Search Results (407)

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

Although Zn (II)-(−)-Epigallocatechin gallate (EGCg) complex (Zn-EGCg) is known for its promising bioactivities, little attention has been paid to its incorporation into daily green tea consumption. In this study, we aimed to incorporate Zn (II) into green tea extract to promote the formation of Zn-EGCg complex within the tea matrix. We then investigated how the formation of Zn-complexed green tea extract (Zn-GTE) influences the gut microbiota in a Western diet (WD)-fed mouse model. Structural analyses using ultraviolet–visible spectroscopy (UV–Vis), Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR), and powder X-ray diffraction (PXRD) suggested that Zn (II) interacted with hydroxyl groups of polyphenols within the extract, consistent with Zn-EGCg formation, although the complex could not be unequivocally identified. Under intake levels equivalent to daily consumption, Zn-GTE administration restored WD-induced reductions in alpha-diversity and resulted in a distinct microbial composition compared to treatment with green tea extract (GTE) or Zn alone, as shown by beta-diversity analysis. Linear discriminant analysis Effect Size (LEfSe) analysis revealed increased abundances of bacterial taxa belonging to o_Clostridiales, o_Bacteroidales, and f_Rikenellaceae, and decreased abundances of g_Akkermansia in the Zn-GTE group compared to the GTE group. These findings highlight that Zn-GTE, prepared via Zn (II) supplementation to green tea, may exert distinct microbiota-modulating effects compared to its individual components. This study provides new insights into the role of dietary metal–polyphenol complexes, offering a food-based platform for studying metal–polyphenol interactions under physiologically relevant conditions. Full article

In this study, high-energy milled (HEM) samples of natural phosphorites from Estonian deposits were investigated. The activation was performed via planetary mill with Cr-Ni grinders with a diameter of 20 mm. This method is an ecological alternative, since it eliminates the disadvantages of conventional acid methods, namely the release of gaseous and solid technogenic products. The aim of the study is to determine the changes in the structure to follow the solid-state transitions and the isomorphic substitutions in the anionic sub-lattice in the structure of the main mineral apatite in the samples from Estonia, under the influence of HEM activation. It is also interesting to investigate the influence of HEM on structural-phase transformations on the structure of impurity minerals-free calcite/dolomite, pyrite, quartz, as well as to assess their influence on the thermal behavior of the main mineral apatite. The effect of HEM is monitored by using a complex of analytical methods, such as chemical analysis, powder X-ray diffraction (PXRD), wavelength-dispersive X-ray fluorescence (WD-XRF) analysis, and Fourier-transformed infrared (FTIR) analysis. The obtained results prove the correlation in the behavior of the studied samples with regard to their quartz content and bonded or non-bonded carbonate ions. After HEM activation of the raw samples, the following is established: (i) anionic isomorphism with formation of A and A-B type carbonate-apatites and hydroxyl-fluorapatite; (ii) solid-phase synthesis of calcium orthophosphate-CaHPO₄ (monetite) and dicalcium diphosphate-β-Ca₂P₂O₇; (iii) enhanced chemical reactivity by approximately three times by increasing the solubility via HEM activation. The dry milling method used is a suitable approach for solving technological projects to improve the composition and structure of soils, increasing soil fertility by introducing soluble forms of calcium phosphates. It provides a variety of application purposes depending on the composition, impurities, and processing as a soil improver, natural mineral fertilizer, or activator. Full article

Stability assessments of drug substances and the detection of crystalline forms are critical for ensuring drug quality and medication safety. Atorvastatin calcium drug substance samples were characterized using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). DSC results demonstrated a precise discrimination of the stability of samples. An analysis of PXRD characteristic peaks and DSC melting data suggested that instability likely stems from the presence of the amorphous phase. To validate this hypothesis, blended samples containing controlled ratios of amorphous phase and crystalline Form I were prepared. Quantitative models based on PXRD, DSC, and near-infrared spectroscopy (NIRS) data were developed to predict amorphous content, and classification accuracy was evaluated. Experimental results confirmed that all three models achieved classification accuracy values exceeding 70% in the stability prediction of the two groups of samples, which included “stable” and “unstable” samples, substantiating the hypothesis. Among them, the modeling method based on NIRS data was not only non-destructive and rapid but also demonstrates a superior discrimination accuracy value reaching 100% (n = 11), showing potential for promotion and application in industrial sample detection. The quantitative correlation between amorphous content and stability was successfully established in this study, offering a novel method for a quality stability assessment of atorvastatin calcium drug substances. 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: Tegoprazan (TPZ) is a potassium-competitive acid blocker (P-CAB) used to treat conditions such as gastroesophageal reflux disease, peptic ulcer, and Helicobacter pylori infection. It exists in three solid forms: amorphous, Polymorph A, and Polymorph B. This study investigates the molecular basis of polymorph selection, focusing on conformational bias and solvent-mediated phase transformations (SMPTs). Methods: The conformational energy landscapes of two TPZ tautomers were constructed using relaxed torsion scans with the OPLS4 force field and validated by nuclear Overhauser effect (NOE)-based nuclear magnetic resonance (NMR). Hydrogen-bonded dimers were analyzed using DFT-D. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility, and slurry tests were conducted using methanol, acetone, and water. Kinetic profiles were modeled with the Kolmogorov–Johnson–Mehl–Avrami (KJMA) equation. Results: Polymorph A was thermodynamically stable across all analyses. Both amorphous TPZ and Polymorph B converted to A in a solvent-dependent manner. Methanol induced direct A formation, while acetone showed a B → A transition. Crystallization was guided by solution conformers and hydrogen bonding. Conclusions: TPZ polymorph selection is governed by solution-phase conformational preferences, tautomerism, and solvent-mediated hydrogen bonding. DFT-D and NMR analyses showed that protic solvents favor the direct crystallization of stable Polymorph A, while aprotic solvents promote the transient formation of metastable Polymorph B. Elevated temperatures and humidity accelerate polymorphic transitions. This crystal structure prediction (CSP)-independent strategy offers a practical framework for rational polymorph control and the mitigation of disappearing polymorph risks in tautomeric drugs. Full article

This study examined the relationship between microhardness, morphology, and phase composition of dental yttria-stabilized tetragonal zirconia polycrystals (Y-TZP), which directly impact their long-term clinical performance and durability. The primary objective was to investigate the effects of yttria content and polishing on the surface properties and hardness of these materials. Samples from ZirCAD Prime, Cercon ht ML, ZIRCONIA YML, and ZirCAD LT were analyzed using Vickers hardness testing, Powder X-ray Diffraction (PXRD), and Scanning Electron Microscopy (SEM). SEM analysis revealed a gradual increase in grain size and porosity with higher yttria content in unpolished samples. Polishing resulted in a relatively uniform surface morphology with observable striations across all samples, subsequently leading to similar Vickers hardness values for all polished samples. PXRD and SEM analyses identified that these similar hardness values were likely due to the predominant monoclinic phase on the surface, induced by polishing. These findings underscore the significant influence of yttria content and polishing on Y-TZP microstructure and surface hardness, highlighting their critical role in the long-term success and clinical applicability of dental restorations. Full article

The objective of the current research is to investigate the role of Neusilin US2 as a porous carrier for improving the drug loading and stability of Ezetimibe (EZB) by hot melt extrusion (HME). The amorphous solid dispersions (ASDs) were developed from 10–40% of drug loading using Kollidon VA 64 (Copovidone) as a polymer matrix and Neusilin US2 as a porous carrier. The solid-state characterization of EZB was studied using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). The formulation blends were characterized for flow properties, and CTC (compressibility, tabletability, compactibility) profile. The in-vitro drug release profiles were studied in 0.1 N HCl (pH 1.2). The incorporation of Neusilin US2 has facilitated the development of ASDs up to 40% of drug loading. The CTC profile has demonstrated excellent tabletability for the ternary (EZB, copovidone and Neusilin) dispersions over binary dispersion (EZB and copovidone) formulations. The tablet formulations with binary (20%) and ternary (30% and 40%) dispersions have demonstrated complete dissolution of the drug in 30 min in 0.1 N HCl (pH 1.2). The incorporation of copovidone has prevented the recrystallization of the drug in the solution state. Upon storage of formulations at accelerated conditions, the stability of ternary dispersion tablets was preserved attributing to the entrapment of the drug within Neusilin pores thereby inhibiting molecular mobility. Based on the observations, the current research concludes that it is feasible to incorporate Neusilin US2 to improve the drug loading and stability of ASD systems. Full article

In this study, a novel adsorbent, UiO-66-H₃IMDC, was successfully prepared by functionalizing UiO-66 with imidazole-4,5-dicarboxylic acid (H3IMDC). The effective functionalization of H₃IMDC on UiO-66 was confirmed by powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The relationships between the adsorption of U(VI) on UiO-66-H₃IMDC and the contact time, the pH of the solution, as well as the initial concentration of U(VI) were investigated. Additionally, the selective adsorption of U(VI) by UiO-66-H₃IMDC and its cyclic regeneration performance were also studied. The results demonstrate that the UiO-66-H₃IMDC adsorbent exhibits excellent adsorption performance for uranium in aqueous solutions. Full article

This study reports the discovery and structural characterization of a novel polymorph, designated as Form III, of Alclometasone dipropionate, a corticosteroid commonly used in the treatment of inflammatory dermatoses. Form III was obtained by modifying the crystallization conditions reported in prior art and was thoroughly characterized using Powder X-ray Diffraction (PXRD), Fourier Transform Infrared (FT-IR) spectroscopy, melting-point determination, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), including its first derivative (DTG), optical microscopy, and Scanning Electron Microscopy (SEM). In parallel, pure Form II, previously observed only in mixtures with Form I, was successfully isolated and characterized using the same analytical techniques. Both forms were compared in terms of structural, thermal, and morphological properties. PXRD analysis revealed that Form III crystallizes in a triclinic system; FT-IR spectroscopy revealed unique vibrational signatures, and microscopy showed rod-like crystal morphology. The discovery of Form III expands the current understanding of the solid-state landscape of Alclometasone dipropionate and opens opportunities for the identification of new industrial purification methods for the compound. Full article

Background/Objectives: Chronic lung diseases are among the leading causes of death worldwide. In the treatment of these diseases, non-steroidal anti-inflammatory drugs can be effective. We have previously developed an excipient formulation alongside a modern manufacturing protocol, which we aim to further investigate. We have chosen two new model drugs, meloxicam (MX) and its water-soluble salt, meloxicam-potassium (MXP). The particles in dry powder inhaler (DPI) formulation were expected to have a spherical shape, fast drug release, and good aerodynamic properties. Methods: The excipients were poloxamer-188, mannitol, and leucine. The samples were prepared by spray drying, preceded by solution preparation and wet grinding. Particle size was determined by laser diffraction, shape by scanning electron microscopy (SEM), crystallinity by powder X-ray diffraction (PXRD), interactions by Fourier-transform infrared spectroscopy (FT-IR), in vitro drug dissolution by paddle apparatus, and in vitro aerodynamic properties by Andersen cascade impactor and Spraytec^® device. Results: We achieved the proper particle size (<5 μm) and spherical shape according to laser diffraction and SEM. The XRPD showed partial amorphization. FT-IR revealed no interaction between the materials. During the in vitro dissolution tests, more than 90% of MX and MXP were released within the first 5 min. The best products exhibited an aerodynamic diameter of around 4 µm, a fine particle fraction around 50%, and an emitted fraction over 95%. The analysis by Spraytec^® supported the suitability for lung targeting. Conclusions: The developed preparation process and excipient system can be applied in the development of different drugs containing DPIs. Full article

Background/Objectives: Mometasone furoate (MF) is a topical corticosteroid used to reduce allergic and inflammation symptoms. In this study, MF was incorporated into the hydrophobic cavities of γ-cyclodextrin metal-organic frameworks (CD-MOFs) to prepare MF@MOF powders for nasal delivery. Methods: MF@MOF particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetry. A transparent biomimetic model of the human nasal cavity was produced by 3D printing and used to evaluate intra-nasal depositions patterns. Results: Drug loading was optimized by incubating MF with a CD-MOF at a ratio of 4% for 1 h at 40 °C, and the cubic morphology and particle size of the nanoparticles were not altered using an incubation method. PXRD and FTIR analyses confirmed the successful loading of MF into the CD-MOF. Using a 3D biomimetic nasal cavity model, a 30° administration angle was found to result in reduced drug accumulation in the nasal vestibule and enhanced deposition in the respiratory and olfactory regions, compared with administration at 45°. Approximately 51% of the drug reached the respiratory zone in the model of the nasal cavity from male subjects, while almost 60% of the drug reached this zone in the model associated with female subjects. Compared with nasal sprays, nasal powder sprays had less deposition in the nasal vestibule and more deposits in the middle and inferior nasal concha. Conclusions: MF@MOF is suitable for intranasal administration. Delivery of MF as a nasal powder shows potential in the treatment of chronic rhinosinusitis. Full article

This study aims to describe the triphylite (LiFe²⁺PO₄) from Li-bearing pegmatites from the Conțu-Negovanu area (Southern Carpathians, Romania). Thus, for the first time in this area, using four analytical methods, i.e., electron micro-probe analysis (EMPA), polarized optical microscopy (POM), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (p-XRD), the authors have succeeded in isolating the triphylite from the isomorphous triphylite–lithiophilite series. In addition, in the Conțu-Negovanu area, two new minerals were identified and described for the first time in pegmatites from this area: Fe-rich gatehouseite and wolfeite. The use of EMPA allowed for the tentative calculation of empirical formulae for these secondary phosphate minerals. Full article

Partial reduction of transition metal oxides via defect engineering is a promising strategy to enhance their electronic and photocatalytic properties. In this study, we systematically explored the mechanochemical reduction of Nb₂O₅ using LiBH₄ and NaBH₄ as reducing agents. Electron paramagnetic resonance (EPR) spectroscopy confirmed a successful partial reduction of the oxide, as seen by the presence of unpaired electrons. Interestingly, larger hydride concentrations did not necessarily enable a higher degree of reduction as large amounts of boron hydrides acted as a buffer material and thus hindered the effective transfer of mechanical energy. Powder X-ray diffraction (PXRD) and ⁷Li solid-state NMR spectroscopy indicated the intercalation of Li⁺ into the Nb₂O₅ lattice. Raman spectroscopy further revealed the increased structural disorder, while optical measurements showed a decreased band gap compared with pristine Nb₂O₅. The partially reduced samples showed significantly enhanced photocatalytic performance for methylene blue degradation relative to the unmodified oxides. Full article

The physical stability, molecular mobility, and appearance of nanocrystalline resveratrol in a polyvinylpyrrolidone (PVP) matrix were investigated. Two formulations with resveratrol loadings of 30% and 50% were prepared and characterized using powder X-ray diffraction (PXRD) and time-domain nuclear magnetic resonance (TD-NMR). Samples were studied over time (up to 300 days post-preparation), across temperatures (80–300 K), and under varying humidity conditions (0% and 75% relative humidity). The results demonstrate that the 30% resveratrol–PVP sample is a homogeneous amorphous solid dispersion (ASD), while the 50% resveratrol–PVP sample contained resveratrol nanocrystals measuring about 40 nm. NMR measurements and molecular dynamics (MD) simulations revealed that incorporation of resveratrol into the polymer matrix modifies the system’s dynamics and mobility compared to the pure PVP polymer. Additionally, MD simulations analyzed the hydrogen bonding network within the system, providing insights for a better understanding of the physical stability of the ASD under different conditions. Full article