Search Results (1,205)

Therapeutic glycoproteins, a pivotal class of biopharmaceuticals, have transformed modern medicine through their broad applications in oncology, immunotherapy, and infectious disease management. Their structural complexity and biological specificity make them highly effective in targeting disease pathways; however, challenges related to stability, bioavailability, and delivery efficacy limit their full potential. Recent advancements in delivery technologies have sought to address these challenges through innovative approaches such as nanotechnology-based carriers, controlled-release systems, and molecular engineering. These strategies have demonstrated the ability to enhance glycoprotein stability, optimize pharmacokinetics, and achieve targeted delivery with minimal off-target effects. This review provides a comprehensive overview of state-of-the-art lipid-based delivery systems specifically designed to overcome the unique pharmaceutical challenges associated with therapeutic glycoproteins, highlighting their design principles, formulation strategies, mechanisms of encapsulation and release, and therapeutic advantages in improving glycoprotein stability, bioavailability, targeted delivery, and treatment efficacy. In addition to surveying the current landscape, this review delves into the key challenges impeding the widespread adoption of advanced delivery systems, including immunogenicity, manufacturing scalability, and clinical translation. The review concludes with insights into emerging trends in the development of lipid-based delivery systems, positioning glycoprotein therapeutics at the forefront of innovation in biopharmaceuticals. This overview of advancements and challenges aims to provide a roadmap for future progress in the field of glycoprotein delivery and therapeutic applications. Full article

Diabetes mellitus represents a growing global health challenge, establishing oral antidiabetic drugs as a therapeutic class of paramount importance. Consequently, to ensure drug safety, therapeutic efficacy, and accurate therapeutic drug monitoring, robust, selective and highly reproducible analytical methods are indispensable. This review provides a comprehensive overview of instrumental analytical techniques developed between 1985 and 2026 for quantifying oral antidiabetic agents. Based on a literature search across major databases—including PubMed, ScienceDirect and Springer—we systematically evaluated the application of UV-VIS spectrophotometry, liquid chromatography, and advanced electroanalytical methods. The reviewed literature encompasses methodologies ranging from routine quality control of bulk powders and pharmaceutical formulations to complex bioanalytical and pharmacokinetic applications. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) emerged as the gold standard for precise bioanalysis due to its superior selectivity and sensitivity in complex biological matrices. Conversely, UV-VIS spectrophotometry and electrochemical methods remain highly relevant for cost-effective routine quality control in industrial manufacturing. Methodologies are categorized by drug therapeutic class, including biguanides, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, meglitinides, highlighting key validation parameters such as linearity, accuracy, and limits of detection. Finally, this review outlines future directions in the field of antidiabetic drug quantification. Full article

Background: The clinical translation of cell-based therapies for knee articular cartilage repair is fundamentally restricted by the severe biological unpredictability of autologous cell sources, inherent manufacturing bottlenecks, and the rapid phenotypic dedifferentiation of cells expanded in conventional 2D monolayers. To overcome these translational hurdles, this study engineered a scaffold-free, 3D formulation of highly characterized allogeneic FE002-Cart chondroprogenitor spheroids. Methods: We systematically investigated the specific microenvironmental cues and Good Manufacturing Practice (GMP) formulation parameters required to direct functional chondrogenesis. The structural and biochemical performance of this allogeneic formulation was benchmarked against multiple primary adult autologous chondrocyte types. Finally, we evaluated the phenotypic resilience of the microtissues in simulated osteoarthritic (OA) environments and investigated both short-term liquid storage and advanced terminal preservation strategies to establish off-the-shelf logistical viability. Results: Precise microenvironmental regulation proved to be a critical biological prerequisite. The synergistic combination of physiological hypoxia (2% O₂) and stringent glucocorticoid limitation (10 nM dexamethasone) induced robust glycosaminoglycan (GAG) deposition and a > 200-fold upregulation of ACAN and COL2, while suppressing the terminal hypertrophic drift observed in adult chondrocytes. Benchmarking revealed that the allogeneic FE002-Cart formulation substantially mitigates the profound morphological and biochemical unpredictability inherent to adult autologous cell sources. Furthermore, the scaffold-free spheroid geometry yielded a 10-fold increase in GAG production per cell compared to traditional matrix-seeded (MACI) platforms. Transitioning to a GMP-compatible manufacturing process revealed extreme cellular sensitivities; excipients within standard pharmaceutical-grade dexamethasone severely aborted chondrogenic differentiation, emphasizing the necessity of rigorous raw-material qualification. Functionally, the 3D architecture acted as a protective physical shield, sustaining high cellular viability when subjected to severe inflammatory stress and 100% OA patient synovial fluid. Logistically, the viable spheroids maintained matrix integrity and inter-spheroid fusion potential for up to 7 days at ambient temperature in transport medium. Finally, advanced spheroid preservation via lyophilization and high-dose gamma irradiation eliminated biological viability but successfully transitioned the microtissues into highly organized, terminally irradiated matrices capable of heterologous in vitro structural merging. Conclusions: These findings define the critical biological thresholds for manufacturing, demonstrate the enhanced in vitro biosynthetic efficiency of 3D allogeneic microtissues compared to specific autologous and matrix-dependent baselines, and establish a highly practical, off-the-shelf logistical framework for the regenerative treatment of large knee chondral defects. Full article

Background: Poor aqueous solubility of therapeutic molecules remains a limitation in the pharmaceutical development of lipophilic drugs. This requires formulation approaches that provide the desired therapeutic efficacy while being industry-friendly. This study aimed to optimize a thermoresponsive solid dispersion containing atorvastatin calcium to enhance its dissolution performance. Methods: Various nonaqueous solvents were screened to select a thermo-modulating agent. A central composite design was employed to investigate the impact of Pluronic F-68 concentration (5–15% w/w) and atorvastatin calcium concentration (5–10% w/w) on phase transition temperature and phase transition interval. Molecular interactions were assessed by Fourier-transform infrared spectroscopy. The in vitro dissolution of the optimized thermoresponsive solid dispersion was assessed using a USP Apparatus II dissolution test. Results: Propylene glycol was identified as the optimal thermo-modulating agent, forming a rigid carrier through hydrogen bonding with Pluronic F-68. The optimized thermoresponsive solid dispersion consisted of 10.07% w/w Pluronic F-68 and 9.98% w/w atorvastatin calcium. It converted to a solution state at 32 °C. At physiological temperature, the phase transition interval was 111.66 s. Dissolution studies demonstrated that the thermoresponsive solid dispersion enhanced the dissolution profile of atorvastatin calcium within 5 min, 96.6 ± 1.2% compared to 13.8 ± 4.2% for the raw drug. A comparison of process characteristics indicated fewer unit operations and no organic-solvent requirement relative to conventional techniques. Conclusions: This approach enhances dissolution performance and eliminates the need for organic solvents through simple manufacturing processes. Full article

Hydroxypropyl cellulose (HPC) is extensively utilized as a binder and in controlled-release matrices, yet its production predominantly relies on high-purity α-cellulose derived from wood or cotton, which subjects supply chains to sustainability issues and fluctuations in feedstock prices. Annually, sugarcane bagasse, estimated at approximately 490–600 million tons annualy, presents a scalable, residue-based cellulose source for HPC production within circular bioeconomy frameworks. This review compiles findings from 106 peer-reviewed studies on cellulose and HPC derived from bagasse, addressing synthesis methods, structure–property relationships, and pharmaceutical applications. Published studies indicate that HPC derived from bagasse can achieve a degree of substitution (DS 1.87) compared to commonly reported commercial wood-pulp HPC grades (DS 1.8–2.5). Crystallinity reduction relative to commercial HPC has been proposed based on the lower crystallinity of the underlying bagasse cellulose feedstock, but this has not yet been directly measured for the hydroxypropylated product. Beyond performance, bagasse is an agricurtural residue available at negligible feedstock cost, in contrast to the established market prices of purified wood pulp and cotton linter (US$18–25 per kg) used in commercial HPC manufacturing. Life-cycle assessments of bagasse valorization pathways have similarly reported favorable environmental profiles relative to conventional biomass feedstocks. However, no dedicated techno-economic or life-cycle assessment specific to pharmaceutical-grade HPC production from bagasse has been published, and these potential sustainability and cost advantages therefore remain to be formally validated at industrial scale. Key challenges remain in regulatory acceptance, impurity control, batch-to-batch standardization, and scaling up etherification under pharmaceutical good manufacturing practice (GMP) constraints. Overall, the reviewed literature positions sugarcane bagasse (SCB)-derived HPC as a promising candidate for combining excipient performance with potential sustainability and cost benefits, necessitating targeted process optimization and qualification studies to expedite industrial adoption. Full article

Low generic drug prices in the US and Europe have benefited from offshoring production to low-cost overseas plants in countries with a strong manufacturing base, such as China and India. However, the ongoing quality control and reliability issues with the supply chain have engendered discussions on the merits of “reshoring”. This study examines the potential economic impact of reshoring generic drug production by estimating labor compensation cost and productivity in China-based, India-based, and US/EU-based generic firms. We estimate the magnitude of increase in cost of goods sold if drug production is “reshored” from China/India to the US/EU. We construct a sample of ninety generic drug manufacturers headquartered in China (43), India (32), and the US and Europe (15). All selected firms are publicly traded and have at least one production plant inspected by the US Food and Drug Administration between 2017 and 2019. Nearly 90% of generic drug firms in each region are vertically integrated and manufacture both active pharmaceutical ingredients and final drug formulations for generic drugs. The US/EU-based firms face significantly higher labor compensation costs and experience lower operating profit margins compared to China- and India-based firms. A Cobb-Douglas function is constructed to model production for generic drugs in each region. We employ a fixed effect regression model to obtain parameter estimates for the production function and use the estimated total factor productivity to compare the overall productivity across regions. We do not find evidence that US/EU-based generic drug firms have higher productivity. We project variable costs for generic drug production will rise by at least 35–40% if production is reshoring from China or India to the US/EU. Findings from our analyses highlight an urgent need for more in-depth economic analyses to assess the impact of reshoring on costs and ultimately prices for generic drugs in the US/EU market. Full article

Background/Objectives: Andrographolide (AG), the primary diterpene of Andrographis paniculata, is classified as a BCS Class II substance, with its dissolution known to be restricted and inconsistent across various Andrographis extracts and formulations. This study aimed to implement liquisolid (LS) technology to enhance and reduce source-dependent variability in the dissolution of AG from Andrographis paniculata extracts (APEs). Methods: Ethanolic APEs from three distinct sources in Thailand were obtained using Soxhlet extraction. The AG content in the APEs varied between 14.9 and 24.1%. LS powders of APEs and pure AG were fabricated using microcrystalline cellulose and colloidal silicon dioxide as the carriers and coating materials. Their FTIR, PXRD, and SEM characteristics, flowability, and AG content were investigated. Results: All LS formulations exhibited good flowability and assay consistency. FTIR studies suggested intermolecular interactions between the α,β-unsaturated lactone ring of AG and the liquid vehicle. PXRD and SEM studies revealed the non-crystalline state of AG in LS powder, regardless of the AG source. All LS powders, regardless of the AG source, exhibited improved and similar dissolution profiles, with a similarity factor >51 under both sink and non-sink conditions. Preliminary stability assessments demonstrated that all formulated LS powders exhibited no marked physical changes over three months, regardless of the storage conditions. The percentage of AG remaining was significantly affected by storage temperature. Only LS powders stored under refrigerated conditions maintained dissolution patterns similar to those of fresh samples. Conclusions: This study offers foundational insights into LS strategies aimed at improving and reducing the source-dependent variability of herbal-extract powders. Full article

D-lactic acid is a key chiral intermediate widely applied in agriculture, pharmaceuticals, and polylactic acid synthesis, with microbial fermentation as its main production method. Commercial D-lactic acid production depends heavily on refined carbohydrates and yeast extract as carbon and nitrogen sources, resulting in prohibitive raw material costs. Abundant in microbially available proteins and carbohydrates, renewable resources can act as carbon and nitrogen substrates for efficient D-lactic acid production. Repurposing these resources reduces production expenses and is essential for the industrial scaling of D-lactic acid manufacturing. This paper reviews research advances in D-lactic acid fermentation using renewable feedstocks including agricultural wastes, sugar industry residues, oil processing wastes, and cheese processing by-products as carbon and nitrogen sources. Full article

Eye drops remain the principal topical treatment for ocular infections, yet rapid precorneal clearance, variable dose delivery and limited tissue penetration can restrict local drug availability and necessitate frequent administration. Conjunctival inserts have long been investigated as a means of extending ocular residence and thin film inserts offer a more adaptable solid dosage form that may provide a defined drug-containing unit, prolonged local exposure and hydration-dependent dissolution or transformation within the conjunctival sac. Clinical translation remains limited by substantial variability in formulation design, manufacturing control and performance testing. This review critically evaluates the manufacture and characterisation of ocular anti-infective thin film inserts, with the aim of identifying the principal factors that determine reproducibility, interpretability and progression beyond formulation feasibility. Film architecture, polymer selection and drug-loading strategy are considered in relation to the physicochemical characteristics of the active pharmaceutical ingredient and the intended behaviour of the finished insert. Solvent casting remains the most extensively investigated manufacturing approach, while extrusion, electrospinning and additive manufacturing broaden the available processing options. Across these methods, incomplete specification of material and process variables frequently restricts comparison and reproducibility. Testing procedures are similarly heterogeneous and often assess individual attributes without establishing how the finished insert performs under conditions relevant to conjunctival administration. Particular limitations concern dosage-unit uniformity, hydration and matrix transformation, drug-release models and the interpretation of antimicrobial activity. Progression towards clinically relevant products will require indication-led development in which manufacturing control, pharmaceutical quality, ocular compatibility and biorelevant performance evaluation are considered as connected elements. This approach may provide a stronger basis for determining whether the potential advantages of ocular anti-infective thin film inserts can be translated into reproducible and clinically useful dosage forms. Full article

Magnetic polymer nanocomposites (MPNCs) have attracted considerable attention as advanced multifunctional materials for water purification due to their high adsorption capacity, magnetic recoverability, and excellent reusability. This review presents a comprehensive overview of recent developments in the synthesis, characterization, and environmental applications of MPNCs for wastewater treatment. Particular emphasis is placed on the principal synthesis strategies, including in situ and ex situ approaches, and their influence on nanoparticle dispersion, interfacial interactions, and the physicochemical properties of the resulting nanocomposites. The review covers the most widely investigated magnetic nanomaterials, such as Fe₃O₄, γ-Fe₂O₃, CoFe₂O₄, ZnFe₂O₄, and other ferrites, incorporated into natural and synthetic polymer matrices including chitosan, cellulose, alginate, polyaniline, polypyrrole, poly(vinyl alcohol), and polystyrene. Advanced characterization techniques, including X-ray diffraction (XRD), scanning and transmission electron microscopy (SEM/TEM), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), and superconducting quantum interference device (SQUID) measurements, are discussed to evaluate the structural, chemical, thermal, and magnetic properties of these hybrid materials. The adsorption performance and underlying mechanisms of MPNCs for the removal of heavy metals, dyes, pharmaceutical compounds, organic pollutants, and oil contaminants are critically analyzed, highlighting the roles of polymer functionalization, nanocomposite architecture, and magnetic separation in enhancing treatment efficiency and reusability. In addition, the contribution of density functional theory (DFT) to understanding adsorption mechanisms and guiding the rational design of high-performance adsorbents is reviewed. Finally, current challenges and future perspectives, including green synthesis, multifunctional and stimuli-responsive materials, scalable manufacturing, and industrial implementation, are discussed. This review provides a comprehensive framework for the design and development of next-generation magnetic polymer nanocomposites for sustainable water remediation applications. Full article

Organoselenium chemistry has progressed from the early synthesis of simple selenoorganic molecules in the 20th century to advanced methodologies aligned with the principles of green chemistry. Conventional synthetic approaches, frequently dependent on hazardous reagents and organic solvents, are increasingly being replaced by environmentally benign strategies, including solvent-free reactions, aqueous and bio-based solvent systems, microwave-assisted synthesis, and mechanochemical techniques. These sustainable methodologies offer significant advantages, such as enhanced reaction efficiency, higher or comparable yields, reduced waste generation, improved safety, and lower environmental impact. In parallel, evolving regulatory standards and industrial practices are encouraging the adoption of greener synthetic protocols to minimize hazardous waste and support safer pharmaceutical manufacturing. This review systematically categorizes organoselenium compounds, highlighting their synthetic methodologies, structural characteristics, and biological activities. Overall, recent advances emphasize the therapeutic potential of organoselenium compounds and demonstrate the essential role of sustainable synthetic chemistry in the development of future medicinal agents. Full article

Additive manufacturing, also known as 3D printing (3DP), is intended to enable personalised medicine by producing drug products on demand at the Point of Care (PoC), with dose, drug-release profile, and geometry tailored to the individual patient. Despite its promise, widespread adoption is limited by the absence of ready-to-use quality control (QC) methods for printlets at the PoC. Process Analytical Technology (PAT) tools, particularly vibrational spectroscopic methods like Near-Infrared and Raman spectroscopy, can offer real-time monitoring to ensure the safety and consistency of printed dosage forms. Integrating these tools within a Quality-by-Design (QbD) framework can enhance process understanding, control variability, and minimise risk. Regulatory implementation and technological innovation remain essential for the broader clinical implementation of 3DP in pharmaceutical manufacturing. This review presents an overview of currently existing studies on PAT tools explored for non-destructive quality control across 3DP techniques, examines the correlation between Critical Process Parameters (CPPs), Critical Material Attributes (CMAs), and the Critical Quality Attributes (CQAs) of 3D-printed dosage forms within a QbD context, and outlines the current regulatory landscape alongside key limitations and future directions for the broader integration of 3DP into pharmaceutical development and manufacturing. Current evidence shows that PAT application remains uneven across printing technologies and is predominantly directed at final product quality control, rather than the real-time process monitoring required for a fully closed-loop QbD framework. Existing spectroscopic models are largely restricted to single formulations, printers, and APIs, and the absence of standardised validation reporting and transferability assessments represents a key barrier to routine implementation. Full article

Implantable devices have undergone enormous development in the past several decades and more results are expected as there are still unanswered questions. In manufacturing, a relatively new technology called three-dimensional (3D) printing has become increasingly involved, from which hot-melt extrusion (HME) coupled with fused deposition modeling (FDM) is one of the most researched methods in producing implantable drug delivery systems (IDDS). The HME process is used to produce polymer filaments that are the carriers of the applied drugs, while FDM creates the implant itself from the filaments, based on the computer-aided designs. The availability of several polymers like polycaprolactone, polylactic acid, or thermoplastic polyurethane, etc., allows the incorporation of many active pharmaceutical ingredients while digital designs offer numerous variabilities in designs, formulations, and applications of 3D-printed IDDS. This allows more specific and detailed modifications in the end product which can forecast the possibility of personalized treatments and therapies. In this review, our research group gathered together different HME-FDM-printed IDDS to provide examples about the diverse applicability of 3D printing. These products, just like any other device and medicine in the medical field, must be characterized and evaluated properly. The methods and technology that are needed already exist and can be repeatedly used in the characterization of IDDSs; we also discuss these methods based on the available publications. In conclusion, every condition is given to make research and manufacture personalized 3D-printed IDDSs possible, however more research work and proof of safe usage are crucial to make these devices applicable in everyday medical treatments. Full article

Antimicrobial resistance (AMR) in respiratory infections represents a major global health challenge, compounded by biological barriers that limit the effectiveness of conventional antibiotics, including mucus hypersecretion, biofilm formation, and intracellular pathogen persistence. Nanotechnology has emerged as a promising platform for addressing these limitations through advanced drug-delivery strategies. This narrative review provides an integrated overview of nanocarrier systems—including lipid-based (e.g., liposomes, solid lipid nanoparticles), polymeric (e.g., PLGA, chitosan), and inorganic nanoparticles (e.g., silver, gold, zinc oxide)—with emphasis on their pharmaceutical design parameters for pulmonary delivery. Key mechanisms by which nanotechnology enhances antimicrobial efficacy include targeted and controlled drug delivery, improved penetration of mucus and biofilms via surface engineering, synergistic combination therapies, and intrinsic antimicrobial activity through mechanisms such as reactive oxygen species generation. Preclinical studies targeting major respiratory pathogens, including Pseudomonas aeruginosa, Mycobacterium tuberculosis, Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus, demonstrate enhanced biofilm disruption, intracellular drug delivery, and reductions in bacterial burden. However, important translational challenges remain, including long-term safety, manufacturing scalability, regulatory complexity, and the potential for microbial adaptation. Future directions focus on stimuli-responsive systems, inhalable formulations, and biomimetic platforms to improve targeting and therapeutic precision. Collectively, nanotechnology represents a delivery-oriented strategy with the potential to enhance existing antimicrobial therapies and support the development of more effective interventions against resistant respiratory infections. Full article

Background: The development of naturally derived pharmaceutical excipients has attracted increasing interest as alternatives to conventional synthetic materials. Methods: In this study, starch–beeswax composites were prepared using native rice starch (RS) and spray-dried rice starch (SDRS) through melt levigation (ML) and emulsification (EM) techniques at starch-to-beeswax ratios of 9:1, 8:2, and 7:3. The physicochemical properties, surface hydrophobicity, morphology, tabletability, and lubrication performance of the resulting composites were evaluated and compared with magnesium stearate (MGS) and hydrogenated vegetable oil (HVO). Results: Co-processing with beeswax markedly increased the water contact angle from 35.4° and 59.7° for RS and SDRS, respectively, to values ranging from 94.5° to 125.1°, indicating successful modification of surface hydrophobicity. SEM analysis demonstrated changes in particle morphology and surface appearance following co-processing, while FT-IR confirmed the coexistence of characteristic starch- and beeswax-associated spectral features without evidence of detectable covalent modification. Co-processed formulations generally maintained or improved tabletability relative to their corresponding starch bases, with SDRS-based composites producing substantially harder tablets than RS-based formulations. The composites also reduced tablet ejection force and improved tablet mechanical properties compared with lubricant-free formulations. Among all samples, SDRS-EM-73 exhibited the best overall performance, reducing ejection force from 386.5 N for the lubricant-free control to 89.2 N, a value comparable to HVO (93.0 N), while producing tablets with high hardness (60.9 N), low friability (0.16%), and acceptable disintegration time (44.8 s). Conclusions: These findings demonstrate that co-processed starch–beeswax composites, particularly SDRS-EM-73, show considerable potential as naturally derived excipients for tablet manufacturing and may serve as sustainable alternatives to conventional tablet lubricants. Full article