Search Results (92)

X-ray absorption spectroscopy (XAS) and X-ray emission spectroscopy (XES) are analytical techniques enabling precise analysis of the electronic structure and local atomic environment in chemical compounds and materials. Their application spans materials science, chemistry, biology, and environmental sciences, supporting studies on catalytic mechanisms, redox processes, and metal speciation. A key advantage of both techniques is element selectivity, allowing the analysis of specific elements without matrix interference. Their high sensitivity to chemical state and coordination enables determination of oxidation states, electronic configuration, and local geometry. These methods are applicable to solids, liquids, and gases without special sample preparation. Modern XAS and XES studies are typically performed using synchrotron radiation, which provides an intense, monochromatic X-ray source and allows advanced in situ and operando experiments. Sub-techniques such as XANES (X-ray absorption near-edge structure), EXAFS (Extended X-ray Absorption Fine Structure), and RIXS (resonant inelastic X-ray scattering) offer enhanced insights into oxidation states, local structure, and electronic excitations. Despite their broad scientific use, applications in pharmaceutical research remain limited. Nevertheless, recent studies highlight their potential in analyzing crystalline active pharmaceutical ingredients (APIs), drug–biomolecule interactions, and differences in drug activity. This review introduces the fundamental aspects of XAS and XES, with an emphasis on practical considerations for pharmaceutical applications, including experimental design and basic spectral interpretation. Full article

Pharmaceutical formulations, in addition to the medicinal substance(s), contain added excipients that make it possible to create a pharmaceutical product that exhibits required properties in terms of mechanical, physical, chemical, and microbiological stability. Additionally, these substances can act as release modifiers or improve bioavailability parameters. Literature data indicate that excipients, especially polymeric ones, can also affect the polymorphism of the active substance, resulting in drug bioavailability enhancement or reduction. This influence can be evaluated using thermal and spectroscopic methods. In the study, differential scanning calorimetry (DSC), vibrational spectroscopic studies (Fourier transform infrared spectroscopy, FTIR), Raman spectroscopy, and X-ray diffraction (XRD) assay of ibuprofen, naproxen, and naproxen sodium standards and pharmaceutical preparations containing these medicinal substances in their compositions were carried out. DSC results indicated that a sharp melting peak was observed on the DSC curves of the standards, confirming their crystalline form. DSC results obtained for pharmaceutical formulations also indicated that the enthalpy of melting is sometimes lower than calculated from the percentage of active ingredients in the formulations. In addition, the melting peak is often broadened and shifted toward lower temperatures, suggesting the influence of excipients on the polymorphism of drug substances. The FTIR and Raman spectra of pharmaceutical formulations contained all characteristics of the active substances. XRD analysis was also performed. Therefore, possible chemical interactions between the components of the preparations have been excluded. At the same time, FTIR and Raman spectroscopy results as well as XRD assay showed a reduction in the height of signals corresponding to the crystalline API form, confirming the possibility of reducing API crystallinity in pharmaceutical formulations. Full article

Protective coatings are essential for extending the service life of components exposed to harsh conditions, such as pipes used in industrial systems, where wear and corrosion remain constant challenges. This study explores the development of a nano-sized TiO₂-reinforced electroless nickel-based ternary (Ni-W-P) alloy and composite coating on API X60 steel, a high-strength carbon steel pipe grade widely used in oil and gas pipelines, using an alkaline hypophosphite-reduced bath. The surface morphology, microstructure, elemental composition, structure, phase evolution, adhesion, and roughness of the coatings were analyzed using optical microscopy, FESEM, EDS, XRD, AFM, cross-cut tape test, and 3D profilometry. The tribological performance was evaluated via Vickers microhardness measurements and reciprocating wear tests conducted under dry conditions at a 5 N load. The TiO₂ nanoparticle-reinforced composite coating achieved a consistent thickness of approximately 24 µm and exhibited enhanced microhardness and reduced coefficient of friction (COF), although the addition of nanoparticles increased surface roughness (S_a). Annealing the electroless composites at 400 °C led to a significant improvement in their tribological properties, primarily owing to the grain growth, phase transformation, and Ni₃P crystallization. XRD analysis revealed phase evolution from an amorphous state to crystalline Ni₃P upon annealing. Both the alloy and composite coatings exhibited excellent adhesion performances. The combined effect of TiO₂ nanoparticles, tungsten, and Ni₃P crystallization greatly improved the wear resistance, with abrasive and adhesive wear identified as the dominant mechanisms, making these coatings well suited for high-wear applications. Full article

Poor aqueous solubility still disqualifies many promising drug candidates at late stages of development. Amorphous solid dispersion (ASD) technology solves this limitation by trapping the active pharmaceutical ingredient (API) in a high-energy, non-crystalline form, yet most marketed ASDs rely on synthetic carriers such as polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC), which raise concerns about long-term biocompatibility, residual solvent load, and sustainability. This study summarizes the emergence of natural polymer-based ASDs (NP-ASDs), along with the bond mechanism reactions through which these natural polymers enhance drug performance. As a result, NP-ASDs exhibit improved physical stability and significantly enhance the dissolution rate of poorly soluble drugs. The structural features of natural polymers play a critical role in stabilizing the amorphous state and modulating drug release profiles. These findings support the growing potential of NP-ASDs as sustainable and biocompatible alternatives to synthetic carriers in pharmaceutical development. Full article

Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus^® and Kollidon^® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption. Full article

Background/Objectives: This study investigates the impact of high humidity (25 °C, 75% relative humidity) on gelatin and hydroxypropyl methylcellulose (HPMC) capsules used in dry powder inhalers (DPIs), focusing on moisture dynamics, structural responses, and mechanical performance, with an emphasis on understanding how different capsule types respond to prolonged exposure to humid conditions. Methods: Capsules were exposed to controlled humidity conditions, and moisture uptake was measured via thermal analysis. Visual observations of silica bead color changes were performed to assess moisture absorption, while surface wettability was measured using the sessile drop method. Hardness testing, mechanical deformation, and puncture tests were performed to evaluate structural and mechanical changes. Positron annihilation lifetime spectroscopy (PALS) was used to analyze free volume expansion. Results: HPMC capsules exhibited rapid moisture uptake, attributed to their lower equilibrium moisture content and ability to rearrange dynamically, preventing brittleness. In contrast, gelatin capsules showed slower moisture absorption but reached higher equilibrium levels, resulting in plasticization and softening. Mechanical testing showed that HPMC capsules retained structural integrity with minimal deformation, while gelatin capsules became softer and exhibited reduced puncture resistance. Structural analysis revealed greater free volume expansion in HPMC capsules, consistent with their amorphous nature, compared with gelatin’s semi-crystalline matrix. Conclusions: HPMC capsules demonstrated superior humidity resilience, making them more suitable for protecting moisture-sensitive active pharmaceutical ingredients (APIs) in DPI formulations. These findings underline the importance of appropriate storage conditions, as outlined in the Summary of Product Characteristics, to ensure optimal capsule performance throughout patient use. Full article

Background: The solubility and phase behavior of APIs are crucial for the development of medicines and ensuring their stability. However, conventional experimental approaches often do not allow for the precise determination of phase transitions and solubility limits, especially for poorly soluble compounds. Purpose: The aim of this study was to demonstrate the possibility of using the laser microinterferometry method, traditionally used to define the phase equilibria of polymer systems, to determine the thermodynamic solubility of the APIs. Methods: Using laser microinterferometry, the thermodynamic solubility and phase behavior of amorphous darunavir were determined in various pharmaceutical solvents, including vaseline and olive oils, water, glycerol, alcohols (methanol, ethanol, isopropanol), glycols (propylene glycol, polyethylene glycol 400, polypropylene glycol 425, polyethylene glycol 4000), and ethoxylated polyethylene glycol ether obtained from castor oil in the temperature range of 25–130 °C. Dissolution kinetics was estimated at 25 °C. Hansen solubility parameter calculations were also performed for comparison. Results: Darunavir is practically insoluble in olive and vaseline oils. In water and glycerol, an amorphous equilibrium with an upper critical solution temperature was observed, and phase diagrams were constructed for the first time. In alcohols, glycols, and ethoxylated polyethylene glycol ether obtained from castor oil, darunavir showed high solubility, accompanied by the formation of crystalline solvates. Kinetic evaluation showed that the dissolution rate of darunavir in methanol is four times faster than in ethanol and thirty times faster than in isopropanol. Comparison of the obtained data with previously published and calculated values of solubility parameters demonstrates a good correlation. Conclusions: Laser microinterferometry has been demonstrated as a potential tool for determining the thermodynamic solubility of APIs. This method allows for directly observing the dissolution process, determining the solubility limits, and detecting phase transitions. These studies are necessary for selecting appropriate excipients, preventing the formation of undesirable solvates and predicting formulation stability, which are all critical factors in early-stage drug development and pharmaceutical formulation design. Full article

Background/Objectives: Increasing the solid-state landscape of an active pharmaceutical ingredient (API) by generating new crystalline forms (e.g., polymorphs, cyclodextrin (CD) inclusion complexes, co-crystals, and salts) can yield products with significantly enhanced biopharmaceutical properties (especially increased water solubility), thereby improving API delivery and extending its lifetime. The aim of this study was the isolation of new solid forms of the poorly water-soluble non-steroidal anti-inflammatory drug fenbufen (FBF), for which relatively few solid phases have been reported to date. Further motivation for the study is the recent finding that it has potential for repurposing to treat acute pancreatitis. Methods: Interventions for generating new solid forms of FBF included (a) polymorph screening with a variety of solvent media, (b) attempts to form solid inclusion complexes with the native cyclodextrins α-, β-, and γ-CD using various preparative methods, and (c) co-crystallization with a series of coformers to produce co-crystals and/or molecular salts. Results: No new polymorphic forms of FBF were identified, but screening with CDs resulted in isolation and characterization of a new solid inclusion complex with γ-CD. However, co-crystallization of FBF with the water-soluble coformer isonicotinamide yielded two new products, namely a 1:1 co-crystal and an unusual multi-component ionic co-crystal, whose aqueous solubility indicated significant enhancement of FBF solubility. Conclusions: Due to its extremely low water solubility, FBF presented challenges during the study aimed at modifying its crystalline form. However, two new supramolecular forms, a co-crystal and an ionic co-crystal, were isolated, the latter phase having potential for further formulation owing to its significantly enhanced solubility. Full article

Due to advances in edible films based on polysaccharides that can carry an active pharmaceutical ingredient (API), these films now provide rapid and effective release upon consumption. These films provide an alternative to conventional drug delivery methods and are known as orally disintegrating films (ODFs). This study aimed to evaluate the capacity of an edible film composed of starch, chitosan, and maltodextrin to carry an API while maintaining its physicochemical and surface properties. Acetaminophen, a hydrophilic drug, was selected as the model API and incorporated into the edible film. The film achieved an API loading capacity of approximately 4.37 mg—comparable to the standard doses of certain hydrophilic drugs. Chemical analysis using vibrational spectroscopy revealed strong intermolecular interactions between the components. X-ray diffraction analysis confirmed these interactions through a decrease in crystallinity within the biopolymeric compounds, while the model API retained its structural ordering. However, water absorption values increased by approximately 90% in the edible film. Scanning electron microscopy images showed a homogeneous dispersion of the model API throughout the film, without aggregation, demonstrating that the film can effectively accommodate this drug concentration. Furthermore, the elasticity remained comparable in both formulations, with a Young’s modulus of 9.27 MPa for the control film and 9.38 MPa for the API-loaded film. Overall, the edible film developed in this study represents a promising system for API delivery. Full article

The objective of this work was to investigate the use of nanocrystalline cellulose (NCC) as a drug-delivery excipient for buccal films. Gel-like dispersions were created by blending either gel or powder NCC (gNCC or pNCC) with natural polymers (alginate, pectin, or chitosan) in water, with glycerol serving as a plasticiser. Ibuprofen (IBU) as an active pharmaceutical ingredient (API) was dissolved in a self-microemulsifying drug delivery system (SMEDDS) to improve its solubility prior to its addition to gel-like dispersions. Dispersions were dried, and resulting films were cut to 3 cm × 1.5 cm size, appropriate for buccal delivery. Rheological measurements revealed that shorter, thinner, and less crystalline nanocellulose fibres are more favourable for stronger gel properties. While overall, weaker gel structure prior to film casting also resulted in shorter disintegration time, this was not the case for NCC–chitosan films; here, the low solubility of chitosan in neutral media proved to be the main obstacle. Nevertheless, the prolonged disintegration of NCC–chitosan films did not impact the dissolution of IBU, as these films exhibited the fastest dissolution rate, followed by NCC–pectin and NCC–alginate. Furthermore, NCC properties significantly influenced the dissolution behaviour of the chitosan formulations, with gNCC favouring faster IBU release due to weaker gel formation prior to film casting. Full article

Background/Objectives: This study investigates the preparation of coamorphous systems composed entirely of active pharmaceutical ingredients (APIs), namely praziquantel, niclosamide, and mebendazole. The objective was to formulate and characterize binary and ternary coamorphous systems to evaluate their structural, thermal, and stability properties. Methods: Ten different mixtures (binary and ternary) were designed through a mixture design approach and prepared using a sustainable, one-step neat grinding process in a lab-scale vibrational mill. The systems were prepared reproducibly within 4 h across the entire experimental domain. Structural characterization was performed using PXRD and FTIR to confirm the absence of crystalline domains and the presence of molecular interactions. The glass transition temperature (T_g) was theoretically calculated using the Gordon–Taylor equation for three-component systems and determined experimentally via DSC. Stability studies were conducted on seven systems under different storage conditions (−30 °C, 5 °C, 25 °C, and 40 °C) for six months. Results: PXRD analysis confirmed the formation of coamorphous systems with no crystalline phases. DSC revealed a single T_g for most systems, indicating homogeneity. Stability studies demonstrated that five out of seven systems adhered to the “T_g—50 °C” stability rule, remaining physically stable over six months. Recrystallization studies indicated diverse pathways: some systems reverted to their original crystalline phases, while others formed new entities such as cocrystals. Conclusions: This study highlights the feasibility of coamorphous systems composed of multiple APIs using a simple, solvent-free grinding approach. The findings underscore the importance of molecular interactions in determining stability and recrystallization behavior, offering insights for designing robust coamorphous formulations. Full article

Amorphous solid dispersion (ASD) technology is often used as a promising strategy to improve the solubility of active pharmaceutical ingredients (APIs). ASDs allow APIs to be dispersed at the molecular level in a polymer carrier, destroying the crystalline structure of the APIs and, thanks to the polymer, providing long-term supersaturation in solution. However, stability issues are an obstacle to the development of new medications with ASD. In addition to the molecular mobility at elevated temperatures leading to the crystallization of APIs, moisture affects the physical stability of ASD, leading to fractional separation and recrystallization. N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3) is an original API with both anxiolytic and antidepressant activity, but its insolubility in water can negatively affect (influence) bioavailability. Our study aims to create ASD GML-3 with moisture-resistant polymers (Soluplus^®, HPC) and assess the stability of the amorphous state of ASD after storage in high humidity conditions. As a result, HPC Klucel^TM FX was revealed to be more stable than the brand, providing a high level of API release into the purified water environment and stability after 21 days (3 weeks) of storage in high humidity conditions. Full article

Phase separation is quite common in formulations for hydrophobic active pharmaceutical ingredients (APIs) due to their thermodynamic instability in a supersaturated state during in vitro dissolution or in vivo absorption. Phase separation possibly accompanies the formation of a disordered drug-rich phase, but this is still not thoroughly understood. In this study, the phase separation of supersaturated axitinib (Axi) in media with or without polymers was evaluated via multiple analytical methods, including UV–vis and fluorescence spectroscopy, dynamic light scattering, and microscopy. The phase separation of Axi occurred at an Axi concentration of 25–30 µg/mL in the media, while the addition of quantitative hypromellose acetate succinate (HPMCAS) MG and povidone (PVP) K30 did not alter its phase separation concentration. The second scattering dispersion phase of the system exhibited superior stability and reversibility as the formative filamentous crystalline condensates could disintegrate upon dilution. These disparate analyses consistently detected the phase separation of Axi. This manuscript could provide a better understanding of the supersaturation state of hydrophobic APIs upon pharmaceutical application. Full article

Background: Melt-based 3D printing technologies are currently extensively evaluated for research purposes as well as for industrial applications. Classical approaches often require intermediates, which can pose a risk to stability and add additional complexity to the process. The Advanced Melt Drop Deposition (AMDD) technology, is a 3D printing process that combines the principles of melt extrusion with pressure-driven ejection, similar to injection molding. This method offers several advantages over traditional melt-based 3D printing techniques, making it particularly suitable for pharmaceutical applications. Objectives: This study evaluates the AMDD printing system for producing solid oral dosage forms, with a primary focus on the thermo-stable polymer polyvinyl alcohol (PVA). The suitability of AMDD technology for creating amorphous solid dispersions (ASDs) is also examined. Finally, the study aims to define the material requirements and limitations of the raw materials used in the process. Methods: The active pharmaceutical ingredients (APIs) indometacin and ketoconazole were used, with PVA 4-88 serving as the carrier polymer. Powders, wet granulates, and pellets were investigated as raw materials and characterized. Dissolution testing and content analyses were performed on the printed dosage forms. Solid-state characterization was conducted using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Degradation due to thermal and mechanical stress was analyzed using nuclear magnetic resonance spectroscopy (NMR). Results/Conclusions: The results demonstrate that the AMDD 3D printing process is well-suited for producing solid dosage forms. Tablets were successfully printed, meeting mass uniformity standards. Adjusting the infill volume from 30% to 100% effectively controlled the drug release rate of the tablets. Solid-state analysis revealed that the AMDD process can produce amorphous solid dispersions with enhanced solubility compared to their crystalline form. The experiments also demonstrated that powders with a particle size of approximately 200 µm can be directly processed using AMDD technology. Full article

This technical paper delves into the creation and application of an enhanced mathematical model for semi crystalline thermoplastics based on the Pressure-Volume-Temperature (PVT) Two Domain Tait Equation. The model is designed to incorporate the impact of the cooling rate on the specific volume of the material. This is achieved by utilizing Flash differential scanning calorimetry (fDSC) measurements, thereby ensuring a direct correlation to the actual behavior of the material in reality. The practical application of the model in the context of injection molding simulation was also considered. This was done by integrating the mathematical model into the Moldflow software via the Solver API. The paper underscores the discontinuity issue inherent in the traditional Tait equation with cooling rates and proposes a solution that guarantees a correct transition from the liquid to the solid phase, even at high cooling rates and pressures. The results demonstrated a realistic PVT curve across a wide range of cooling rates and high pressures. The model was put to the test using a 3D tetrahedron meshed calculation model in the injection molding simulation. This study marks a significant step forward in the simulation of injection molding processes, as it successfully bridges the gap between real material properties and simplified simulation, paving the way for more accurate and efficient simulations in the future. Full article