Pharmaceutical Drug Development Research Articles

Critical View on the Qualification of Electronic Tongues Regarding Their Performance in the Development of Peroral Drug Formulations with Bitter Ingredients.

In this review, we aim to highlight the advantages, challenges, and limitations of electronic tongues (e-tongues) in pharmaceutical drug development. The authors, therefore, critically evaluated the performance of e-tongues regarding their qualification to assess peroral formulations containing bitter active pharmaceutical ingredients. A literature search using the keywords 'electronic', 'tongue', 'bitter', and 'drug' in a Web of Science search was therefore initially conducted. Reviewing the publications of the past decade, and further literature where necessary, allowed the authors to discuss whether and how e-tongues perform as expected and whether they have the potential to become a standard tool in drug development. Specifically highlighted are the expectations an e-tongue should meet. Further, a brief insight into the technologies of the utilized e-tongues is given. Reliable protocols were found that enable (i) the qualified performance of e-tongue instruments from an analytical perspective, (ii) proper taste-masking assessments, and (iii) under certain circumstances, the evaluation of bitterness.

ASPECTS OF THE USE OF ANTIDIABETIC DRUGS IN PHARMACEUTICAL PRACTICE ON THE BASIS OF RATIONAL PHARMACOTHERAPY

The aim of the article. To study of the incidence of diabetes mellitus in Ukraine and to determine the prospects for the use and pharmaceutical development of antidiabetic drugs. Materials and methods. Data from the State Registers of Medicinal Products of Ukraine, of Wholesale and Retail Prices for Medicinal Products declared in Ukraine under an international non-proprietary or generic name (01.01.2024). Were used: systematic and comparative analysis, processing and synthesis, and generalization to determine the forecasted prospects. Results. In Ukraine the number of diabetes patients increased by 11% in the group of children and adolescents; in the group of elderly patients – by 12.5%, among the adult working – 20%, diabetes of the II type predominates. The trend of increase in the number of studies on the search for therapeutic alternatives for the treatment of type II diabetes and list of medicines on the pharmaceutical market has been revealed. In Ukraine drugs for oral use include APIs of the following pharmacological groups: sulfonylureas; meglitinides; biguanides; thiazolidinedione; α-glucosidase inhibitors; DPP-4 inhibitors; SGLT-2 inhibitors. Mechanism of action of the new class of oral hypoglycemic agents, approved by the FDA, consists in blocking SGLT-2 proteins from the proximal convoluted tubule in the kidney, leads to the prevention of reabsorption and excretion of the glucose molecule. This allows its use in combination with insulin and other antidiabetic drugs for the treatment of type I and II diabetes in patients of various age categories. According to the volume of clinical studies, SGLT-2 inhibitor SGLT-2 derivative gliflozin API drugs are the second largest group of antidiabetic drugs recommended for use by FDA and EMA regulatory bodies. Conclusions. The pharmaceutical development of mono and combined drugs with APIs SGLT-2 inhibitors gliflozin derivatives in combination with APIs with metformin, DPP-4 inhibitors, APIs thiazolidinedione derivatives is promising for solving the problem of diabetes treatment and prevention of complications for patients of different age groups including working population in Ukraine.

Enhancing drug development and clinical studies with patient-centric sampling using microsampling techniques: Opportunities, challenges, and insights into liquid chromatography-mass spectrometrystrategies.

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient-centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography-mass spectrometry (LC-MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient-centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy.

Musculoskeletal Health Systematic Review: Clinical and Pharmacological, Organizational and Legal, Administration and Pharmaceutical Management Aspects

This article examines current aspects of musculoskeletal health and pharmacotherapy of disorders of the human musculoskeletal system. An objective review of disorders of the musculoskeletal system was conducted in the areas of administration, clinical and pharmacological, organizational and legal, pharmaceutical management. The results of the systematic review show that the availability of diagnoses in the section "Orthopedics and traumatology" on the platform of the state expert center of the Ministry of Health of Ukraine is limited. It is necessary and urgent to expand the scientific base for practicing doctors. The study confirmed the importance of using new clinical protocols in medical and pharmaceutical practice for the implementation of evidence-based medicine and evidence-based pharmacy in Ukraine. Gradual improvement of medical and pharmaceutical practice allows to increase the quality, efficiency, safety, availability of pharmacotherapy for patients with disorders of the musculoskeletal system. The paper examines guidelines developed on the basis of health evidence provided by Duodecim Medical Publications. The study shows the availability of a wide range of treatment methods and helps to determine optimal therapy strategies in the field of orthopedics. It was found that non-steroidal anti-inflammatory drugs and analgesics are more often prescribed for the pharmacotherapy of disorders of the musculoskeletal system, which emphasizes the perspective of further clinical and pharmacological, organizational and legal researches in the pharmaceutical development and management of new drugs.

A model design for managing technological parameters at the stage of the pharmaceutical development of antidiabetic drugs in the form of solid dosage forms

Aim. To develop a model for managing technological parameters at the stage of the pharmaceutical development of an antidiabetic drug in tablets with API of SGLT-2 class – a derivative of gliflozin. Materials and methods. In the study conducted, the methods of system and comparative analysis, generalization, statistical processing and synthesis were used in determining the projected prospects, design, modeling, mathematical modeling, tabular and graphic means of presenting the results. To implement the goals and objectives of the study, software and electronic resources of the Anatomical Therapeutically Chemical Classification System (ATC), Biopharmaceutical Classification System (BCS), Compendium, State Register of Medicines of Ukraine were used; statistical data and data from clinical studies of the content were as follows: https://www.wipo.int; https://www.dec.gov.ua; https://www.clinicaltrials.gov; https://www.ncbi.nlm. nih.gov; https://eacpt.org; https://bpspubs.onlinelibrary.wiley.com. The study was conducted on the modern equipment for determining the bulk density (ERWEKA SVM 202, Germany), the flowability of powders (ERWEKA GT, Germany), resistance to crushing (ERWEKA TBH-525 WTO, Germany), friability (ERWEKA TAR 200, Germany), disintegration (ERWEKA ZT 33, Germany). The active ingredient in tablets of the antidiabetic drug is API calculated with reference to the content of dapagliflozin, 5 mg. The following excipients from the groups of fillers (factor A) were used: a1 – microcrystalline cellulose (MCC) of grade 200, a2 – lactose monohydrate of grade 80, a3 – a mixture of MCC of grade 102 with anhydrous lactose of grade 22 AN in the ratio of 3:1; disintegrants (factor B): b1 – crospovidone XL-10, b2 – sodium croscarmellose, b3 – sodium starch glycolate, glidants (factor C): c1 – colloidal anhydrous silicon dioxide (aerosil 200), c2 – talc, c3 – polyethylene glycol (PEG) 8000, as well as magnesium stearate as a lubricant. The experimental data were subjected to statistical processing by the method of variance analysis. Results and discussion. The development and introduction of new pharmaceuticals, effective analogs and generics is an important task as it contributes to the improvement of the quality of drug supply, treatment and safe use for patients with diabetes mellitus. A model for managing technological parameters at the stage of the pharmaceutical development has been developed; the target quality profile of the antidiabetic drug and tablets with API of SGLT-2 class – a derivative of gliflozin has been substantiated, and critical quality indicators have been determined. According to the model proposed, the optimal composition and technology of antidiabetic tablets with API of SGLT-2 class – a derivative of gliflozin calculated with reference to dapagliflozin, 5 mg, have been developed using an experiment planning matrix based on a 3*3 hyper-Greek-Latin square of the second order; the excipients have been selected; the effect of qualitative and quantitative factors and technological parameters on the pharmaco-technological properties of the tablet masses studied and tablet quality indicators, as well as critical indicators of the quality of the pharmaceutical product have been determined. Experimental studies and risk assessment have been carried out; based on the results, the optimal parameters of the technological process for the production of the antidiabetic drug in tablets with API of SGLT-2 class – a derivative of gliflozin – dapagliflozin have been substantiated. Conclusions. Based on the results of the system analysis of the application of mathematical models in the production of pharmaceutical forms, it has been determined that mathematical modeling is a key stage for ensuring the quality of the technological process at the stage of the pharmaceutical development of an antidiabetic drug in tablets with API of SGLT-2 class – a derivative of gliflozin. The use of mathematical modeling in the course of the pharmaceutical development allows optimization at the stage of the experimental research of API, its polymorphic form, physico-chemical properties and pharmaco-technological indicators. A model for managing technological parameters at the stage of the pharmaceutical development has been proposed; the target quality profile of the antidiabetic drug and tablets with API of SGLT-2 class – a derivative of gliflozin has been substantiated; the optimal composition and technology of this pharmaceutical product has been developed.

Pediatric Formulations Developed by Extrusion-Based 3D Printing: From Past Discoveries to Future Prospects.

Three-dimensional printing (3DP) technology in pharmaceutical areas is leading to a significant change in controlled drug delivery and pharmaceutical product development. Pharmaceutical industries and academics are becoming increasingly interested in this innovative technology due to its inherent inexpensiveness and rapid prototyping. The 3DP process could be established in the pharmaceutical industry to replace conventional large-scale manufacturing processes, particularly useful for personalizing pediatric drugs. For instance, shape, size, dosage, drug release and multi-drug combinations can be tailored according to the patient's needs. Pediatric drug development has a significant global impact due to the growing needs for accessible age-appropriate pediatric medicines and for acceptable drug products to ensure adherence to the prescribed treatment. Three-dimensional printing offers several significant advantages for clinical pharmaceutical drug development, such as the ability to personalize medicines, speed up drug manufacturing timelines and provide on-demand drugs in hospitals and pharmacies. The aim of this article is to highlight the benefits of extrusion-based 3D printing technology. The future potential of 3DP in pharmaceuticals has been widely shown in the last few years. This article summarizes the discoveries about pediatric pharmaceutical formulations which have been developed with extrusion-based technologies.

Natural products of plant origin: an emerging therapeutic for dermatomycosis.

Dermatomycosis or superficial mycosis is considered one of the chronic fungal infections and a global challenge for the public health system. The severity of dermatomycosis is proportionately increasing with the emerging population of immunocompromised individuals, and it is becoming more prevalent, even life-threatening, in several tropical countries. In this context, improper long-term treatment with synthetic antifungal drugs and their related side effects imposes additional challenges in treating dermatomycosis. Thus, the present scenario highlights the need for a novel and accurate treatment with minimal or no side effects. The multifaceted therapeutic properties of various natural products have garnered the interest of scientific communities in recent years. Generally, plant-based products have low toxicity levels and offer diverse formulations and unique biomolecules for clinical applicability against dermatomycosis. Thus, this study presents an overview of the pathogenesis and different treatment strategies for dermatomycosis. In addition, we highlight the implementation of natural products of plant origin for treating dermatomycosis infections and reducing adverse events. Further, their mode of action and role in the development of pharmaceutical drugs are discussed.

Finding Creativity in Predictability: Seizing Kairos in Chronos Through Temporal Work in Complex Innovation Processes

Managing temporal complexity is a fundamental challenge in complex innovation processes, yet the temporal work whereby actors seize opportune moments (kairos) in an environment dominated by clock-time structures (chronos) remains elusive. Temporal tensions can partly be resolved through entrainment, that is, by aligning activities with dominant temporal structures. However, although entrainment ensures the exploitation of a predefined path, it is unable to harness unexpected developments as opportunities for exploration. Thus, navigating the competing temporal demands of chronos and kairos requires not just ambidextrous but also ambitemporal organizing. Collecting and analyzing in-depth interview and observational data from pharmaceutical drug discovery and development, we find that actors sometimes resolve temporal tensions through entrainment to ensure coordination and predictability. In other instances, however, actors abductively transform temporal tensions into novel interpretations and new courses of action. As such, temporal tensions become more than a bothersome deviation from the planned schedule, but an opportunity for creative agency. This understanding of kairos—as a process unfolding through temporal work—relies not only on detraining from chronos (i.e., momentarily detaching from the dominant temporal structure to question underlying assumptions), but also on its reframing and reconfiguration. We contribute to the literature on complex innovation and temporality by theorizing a transformative perspective on ambitemporal organizing, which relies less on paradoxical notions and instead emphasizes how kairos is enacted and seized within and from chronos. Funding: This work was supported by German Research Foundation (DFG) funding for the Research Unit “Organized Creativity” [Grant FOR 2161] as well as by the Austrian Science Fund (FWF) [10.55776/I4884].

Exploring the essence of celery seeds (Apium graveolens L.): Innovations in microwave-assisted hydrodistillation for essential oil extraction using in vitro, in vivo and in silico studies

This study presents the composition analysis of essential oils extracted from celery seeds (Apium graveolens L.) collected from Morocco. Essential oil of A. graveolens (AG-EO), were obtained through microwave-assisted hydro-distillation, and its composition was characterized using gas chromatography/mass spectrometry (GC/MS). antimicrobial properties were assessed utilizing disc diffusion and microdilution assay methods, while antioxidant activities were evaluated through spectrophotometric techniques. Additionally, in vivo anti-inflammatory effects were investigated. The molecular docking technique, a computational approach utilized to predict the binding of small molecules to specific proteins, was employed to elucidate the antioxidative and antibacterial characteristics of the constituent molecules. The physicochemical and pharmacokinetic features of absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) tests were anticipated to provide insights into the drug likeness, pharmacokinetic characteristics, and expected safety profiles upon ingestion and the potential pharmacological activity of the identified compounds. Fifteen constituent compounds representing 99.99% of AG-EO were identified and quantified by the use of GC/MS. The main constituent, comprising 64.58% of AG-EO was limonene. AG-EO demonstrated a significant DPPH free radical scavenging activity, showing estimated scavenging rates of 8.49±0.00 µg/mL, and 5.09±0.04 µg/mL for ABTS+. AG-EO exhibited reducing Power (RP) and total antioxidant activity (TAC) of 3.42±0.01 µg/mL and 245.93±0.04 mg AAE/mL, respectively. AG-EO exhibited significant antimicrobial activity against all tested microorganisms. Additionally, the anti-inflammatory activity demonstrated the remarkable efficacy of AG-EO. Taken together, the essential oil derived from celery seeds holds promise for large-scale utilization as an environmentally friendly preservative within the food and agriculture industries, effectively countering fungal growth and aflatoxin contamination in stored commodities. Additionally, it exhibits potential as a suitable candidate for the development of pharmaceutical drugs.

Using Social Media as a Source of Real-World Data for Pharmaceutical Drug Development and Regulatory Decision Making.

While pharmaceutical companies aim to leverage real-world data (RWD) to bridge the gap between clinical drug development and real-world patient outcomes, extant research has mainly focused on the use of social media in a post-approval safety-surveillance setting. Recent regulatory and technological developments indicate that social media may serve as a rich source to expand the evidence base to pre-approval and drug development activities. However, use cases related to drug development have been largely omitted, thereby missing some of the benefits of RWD. In addition, an applied end-to-end understanding of RWD rooted in both industry and regulations is lacking. We aimed to investigate how social media can be used as a source of RWD to support regulatory decision making and drug development in the pharmaceutical industry. We aimed to specifically explore the data pipeline and examine how social-media derived RWD can align with regulatory guidance from the US Food and Drug Administration and industry needs. A machine learning pipeline was developed to extract patient insights related to anticoagulants from X (Twitter) data. These findings were then analysed from an industry perspective, and complemented by interviews with professionals from a pharmaceutical company. The analysis reveals several use cases where RWD derived from social media can be beneficial, particularly in generating hypotheses around patient and therapeutic area needs. We also note certain limitations of social media data, particularly around inferring causality. Social media display considerable potential as a source of RWD for guiding efforts in pharmaceutical drug development and pre-approval settings. Although further regulatory guidance on the use of social media for RWD is needed to encourage its use, regulatory and technological developments are suggested to warrant at least exploratory uses for drug development.

Nanorobotics: Pioneering Drug Delivery and Development in Pharmaceuticals

Nanorobotics, a rapidly evolving field at the intersection of nanotechnology and robotics, holds immense promise in revolutionizing pharmaceutical drug delivery and development. This comprehensive review article explores the various facets of nanorobotics and its pivotal role in the advancement of medicine. The article begins with an introduction to nanorobotics, providing a definition and historical background to contextualize its significance. Subsequently, it delves into nanorobotics' role in drug delivery, highlighting the challenges faced in conventional methods and the advantages of employing nanorobot-based systems. The review further explores nanorobotics in drug development, emphasizing its contribution to accelerating drug discovery and enabling personalized medicine. It discusses the different types of nanorobots utilized in pharmaceutical applications, including molecular, cellular, and hybrid systems. Additionally, the article covers the fabrication and propulsion techniques of nanorobots, along with navigation and control strategies. Furthermore, it delves into the interaction of nanorobots with biological systems and their potential applications in site-specific drug delivery and disease treatment. Ethical and regulatory considerations pertinent to nanorobotics in pharmaceuticals are also addressed. Finally, the review offers insights into future perspectives and challenges in the field, envisioning advanced drug delivery systems, targeted therapies, nanorobot swarms, and biohybrids. By comprehensively examining the subject, this review article presents a holistic understanding of nanorobotics potential in reshaping pharmaceutical practices for precision medicine and improved patient outcomes.

PHARMACOINFORMATICS ANALYSIS OF MORUS MACROURA FOR DRUG DISCOVERY AND DEVELOPMENT

Objective: Pharmacoinformatics is an innovative approach rapidly evolving in pharmaceutical research and drug development. This study focuses on analysing Morus macroura, a plant species with untapped pharmacological potential. This investigation aims to leverage pharmacoinformatics techniques to unveil the hidden potential of Morus macroura in drug discovery and development.
 Methods: The study includes analyses of protein-protein interactions, deep learning docking, adsorption tests, distribution, metabolism, excretion, molecular dynamics simulations and free energy calculation using Molecular Mechanics Generalized Born Surface Area (MMGBSA).
 Results: Nine active compounds were identified in Morus macroura, namely Andalasin A, Guangsangon K, Guangsangon L, Guangsangon M, Guangsangon N, Macrourone C, Mulberrofuran G, Mulberrofuran K, and Mulberroside C. These compounds exhibit protein-protein interaction activities against a cytochrome P450 monooxygenase that catalyses the conversion of C19 androgens. These plant compounds influence aromatase excess syndrome, deficiency, and ovarian dysgenesis. Regarding drug-likeness, Mulberroside C and Macrourone C demonstrated good absorption potential by adhering to Lipinski's rule of five. Deep learning docking simulations yielded affinity results of-9.62 kcal/mol for Guangsangon M,-10.44 kcal/mol for Macrourone C, and-10.99 kcal/mol for Guangsangon L. Subsequent molecular dynamics simulations indicated that Guangsangon L and Macrourone C remained stable during a 100 ns simulation.
 Conclusion: Morus macroura interacts with important proteins, particularly CYP19A1, which might influence health conditions like aromatase excess syndrome and ovarian dysgenesis. These findings provide potential paths for addressing specific health issues and advancing drug development. Molecular dynamics simulations indicated that Guangsangon L and Macrourone C remained stable during simulation.

A Multi-Objective Approach Optimizing Pharmacy Industry Decisions through MOORA Method

The pharmacy industry, a crucial pillar of the healthcare sector, encompasses the discovery, development, production, distribution, and sale of pharmaceutical drugs and medications. With an intricate interplay of scientific innovation, medical expertise, and commercial activities, this industry plays an indispensable role in safeguarding and improving human health. From the inception of groundbreaking drugs to their widespread distribution, the pharmacy industry integrates various stakeholders, including pharmaceutical companies, researchers, healthcare professionals, regulators, and consumers. It strives to address a wide spectrum of health conditions, from acute ailments to chronic diseases, by developing innovative treatments, generic medicines, and over-the-counter drugs. The pharmacy industry's evolution has been marked by technological advancements, research breakthroughs, and regulatory frameworks to ensure drug safety and efficacy. As the global population continues to grow and age, the industry faces the challenges of maintaining affordability, accessibility, and quality of medications. Furthermore, the pharmacy industry is a catalyst for economic growth, creating jobs, fostering research collaborations, and contributing to national and international healthcare systems. Its multifaceted nature, ranging from drug research to patient care, underscores its significance in the broader landscape of healthcare and public well-being. Research within the pharmacy industry holds immense significance due to its pivotal role in advancing medical knowledge and improving patient outcomes. Pharmaceutical research drives the development of new medications, innovative therapies, and treatment protocols, enhancing the efficacy and safety of drugs. It also uncovers insights into disease mechanisms, fostering a deeper understanding of health conditions. Furthermore, research guides regulatory decisions, ensuring drugs' quality, and promotes evidence-based medical practices. Through ongoing investigation, the pharmacy industry continually evolves, addressing emerging health challenges, optimizing drug utilization, and ultimately contributing to the overall enhancement of global healthcare standards. MOORA (Multi-Objective Optimization by Ratio Analysis) is a decision-making method used to evaluate and prioritize alternatives based on multiple conflicting criteria. It involves comparing alternatives' performance ratios against reference alternatives, considering both benefits and drawbacks. By assigning weights to criteria, MOORA quantifies their importance and ranks alternatives accordingly. This technique assists in complex decision scenarios where various factors must be balanced. MOORA's systematic approach aids in reaching well-informed decisions by quantifying trade-offs and providing a structured framework for considering multiple objectives simultaneously. Product Innovation, Market Share (%), Research Investment ($ billion), Patient Satisfaction, Drug Efficacy (%), Global Reach (countries). Pfizer, Johnson & Johnson, Roche, Novartis, GlaxoSmithKline, CVS Health, Walgreens Boots Alliance, Rite Aid.From the result it is seen that Novartisis got the first rank where as is the Rite Aidis having the lowest rank.

In Vitro and In Vivo Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles.

RNA therapeutics has advanced into the third milestone in pharmaceutical drug development, following chemical and protein therapeutics. RNA itself can serve as therapeutics, carriers, regulators, or substrates in drug development. Due to RNA's motile, dynamic, and deformable properties, RNA nanoparticles have demonstrated spontaneous targeting and accumulation in cancer vasculature and fast excretion through the kidney glomerulus to urine to prevent possible interactions with healthy organs. Furthermore, the negatively charged phosphate backbone of RNA results in general repulsion from negatively charged lipid cell membranes for further avoidance of vital organs. Thus, RNA nanoparticles can spontaneously enrich tumor vasculature and efficiently enter tumor cells via specific targeting, while those not entering the tumor tissue will clear from the body quickly. These favorable parameters have led to the expectation that RNA has low or little toxicity. RNA nanoparticles have been well characterized for their anticancer efficacy; however, little detail on RNA nanoparticle pathology and safety is known. Here, we report the in vitro and in vivo assessment of the pathology and safety aspects of different RNA nanoparticles including RNA three-way junction (3WJ) harboring 2'-F modified pyrimidine, folic acid, and Survivin siRNA, as well as the RNA four-way junction (4WJ) harboring 2'-F modified pyrimidine and 24 copies of SN38. Both animal models and patient serum were investigated. In vitro studies include hemolysis, platelet aggregation, complement activation, plasma coagulation, and interferon induction. In vivo studies include hematoxylin and eosin (H&E) staining, hematological and biochemical analysis as the serum profiling, and animal organ weight study. No significant toxicity, side effect, or immune responses were detected during the extensive safety evaluations of RNA nanoparticles. These results further complement previous cancer inhibition studies and demonstrate RNA nanoparticles as an effective and safe drug delivery vehicle for future clinical translations.

From Ocean to Medicine: Harnessing Seaweed's Potential for Drug Development.

Seaweed, a miscellaneous group of marine algae, has long been recognized for its rich nutritional composition and bioactive compounds, being considered nutraceutical ingredient. This revision delves into the promising role of seaweed-derived nutrients as a beneficial resource for drug discovery and innovative product development. Seaweeds are abundant sources of essential vitamins, minerals, polysaccharides, polyphenols, and unique secondary metabolites, which reveal a wide range of biological activities. These bioactive compounds possess potential therapeutic properties, making them intriguing candidates for drug leads in various medical applications and pharmaceutical drug development. It explores their pharmacological properties, including antioxidant, anti-inflammatory, antimicrobial, and anticancer activities, shedding light on their potential as therapeutic agents. Moreover, the manuscript provides insights into the development of formulation strategies and delivery systems to enhance the bioavailability and stability of seaweed-derived compounds. The manuscript also discusses the challenges and opportunities associated with the integration of seaweed-based nutrients into the pharmaceutical and nutraceutical industries. Regulatory considerations, sustainability, and scalability of sustainable seaweed sourcing and cultivation methods are addressed, emphasizing the need for a holistic approach in harnessing seaweed's potential. This revision underscores the immense potential of seaweed-derived compounds as a valuable reservoir for drug leads and product development. By bridging the gap between marine biology, pharmacology, and product formulation, this research contributes to the critical advancement of sustainable and innovative solutions in the pharmaceutical and nutraceutical sectors.

Failing Fast in New Pharmaceutical Drug Development

Failing Fast in New Pharmaceutical Drug Development

Exploring the Evolution of Analytical Method Validation: Current Perspectives

In this review, we delve into the critical process of analytical method development and validation within the realm of pharmaceutical drug development. The creation of sound analytical methods stands as a cornerstone from the early stages of drug discovery through to the eventual marketing approval. Our objective is to meticulously examine the methodology behind developing, optimizing, and validating analytical methods, particularly focusing on their application to drug products – from the formulation's developmental stage to the production of commercial batches. We begin by elucidating the significance of method development tailored to the specific components of finished drug products or in-process tests. Additionally, we delve into the intricacies of sample preparation techniques essential for accurate analysis. Central to our discussion are the practical approaches employed to ascertain critical parameters including selectivity, specificity, limit of detection, limit of quantitation, linearity, range accuracy, precision, recovery, solution stability, ruggedness, and robustness of liquid chromatographic methods. These parameters are indispensable for supporting routine, in-process, and stability analyses crucial for ensuring the safety, efficacy, and quality of pharmaceutical products. By dissecting the intricacies of method development and validation, this review aims to provide pharmaceutical researchers and practitioners with valuable insights and practical guidelines to navigate the complex landscape of analytical method validation in drug development.

RNA four-way junction (4WJ) for spontaneous cancer-targeting, effective tumor-regression, metastasis suppression, fast renal excretion and undetectable toxicity

The field of RNA therapeutics has been emerging as the third milestone in pharmaceutical drug development. RNA nanoparticles have displayed motile and deformable properties to allow for high tumor accumulation with undetectable healthy organ accumulation. Therefore, RNA nanoparticles have the potential to serve as potent drug delivery vehicles with strong anti-cancer responses. Herein, we report the physicochemical basis for the rational design of a branched RNA four-way junction (4WJ) nanoparticle that results in advantageous high-thermostability and -drug payload for cancer therapy, including metastatic tumors in the lung. The 4WJ nanostructure displayed versatility through functionalization with an anti-cancer chemical drug, SN38, for the treatment of two different cancer models including colorectal cancer xenograft and orthotopic lung metastases of colon cancer. The resulting 4WJ RNA drug complex spontaneously targeted cancers effectively for cancer inhibition with and without ligands. The 4WJ displayed fast renal excretion, rapid body clearance, and little organ accumulation with undetectable toxicity and immunogenicity. The safety parameters were documented by organ histology, blood biochemistry, and pathological analysis. The highly efficient cancer inhibition, undetectable drug toxicity, and favorable Chemical, Manufacturing, and Control (CMC) production of RNA nanoparticles document a candidate with high potential for translation in cancer therapy.

New Perspectives for Antihypertensive Sartans as Components of Co-crystals and Co-amorphous Solids with Improved Properties and Multipurpose Activity.

Sartans (angiotensin II receptor blockers, ARBs), drugs used in the treatment of hypertension, play a principal role in addressing the global health challenge of hypertension. In the past three years, their potential use has expanded to include the possibility of their application in the treatment of COVID-19 and neurodegenerative diseases (80 clinical studies worldwide). However, their therapeutic efficacy is limited by their poor solubility and bioavailability, prompting the need for innovative approaches to improve their pharmaceutical properties. This review discusses methods of co-crystallization and co-amorphization of sartans with nonpolymeric, low molecular, and stabilizing co-formers, as a promising strategy to synthesize new multipurpose drugs with enhanced pharmaceutical properties. The solid-state forms have demonstrated the potential to address the poor solubility limitations of conventional sartan formulations and offer new opportunities to develop dual-active drugs with broader therapeutic applications. The review includes an in-depth analysis of the co-crystal and co-amorphous forms of sartans, including their properties, possible applications, and the impact of synthetic methods on their pharmacokinetic properties. By shedding light on the solid forms of sartans, this article provides valuable insights into their potential as improved drug formulations. Moreover, this review may serve as a valuable resource for designing similar solid forms of sartans and other drugs, fostering further advances in pharmaceutical research and drug development.

Antibody Profiling: Kinetics with Native Biomarkers for Diagnostic Assay and Drug Developments.

Despite remarkable progress in applied Surface Plasmon Resonance (SPR)-based methods, concise monitoring of kinetic properties for native biomarkers from patient samples is still lacking. Not only are low concentrations of native targets in patient samples, often in the pM range, a limiting and challenging factor, but body fluids as complex matrices furthermore complicate measurements. The here-described method enables the determination of kinetic constants and resulting affinities for native antigens from patients' cerebrospinal fluid (CSF) and sera binding to antibodies. Using a significantly extended target-enrichment step, we modified a common sandwich-assay protocol, based on a primary and secondary antibody. We successfully analyze antibody kinetics of native targets from a variety of origins, with consistent results, independent of their source. Moreover, native neurofilament light chain (NFL) was investigated as an exemplary biomarker. Obtained data reveal antibodies recognizing recombinant NFL with high affinities, while showing no, or only significantly weakened binding to native NFL. The indicated differences for recombinant vs. native material demonstrate another beneficial application. Our assay is highly suitable for gaining valuable insights into characteristics of native biomarkers, thus impacting on the binder development of diagnostic reagents or pharmaceutical drugs.