Search Results (122)

Gum arabic (GA) is a widely used natural hydrocolloid in food processing because its protein–polysaccharide architecture combines high water solubility, low bulk viscosity, and useful interfacial activity. These attributes make GA valuable as an emulsifier, encapsulating agent, and film-forming material, but native GA is constrained by source-dependent heterogeneity, limited antioxidant functionality, relatively high dosage requirements in some emulsions, and modest barrier and mechanical performance in dried matrices. This review synthesizes recent advances in chemical functionalization, enzymatic and oxidative grafting, physical fractionation and complexation, and Maillard-type bioconjugation as routes to tailor GA for food engineering applications. Emphasis is placed on process-relevant structure–property relationships, including dynamic adsorption, interfacial rheology, emulsifying and encapsulation efficiency, bulk rheology, powder glass transition and hygroscopicity, film barrier behavior, and release kinetics. Across beverage emulsions, spray-dried powders, coacervates, coatings, and delivery systems, the evidence shows that modification must be selected according to the dominant process bottleneck, such as adsorption kinetics, oxidative stability, drying behavior, or humidity-sensitive matrix mobility. This review also identifies priorities for translation, including model-ready measurements, the management of raw-material variability, scale-up-aware processing, and sustainability and regulatory practicality. Overall, modified GA emerges as a versatile platform for designing more robust, application-specific food colloids, encapsulates, and functional coatings. Full article

This review comprehensively examines the incorporation of nanoparticles (NPs) into biopolymers for 3D printing in biomedical applications, integrating material design, processing strategies, and translational considerations within a unified framework. Different types of NPs are analyzed regarding their effects on mechanical reinforcement, rheological modulation, and structural organization of biopolymeric matrices. The discussion covers principal additive manufacturing technologies, including extrusion-based systems such as fused deposition modeling (FDM) and direct ink writing (DIW), vat photopolymerization, powder-bed fusion (SLS), and emerging in situ nanoparticle formation approaches, emphasizing how nanoparticle loading and surface functionalization govern yield stress, shear-thinning behavior, viscoelastic recovery, and dimensional fidelity while mitigating agglomeration and optimizing interfacial interactions. Comparative evaluation of compressive modulus, strength, toughness, crystallinity, and porosity establishes structure–property–processing relationships directly linked to printability and functional performance. Biomedical applications are addressed in tissue engineering, biosensing, controlled and targeted drug delivery, and bioimaging, highlighting the balance between bioactivity and manufacturability. Finally, critical challenges—including compatibility, reproducibility, biological safety, long-term stability, regulatory adaptation, and environmental impact—are discussed, alongside future perspectives focused on green nanomaterials, AI-driven predictive formulation design, and digital twins for real-time monitoring and quality control in nano-enabled additive manufacturing. Full article

This review summarizes innovative co-formulation strategies for non-marketed dry powder inhalers (DPIs), enabling the simultaneous pulmonary delivery of multiple active pharmaceutical ingredients (APIs). Key approaches include co-amorphous systems (COAMS) and co-crystals, which combine two APIs into a single particle, improving aerodynamic properties, solubility, dissolution, and patient compliance while reducing manufacturing complexity. Core–shell microparticles, produced via spray drying, allow spatial separation and controlled release of APIs, minimizing drug–drug interactions and enabling tailored pharmacokinetics. Co-spray drying of dual APIs can yield particles with superior aerosolization and stability, though examples remain limited. Nanoparticle-based systems offer enhanced lung deposition and cellular uptake but face challenges in device compatibility, scalability, and regulatory approval. Each technology presents unique advantages and limitations regarding manufacturability, dose flexibility, and clinical translation. This review also highlights advances in in vitro toxicity testing, including air–liquid interface cultures, organoids, lung-on-chip models, and precision-cut lung slices, which are increasingly important as alternatives to animal studies. The importance of using an aerosol exposure system for the testing is highlighted. Ultimately, the choice of co-formulation platform should balance scientific innovation with practical considerations of manufacturing and regulatory requirements to maximize therapeutic benefit and commercial viability for future DPI combination products. Full article

Background: Pantoprazole is a widely used proton pump inhibitor that is highly unstable under acidic conditions. This limits the performance of conventional formulations and typically requires enteric-coated dosage forms or alternative modified-release approaches. This study reports the development of polymeric matrix mini-tablets designed to protect pantoprazole during gastric exposure and to enable pH-dependent release under intestinal conditions. The formulations combine Eudragit^® S 100, a pH-dependent polymer, with HPMC, a hydrophilic matrix former that modulates drug release through hydration and swelling. Methods: Matrix mini-tablets were prepared by blending pantoprazole with selected excipients at optimised proportions and compressing the blends by direct compression using an eccentric tablet press. Powder blends and mini-tablets were characterised according to pharmacopoeial specifications. Analytical techniques—including High-Performance Liquid Chromatography (HPLC), Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Absorption Spectroscopy (FT-IR), Powder X-Ray Diffraction (PXRD), and Scanning Electron Microscopy (SEM)—were employed to evaluate drug content uniformity, thermal behaviour, and potential drug–excipient interactions. In vitro dissolution studies were performed under sequential pH conditions, and the release kinetics were analysed using mathematical models. Results: Dissolution testing identified formulations F2 and F6 as providing the most suitable gastro-resistant performance in the acidic stage, together with sustained release up to 24 h. Kinetic modelling supported formulation-dependent release mechanisms, and multivariate analysis (PCA) highlighted relationships between physico-mechanical attributes and drug-release behaviour. Conclusions: The proposed matrix system shows potential as a robust, coating-free platform for the modified delivery of acid-labile drugs using direct compression, simplifying manufacturing. These findings support the rational design of oral modified-release formulations based on polymeric matrices. Full article

Background/Objectives: Clonazepam (CLZ), a BCS Class II drug, presents significant oral delivery challenges due to its low aqueous solubility. This study explores the systematic development of solid self-emulsifying drug delivery systems (S-SEDDS) using Quality by Design (QbD). The primary objective was to evaluate and compare advanced mathematical optimization frameworks, specifically Derringer’s Desirability Function (D) and Weighted Goal Programming (WGP), to identify a robust formulation that enhances drug solubilization while ensuring superior processability and flowability. Methods: Liquid SEDDS were solidified by adsorption onto a porous matrix (Aerosil^® 200/Lactose). A multi-objective optimization was conducted to define a robust Design Space (DS), comparing D against WGP. The trade-offs between competing Critical Quality Attributes (CQAs), specifically powder flowability (angle of repose, AR), blending efficiency (BE), and CLZ recovery (CR), were evaluated. Characterization included morphology from Environmental Scanning Electron Microscopy (ESEM), droplet size analysis, and pH-dependent dissolution studies. Results: D provided a highly robust baseline, yielding constant optimal coordinates (F2, F3 = +1; F4 = 0) across all sensitivity levels, with a predicted AR of 40.46°, BE of 0.12 and CR of 90.0%. However, WGP successfully refined this solution by allowing a more flexible weighting of goals, achieving a more favorable compromise with an AR of 38.96°, a BE of 0.11, and a CR of 90.23%. The optimized system maintained nanometric droplet sizes (<200 nm) and showed a controlled, pH-independent release profile, reaching 80% drug solubilization at 6 h. Conclusions: Integrating WGP into the QbD framework offers a more versatile and precise optimization than the traditional D for complex pharmaceutical systems. This approach ensures the production of high-quality S-SEDDS, bridging the gap between mathematical modeling and the stringent requirements of industrial solid dosage manufacturing. Full article

Background/Objectives: Reproducible evaluation of aerosol dispersibility remains a key challenge in the development of dry powder inhalers (DPIs), where small variations in particle cohesion, morphology, or device resistance can lead to large differences in aerodynamic performance. In passive DPIs, the forces required for powder fluidization and aerosolization arise from the interaction of patient inspiratory airflow with device geometry and must overcome strong interparticle cohesive forces to enable effective lung delivery. Cascade impaction is the gold standard for determining aerodynamic particle size distribution (APSD), but its low throughput and experimental burden limit its utility for systematic formulation and device screening. Prior studies have explored laser diffraction-based particle sizing under varying dispersion energies as indirect metrics of powder dispersibility. Here, we extend this approach by introducing a mathematically rigorous, distribution-based framework that applies the first-order Wasserstein distance (Earth Mover’s Distance) to quantify relative dispersibility with respect to a material-specific maximally dispersed reference state. Methods: Mannitol, trehalose, and inulin were spray-dried under matched conditions to generate model dry powders. Particle size distributions were measured by laser diffraction (Sympatec HELOS/R) using both a RODOS dry dispersion module to define a maximally dispersed reference state and an INHALER module to generate aerosols under clinically relevant dispersion conditions spanning multiple device resistances and pressure drops. For each condition, the Wasserstein-1 distance (W₁) was computed between cumulative volume-based size distributions obtained under reference and inhaler-based dispersion. Cascade impaction was used as an orthogonal method to characterize aerodynamic performance under a representative dispersion condition. Results: W₁ captured formulation-, device-, and flow-dependent differences in dispersibility that were not readily separable by visual inspection of particle size distributions alone. Crystalline mannitol exhibited the largest and most flow-rate-dependent W₁ values, whereas amorphous trehalose and polymeric inulin showed smaller W₁ values with distinct, non-monotonic pressure responses that depended on device resistance. W₁ qualitatively aligned with cascade impaction metrics, exhibiting a positive association with mass median aerodynamic diameter and an inverse association with fine particle fraction, while also demonstrating that efficient dose emission can occur despite incomplete deagglomeration. Conclusions: This study establishes the Wasserstein distance as a physically interpretable, formulation-agnostic metric for quantifying aerosol dispersibility relative to a material-specific reference state. This framework enables systematic comparison of dispersion efficiency across devices and operating conditions using standard laser diffraction data and provides a reproducible basis for mechanistic optimization of DPI formulations and inhaler designs. Full article

Background/Objectives: Carrier-based dry powder inhaler (DPI) formulations remain the predominant platform for respiratory drug delivery. However, integrated development frameworks that align upstream particle engineering with downstream manufacturing are underdeveloped. This study aimed to develop a comprehensive Quality-by-Design (QbD) strategy that systematically connects jet milling, formulation design, and blending scale-up for carrier-based DPI products containing micronized crystalline active pharmaceutical ingredient (API). Methods: Phenytoin was selected as a model API to investigate process–formulation–performance relationships. Jet milling parameters were optimized to generate three distinct API particle size distributions while monitoring solid-state integrity. A design of experiments (DoE) evaluated the impact of API particle size and lactose fines level on aerodynamic performance (fine particle fraction, FPF) and powder processability (flowability, compressibility). High-shear and low-shear blending techniques were compared, and a novel V-shell blending scale-up methodology was developed based on maintaining particle fall velocity and total strain across multiple scales (one-, two-, and eight-quart). Results: Optimized jet milling produced inhalation grade API particles with controlled amorphous content localized to high-energy processes. DoE analysis identified a design space in which API Dv90 of 2.9–4.5 µm and coarse lactose <96% maximized both aerosolization and blend flowability. Low-shear blending achieved superior lung delivery (FPF 62.6 ± 1.7%) compared with high-shear micing (50.1 ± 1.5%). The particle-velocity-based scale up strategy produced statistically equivalent FPF and ED across all scales (p < 0.01), with content uniformity (RSD ≤ 5%) and variability comparable to commercial DPIs. Conclusions: This integrated QbD framework demonstrates that the co-optimization of particle size engineering, formulation composition, and blending dynamics is essential for achieving robust and scalable DPI products. The approach offers a material-sparing, efficient pathway from API characterization through commercial scale manufacturing and is broadly applicable to respiratory drug development. Full article

Folate receptor alpha is expressed at low levels in normal tissues, but is elevated in aggressive breast cancer types and can be utilized for targeted nanoparticle delivery. Hence, we prepared a hybrid nanocarrier based on in-house synthesized mesoporous silica nanoparticles (MSNs) which were further lipid-coated and reinforced with folic acid (FA). Thorough physicochemical evaluation was performed including dynamic light scattering (DLS), powder x-ray diffraction (PXRD), thermogravimetric analysis (TGA), and nitrogen physisorption. In vitro dissolution of the model drug doxorubicin was carried out in release media with pH 7.4 and pH 5.5. The cytotoxic potential and cellular uptake were investigated in MCF-7 breast cancer cells via the MTT assay, doxorubicin fluorescence measurement, and microscopy. The potential amelioration of doxorubicin’s cardiotoxicity was evaluated in vitro on the H9c2 cell line. The results showed MSNs with significant pore volume (1.38 cm³/g) and relatively small sizes (98.05 ± 1.34 nm). The lipid coat and FA attachment improved the physicochemical stability and sustained release pattern over 24 h. MSNs were non-toxic, while when doxorubicin-loaded, they caused moderate cytotoxicity. The highest cytotoxic activity was observed with folate-functionalized, doxorubicin-loaded nanoparticles (NPs). Even though non-loaded folate-functionalized NPs exhibited significant cytotoxicity, their physical mixture with doxorubicin was inferior in MCF-7 cytotoxicity as opposed to the corresponding loaded nanocarrier. Fluorescence-based quantification showed a higher intracellular accumulation of doxorubicin when delivered via NPs. These results demonstrate the potential to use folate-functionalized NPs as carriers for doxorubicin delivery in breast cancer cells. Its cardiotoxicity was significantly reduced in the case of loading onto the folic acid-functionalized lipid-coated MSNs. All these findings provide a promising proof-of-concept, although further experimental validation, particularly regarding targeting selectivity and safety, is required. Full article

Tuberculosis (TB) remains a leading infectious killer, increasingly complicated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) disease; current regimens, although effective, are prolonged, toxic, and often fail to reach intracellular bacilli in heterogeneous lung lesions. This narrative review synthesizes how next-generation antimycobacterial strategies can be translated “from molecule to patient” by coupling potent therapeutics with delivery platforms tailored to the lesion microenvironment. We survey emerging small-molecule classes, including decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) inhibitors, mycobacterial membrane protein large 3 (MmpL3) inhibitors, and respiratory chain blockers, alongside optimized uses of established agents and host-directed therapies (HDTs). These are mapped to inhalable and nanocarrier systems that improve intralesional exposure, macrophage uptake, and targeted release while reducing systemic toxicity. Particular emphasis is placed on pulmonary dry powder inhalers (DPIs) and aerosols for direct lung targeting, stimuli-responsive carriers that trigger release through pH, redox, or enzymatic cues, and long-acting depots or implants that shift daily dosing to monthly or quarterly schedules to enhance adherence, safety, and access. We also outline translational enablers, including model-informed pharmacokinetic/pharmacodynamic (PK/PD) integration, device formulation co-design, manufacturability, regulatory quality frameworks, and patient-centered implementation. Overall, aligning stronger drugs with smart delivery platforms offers a practical pathway to shorter, safer, and more easily completed TB therapy, improving both individual outcomes and public health impact. Full article

The breakup process of molten metal is the most critical stage in atomization powder production. Conducting systematic research on the breakup process of molten metal during gas atomization is highly significant for understanding the formation mechanism of droplets. In this study, a mathematical model suitable for investigating the breakup mechanism of molten aluminum in high-speed gas atomization was developed by coupling large eddy simulation (LES) with the volume of fluid (VOF) model, incorporating adaptive mesh refinement technology and periodic boundary conditions. Furthermore, the breakup behavior of molten aluminum in two close-coupled atomizers with distinct delivery tube end geometric (non-expanded type and expanded type, abbreviated as ET atomizer and NET atomizer) were compared. The development of surface waves, as well as the formation mechanisms of liquid cores, liquid ligaments, and liquid droplets during gas atomization, were systematically analyzed. The results indicated that Kelvin–Helmholtz instability was the predominant factor contributing to the primary breakup of molten metals. For the NET atomizer, the recirculation zone predominantly governed the primary breakup of molten metal, whereas the nitrogen main jet primarily controlled the secondary breakup. In the case of ET atomizer, under the influence of atomizing gas, a “conical” liquid core gradually formed, and numerous primary liquid droplets separated from the liquid core before undergoing secondary breakup. Compared to the ET atomizer, the NET atomizer produced droplets with a smaller average size. Full article

Background/Objectives: Hydroxyapatite (HAp)-based implants and HAp–titanium (HApTi) composites are widely used in orthopedic and dental applications, but their long-term success is limited by peri-implant bone loss. Local delivery of osteoactive molecules from implant surfaces may enhance osseointegration and reduce periprosthetic osteolysis. This study combined in silico modeling and experimental assays to compare calcium fructoborate (CaFb), sodium alendronate, and calcium alendronate as functionalization agents for HAp and HApTi implants. Methods: Molecular docking (AutoDock 4.2.6) and 100 ns molecular dynamics (MD) simulations (AMBER14 force field, SPC water model) were performed to characterize ligand–substrate interactions and to calculate binding free energies (ΔG_binding) and root mean square deviation (RMSD) values for ligand–HAp/HApTi complexes. HAp and HApTi discs obtained by powder metallurgy were subsequently functionalized by surface adsorption with CaFb or alendronate salts. The amount of adsorbed ligand was determined gravimetrically, and in vitro release profiles were quantified by HPTLC–MS for CaFb and by HPLC after FMOC derivatization for alendronates. Results: CaFb–HAp and CaFb–HApTi complexes showed the lowest binding free energies (−1.31 and −1.63 kcal/mol, respectively), indicating spontaneous and stable interactions. For HAp-based complexes, the mean ligand RMSD values over 100 ns were 0.27 ± 0.17 nm for sodium alendronate, 0.72 ± 0.28 nm for calcium alendronate (range 0.35–1.10 nm), and 0.21 ± 0.19 nm for CaFb (range 0.15–0.40 nm). For HApTi-based complexes, the corresponding RMSD values were 0.30 ± 0.15 nm for sodium alendronate, 0.72 ± 0.38 nm for calcium alendronate and 0.26 ± 0.14 nm for CaFb. These distributions indicate that CaFb and sodium alendronate maintain relatively stable binding poses, whereas calcium alendronate shows larger conformational fluctuations, consistent with its less favorable binding energies. Experimentally, CaFb exhibited the greatest chemisorbed amount and percentage on both HAp and HApTi, followed by sodium and calcium alendronate. HApTi supported higher loadings than HAp for all ligands. Release studies demonstrated a pronounced burst and rapid plateau for both alendronate salts, whereas CaFb displayed a slower initial release followed by a prolonged, quasi-linear liberation over 14 days. Conclusions: The convergence between in silico and adsorption–release data highlights CaFb as the most promising candidate among the tested ligands for long-term functionalization of HAp and HApTi surfaces. Its stronger and more stable binding, higher loading capacity and more sustained release profile suggest that CaFb-coated HApTi implants may provide a favorable basis for future in vitro and in vivo studies aimed at improving osseointegration and mitigating periprosthetic osteolysis, although direct evidence for osteolysis prevention was not obtained in the present work. Full article

Background/Objectives: This study aims to investigate the underexplored impact of capsule type on the performances of capsule-based dry powder inhalers (cDPIs). It compares specific properties of hard gelatin-based capsules (Hard Gelatin Capsules (HGC), HGC including polyethylene glycol (HGC + PEG)) and hypromellose-based capsules, (Zephyr^® Vcaps^® (VC), Zephyr^® Vcaps^® Plus (VCP) and Vcaps^® Plus Zephyr Inhance™ (VCP-I)) with aerosolization performances of model carrier-based formulation, providing insights into their impact on pulmonary drug delivery efficacy. Methods: Aerosolization properties of a model phenytoin/lactose blend formulation filled in the different capsules was evaluated using a Next Generation Impactor (NGI) with RS01 device. Capsule shell characteristics were evaluated in terms of water activity, static charges, and inner surface aspect and roughness. Results: Hypromellose-based capsules, especially VC and VCP-I, exhibited significantly higher drug delivery performances compared to gelatin-based capsules. In particular, VCP-I demonstrated good results with excellent batch-to-batch reproducibility and 51% of the nominal dose available for lung absorption. Although capsule inner surface showed clear differences between both polymer families, no clear correlation could be found between cDPI performances and capsule roughness and density of charge. All capsules presented good mechanical properties in the conditions of the tests. Conclusions: Capsule type exerts a significant impact on cDPI performances. These findings highlight the importance of capsule selection as a critical material attribute in the design and optimization of inhalation products. Full article

The actual problem in manufacturing functionally graded materials (FGMs) produced in the laser powder bed fusion (LPBF) process remains the controllability of the materials gradient and the properties gradient of the final product. The key element in gradient formation is the delivery system in conjunction with the properties of the powder materials. This paper presents the first preliminary stage of the study, an application of a model based on the discrete element method to simulate several powder delivery systems and the analysis of the results obtained. Two designs of LPBF machine constructions with one and two movable platforms are simulated with and without separation walls. The variants of initial powder material separation were modeled along the longitudinal axis, inclined, and periodic lines. The powder material of the same or different densities and particle sizes was analyzed. The mean diameters of the powder particles in simulations are 0.78 and 0.6 mm, and the ratio of the material densities is 1.0 or 1.5. The 15 multi-stage delivery processes were simulated. The influence of various constructive and material parameters on the segregation (percolation) process and final distribution of powder materials was analyzed. It is shown that constructive elements can be more significant than initial material distribution in controlling the final distribution; limiting percolation in the transverse direction remains a major challenge for the distribution system in gradient control. The results demonstrate the usefulness and suitability of applying simulations with the developed model to the design of the powder delivery system and define a direction for further theoretical and experimental research. Full article

Optical fiber radiation sensing probes made using inorganic scintillator materials have notable advantages in achieving high spatial resolution and building sensing arrays due to their small size and excellent linearity, serving as a key tool for dose measurement in precision radiotherapy. This study establishes a theoretical model for scintillator luminescence coupling into optical fibers, and derives a fluorescence intensity calculation formula based on the fiber’s numerical aperture and fluorescence self-absorption. The light intensity response to scintillator length for different absorption coefficients is established based on numerical simulation, providing a nonlinear fitting equation, resulting in a novel “effective length of scintillator” concept. Five probes with scintillator lengths of 0.2 mm, 0.5 mm, 1.0 mm, 1.5 mm, and 2.0 mm were prepared in the laboratory using a 3:1 mass ratio mixture of UV-setting epoxy and Gd₂O₂S:Tb powder. Tests in a clinical radiation delivery setting showed good agreement between experimental data and theory, confirming optimum effective length of the scintillator as 0.62 mm. This study indicates that inorganic scintillators for end-constructed probes do need not need to be excessively long. Analyzing the effective length can reduce scintillator usage, simplify fabrication and processing, and enhance the probe’s spatial resolution without decreasing the signal-to-noise ratio, thus offering new insights for optimizing optical fiber radiation probes. Full article

Background/Objectives: Prodrug strategies are a vital aspect of drug development, with ester prodrugs particularly notable for modifying parent drug properties through ester functional groups to enhance oral absorption. However, ester prodrugs are prone to hydrolysis by water and enzymes, making stability in the gastrointestinal (GI) tract prior to absorption a key challenge. Few formulation strategies effectively address this degradation issue. We recently introduced binary lipid systems (BLS), comprising a lipid and a water-soluble surfactant only that form stable microemulsions. This study aimed to explore the application of BLS for enhancing the oral absorption of ester prodrugs by coating drug crystals with BLS in solid granules and study the impact of the compositions of BLS on oral absorption. Methods: Olmesartan medoxomil (OLM), a methyl ester prodrug of olmesartan (OL), was selected as a model drug. Various lipids were combined with TPGS to form BLS and used to prepare OLM solid granules containing OLM crystals. Results: Among the tested formulations, OLM MCM-TPGS granules significantly enhanced drug release and protected OLM from enzyme-mediated degradation in two-step dissolution studies with esterase. Pharmacokinetic and tissue distribution studies in rats confirmed that OLM MCM-TPGS granules improved oral absorption by 145% and increased tissue uptake compared to OLM powder. Conclusions: This approach overcomes solubility limitations when using lipids and surfactants as excipients, enabling high drug loading in solid dosage forms and expanding the utility of lipids and surfactants for water-insoluble drugs. This novel formulation strategy holds great potential for enhancing oral absorption of ester prodrugs, representing a significant advancement in formulation technologies and offering more effective and versatile drug delivery solutions. Full article