S bond (62.0 kcal/mol) enabled successive reactions at each end of the S-S motif to afford unsymmetrical disulfides and trisulfides, even for the cross-linkage of natural products, pharmaceuticals, peptides, and a protein (bovine serum albumin).

Bilateral Unsymmetrical Disulfurating Reagent Design for Polysulfide Construction

AbstractPolysulfides are significant compounds in life science, pharmaceutical science, and materials science. Therefore, polysulfide construction is in great demand. The controllable sequential installation of groups on both ends of a S−S motif faces an enormous challenge owing to the reversible nature of the covalent S−S bond. A library was established with two divergent mask groups for bilateral unsymmetrical disulfurating reagents (R1O−SS−SO2R2). Sequential coupling with preferential activation of the S−SO2 bond (37.6 kcal/mol) and controllable activation of the S−O bond (54.8 kcal/mol) in the presence of the S−S bond (62.0 kcal/mol) enabled successive reactions at each end of the S−S motif to afford unsymmetrical disulfides and trisulfides, even for the cross‐linkage of natural products, pharmaceuticals, peptides, and a protein (bovine serum albumin).

Quaternary Ammonium Salts-Based Materials: A Review on Environmental Toxicity, Anti-Fouling Mechanisms and Applications in Marine and Water Treatment Industries.

The adherence of pathogenic microorganisms to surfaces and their association to form antibiotic-resistant biofilms threatens public health and affects several industrial sectors with significant economic losses. For this reason, the medical, pharmaceutical and materials science communities are exploring more effective anti-fouling approaches. This review focuses on the anti-fouling properties, structure-activity relationships and environmental toxicity of quaternary ammonium salts (QAS) and, as a subclass, ionic liquid compounds. Greener alternatives such as QAS-based antimicrobial polymers with biocide release, non-fouling (i.e., PEG, zwitterions), fouling release (i.e., poly(dimethylsiloxanes), fluorocarbon) and contact killing properties are highlighted. We also report on dual-functional polymers and stimuli-responsive materials. Given the economic and environmental impacts of biofilms in submerged surfaces, we emphasize the importance of less explored QAS-based anti-fouling approaches in the marine industry and in developing efficient membranes for water treatment systems.

Mixture Experimentation in Pharmaceutical Formulations: A Tutorial.

Mixture experimentation is commonly seen in pharmaceutical formulation studies, where the relative proportions of the individual components are modeled for effects on product attributes. The requirement that the sum of the component proportions equals 1 has given rise to the class of designs, known as mixture designs. The first mixture designs were published by Quenouille in 1953 but it took nearly 40 years for the earliest mixture design applications to be published in the pharmaceutical sciences literature by Kettaneh-Wold in 1991 and Waaler in 1992. Since then, the advent of efficient computer algorithms to generate designs has made this class of designs easily accessible to pharmaceutical statisticians, although the use of these designs appears to be an underutilized experimental strategy even today. One goal of this tutorial is to draw the attention of experimental statisticians to this class of designs and their advantages in pursuing formulation studies such as excipient compatibility studies. We present sufficient materials to introduce the novice practitioner to this class of design, associated models, and analysis strategies. An example of a mixture-process variable design is given as a case study.

Growth inhibition of P. aeruginosa by methanol extract of Bridelia stipularis and identification of active components using in silico studies

BackgroundAntimicrobial resistance among pathogens is an emerging problem, gaining significant importance recently. Pharmaceutical scientists are constantly exploring innovative and effective antibacterial agents. Pseudomonas aeruginosa (P. aeruginosa) is a bacterium primarily responsible for pneumonia and infections in the liver, kidneys, and other body parts. It is a Gram-negative bacterium that can be controlled by antibiotics such as ciprofloxacin and levofloxacin. However, this pathogen sometimes exhibits resistance to these antibacterial agents.MethodsRecognizing the well-known potential of plants as sources of medicinal compounds, our study focused on the ethyl acetate, acetone and methanol extract of the leaves of Bridelia stipularis and its impact on the growth of P. aeruginosa using well diffusion method. To gain insight into the composition of the extract, we conducted GC–MS analysis. After identifying the components present in the extract, we assessed the drug-likeness, absorption, distribution, metabolism, and excretion (ADME) and conducted docking studies of the molecules with the selected structural receptors of P. aeruginosa to find out the active component present in the extract.ResultsRemarkably, only methanol extract of Bridelia stipularis demonstrated significant antibacterial activity against this pathogen. In silico investigations revealed that two compounds, namely ethyl iso-allocholate and toluene sulfonylhydrazone derivative, exhibited high inhibition potencies. All structural receptors of the pathogen taken for this study were well inhibited by ethyl iso-allocholate while the receptors such as laconizing lipase and penicillin-binding protein of the bacterium were bound well with the 4-phenyl-3-penten-2-one p-toluene sulfonylhydrazone.ConclusionsObservations of this study clearly establish that the two phytochemicals present in the methanolic extract, i.e., ethyl iso-allocholate and toluene sulfonylhydrazone derivative of Bridelia stipularis leaves are highly active against the growth of the opportunistic pathogen P. aeruginosa.Graphical abstract

PH-responsive IPN beads of carboxymethyl konjac glucomannan and sodium carboxymethyl cellulose as a controlled release carrier for ibuprofen

The convergence of polymer and pharmaceutical sciences has advanced drug delivery systems significantly. Carbohydrate polymers, especially carboxymethylated ones, offer versatile benefits for pharmaceuticals. Interpenetrating polymer networks (IPNs) combine synthetic and natural polymers to enhance drug delivery. The study aims to develop IPN beads using sodium carboxymethyl cellulose (SCMC) and carboxymethyl konjac glucomannan (CMKGM) for controlled release of ibuprofen (IB) after oral administration. Objectives include formulation optimization, characterization of physicochemical properties, evaluation of pH-dependent swelling and drug release behaviors to advance biocompatible and efficient oral drug delivery systems. The beads were analyzed using SEM, FTIR, DSC, and XRD techniques. Different ratio of polymers (CMKGM:SCMS) and crosslinker concentrations (2&4 %w/v) were used, significantly impacting bead size, swelling, drug encapsulation, and release characteristics. DSC results indicated higher thermal stability in IPN beads compared to native polymers. XRD revealed IB dispersion within the polymer matrix. IPN beads size ranged from 580 ± 0.56 to 324 ± 0.27 μm, with a nearly spherical shape. IPN beads exhibited continuous release in alkaline conditions (pH 7.4) and minimal release in acidic media (pH 1.2). These findings suggest that the formulated IPN beads can modulate drug release in both acidic and alkaline environments, potentially mitigating the gastric adverse effects often associated with oral administration of IB.

The Golden Spice for Life: Turmeric with the Pharmacological Benefits of Curcuminoids Components, Including Curcumin, Bisdemethoxycurcumin, and Demethoxycurcumins.

Turmeric (Curcuma longa L.), belonging to the Zingiberaceae family, is a perennial rhizomatous plant of tropical and subtropical regions. The three major chemical components responsible for the biological activities of turmeric are curcumin, demethoxycurcumin, and bisdemethoxycurcumin. The literature search included review articles, analytical studies, randomized control experiments, and observations, which have been gathered from various sources, such as Scopus, Google Scholar, PubMed, and ScienceDirect. A review of the literature was carried out using the keywords: turmeric, traditional Chinese medicine, traditional Iranian medicine, traditional Indian medicine, curcumin, curcuminoids, pharmaceutical benefits, turmerone, demethoxycurcumin, and bisdemethoxycurcumin. The main components of the rhizome of the leaf are α-turmerone, β-turmerone, and arturmerone. The notable health benefits of turmeric are antioxidant activity, gastrointestinal effects, anticancer effects, cardiovascular and antidiabetic effects, antimicrobial activity, photoprotector activity, hepatoprotective and renoprotective effects, and appropriate for the treatment of Alzheimer's disease and inflammatory and edematic disorders. Curcuminoids are phenolic compounds usually used as pigment spices with many health benefits, such as antiviral, antitumour, anti-HIV, anti-inflammatory, antiparasitic, anticancer, and antifungal effects. Curcumin, bisdemethoxycurcumin, and demethoxycurcumin are the major active and stable bioactive constituents of curcuminoids. Curcumin, which is a hydroponic polyphenol, and the main coloring agent in the rhizomes of turmeric, has anti-inflammatory, antioxidant, anti-cancer, and anticarcinogenic activities, as well as beneficial effects for infectious diseases and Alzheimer's disease. Bisdemethoxycurcumin possesses antioxidant, anti-cancer, and anti-metastasis activities. Demethoxycurcumin, which is another major component, has anti-inflammatory, antiproliferative, and anti-cancer activities and is the appropriate candidate for the treatment of Alzheimer's disease. The goal of this review is to highlight the health benefits of turmeric in both traditional and modern pharmaceutical sciences by considering the important roles of curcuminoids and other major chemical constituents of turmeric.

A Review of the Latest Spectroscopic Research in Pharmaceutical and Biopharmaceutical Applications

Spectroscopic analytical techniques are pivotal in the pharmaceutical and biopharmaceutical industries, facilitating the classification and quantification of processes and products. This review highlights very recent advancements in several key spectroscopic methods, including atomic, vibrational, molecular, electronic, and diffraction techniques. The applications of these analytical techniques in drug development, process monitoring, and quality control are discussed, showcasing their integral roles in advancing pharmaceutical sciences.

IMSIS: An instrumented microphysiological system with integrated sensors for monitoring cellular metabolic activities

Well plates are widely used in biological experiments, particularly in pharmaceutical sciences and cell biology. Its popularity stems from its versatility to support a variety of fluorescent markers for high throughput monitoring of cellular activities. However, using fluorescent markers in traditional well plates has its own challenges, namely, they can be potentially toxic to cells, and thus, may perturb their biological functions; and it is difficult to monitor multiple analytes concurrently and in real-time inside each well. This paper presents a fully instrumented microphysiological system with integrated sensors (IMSIS) with a similar well format. Each well in the microphysiological system has a set of sensors for monitoring multiple metabolic analytes in real-time. The IMSIS platform is supported by integrated bioelectronic circuits and a graphical user interface for easy user configuration and monitoring. The system has integrated microfluidics to maintain its microphysiological environment within each well. The IMSIS platform currently incorporates O2, H2O2, and pH sensors inside each well, allowing up to six wells to perform concurrent measurements in real-time. Furthermore, the architecture is scalable to achieve an even higher level of throughput. The miniaturized design ensures portability, suitable for small offices and field applications.The IMSIS platform was successfully used to monitor in real-time the mitochondrial functions of live bovine embryos in O2 consumption, H2O2 release as an indication of ROS production, and extracellular acidity changes before and after the introduction of external substrates.

Recent Advances in Catalytic Desymmetrization for the Synthesis of Axially Chiral Biaryls

AbstractAtropisomeric compounds have been discovered in pharmaceuticals and materials science, and their enantioselective syntheses have gained tremendous attention. Among strategies for catalytic atroposelective synthesis, desymmetrization provides robust and straightforward approaches to axially chiral biaryls. Due to the relative ease of substrate design compared to other atroposelective strategies, desymmetrization has emerged as a pivotal stage for converting fascinating chemistry into its atroposelective counterpart, despite challenges such as the formation of achiral products by subsequent catalytic reactions and the long distance between the reaction site and the stereogenic axis. This review offers a comprehensive overview of recent advancements in atroposelective desymmetrization using chiral organo‐ and metal catalysts, addressing challenges and solutions, and aims to provide insights into future developments in this field.