Hydroxypropyl methyl cellulose acetate succinate (HPMCAS) is one of the polymers of choice in formulating amorphous solid dispersions (ASDs) and helps to sustain high levels of drug supersaturation by delaying drug crystallization. Herein, the impact of HPMCAS chemistry on the solution crystallization kinetics of a fast-crystallizing lipophilic drug, posaconazole (PCZ), from the aqueous bulk phase and the drug-rich phase generated by liquid-liquid phase separation (LLPS), was studied. Three grades of HPMCAS: L, M, and H, which differ in the degree of acetyl and succinoyl substitution (A/S ratio), were compared. The influence of the polymers on the nucleation induction time, and LLPS concentration of PCZ, as well as the size, ζ-potential and composition of the nano-sized drug-rich phase was determined. An increase in the nucleation induction time was observed with an increase in the polymer A/S ratio. A blue shift in the fluorescence emission spectrum of PCZ suggested a greater extent of interaction between PCZ and HPMCAS with an increase in the A/S ratio. More polymer partitioning into the drug-rich phase was also observed with an increase in the A/S ratio, resulting in smaller droplets. A greater extent of ionization of HPMCAS upon increasing the pH from 5.5 to 7.5 decreased the hydrophobicity of the polymer resulting in shorter nucleation induction times. The phase behavior of PCZ in ASD release studies was consistent with these observations, where the shortest duration of supersaturation was observed with the L grade. Although the H grade provided the best inhibition of crystallization, complete release was only observed at higher pH. HPMCAS grade thus influences the kinetics of PCZ crystallization following release from an ASD, as well as the extent of release at physiologically relevant pH conditions. This study provides insights into the role of HPMCAS chemistry and ionization as factors influencing its ability to act as a crystallization inhibitor.

Advancing cathode materials is crucial for the broader application of aqueous zinc-ion batteries (ZIBs) in energy storage systems. This study presents amorphous H/VO4 (HVO), a novel cathode material engineered by substituting H+ for Mg2+ in Mg2VO4 (MgVO), designed to enhance performance of ZIBs. Initial exploration of MgVO through ab initio molecular dynamics (AIMD) simulations and density functional theory (DFT) calculations revealed a favorable Mg2+ and Zn2+ exchange mechanism. This mechanism notably reduces electrostatic interactions and facilitates ion diffusion within the host lattice. Building upon these findings, in this work, theoretical calculations analysis indicated that amorphous HVO offers a higher diffusion coefficient for Zn2+ ions and fewer electrostatic interactions compared to its crystalline MgVO precursor. Subsequent empirical validation is achieved by synthesizing amorphous HVO using a rapid ion-exchange process, effectively replacing Mg2+ with H+ ions. The synthesized amorphous HVO demonstrated 100% capacity retention after 18000 cycles at a current density of 2 A g-1 and exhibited exceptional rate performance. These findings underscore the significant potential of HVO cathodes to enhance the durability and efficiency of aqueous ZIBs, positioning them as promising candidates for future energy storage technologies.

Mesoporous silica particles (MSPs) have been investigated as potential carriers to increase the apparent solubility and dissolution rate of poorly water-soluble drugs by physically stabilising the amorphous nature of the loaded drug. In preparing such systems, it is recognized that the loading method has a critical impact on the physical state and performance of the drug. To date, there has been very limited investigation into the use of electrospraying for loading drugs into mesoporous silica. In this study, we further explore the use of this approach, in particular as a means of producing amorphous and high drug-loaded MSPs; the study includes an investigation of the effect of drug loading and MSP concentration on the formulation performance and process. A comparison with rotary evaporation, a more widely utilised loading technique, was conducted to assess the relative effectiveness of electrospraying. The physical state of the drug in the formulations was assessed using powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The drug release profiles were determined by a comparative in vitro drug release test. Electrospraying successfully produced formulations containing amorphous drug even at a high drug loading. In contrast, while itraconazole was present in amorphous form at the lower drug-loaded formulations produced by rotary evaporation, the drug was in the crystalline state at the higher loadings. The percentage of drug released was enhanced up to ten times compared to that of pure itraconazole for all the formulations apart from the highest loaded (crystalline) formulation prepared by rotary evaporation. Supersaturation for at least six hours was maintained by the formulations loaded with up to 30 mg/mL itraconazole produced by electrospraying. Overall, the results of this study demonstrate that electrospraying is capable of producing amorphous drug-loaded MSPs at high loadings, with associated favourable release characteristics. A comparison with the standard rotary evaporation approach indicates that electrospraying may be more effective for the production of higher loadings of amorphous material.

Amorphous Indomethacin has enhanced bioavailability over its crystalline forms, yet amorphous forms can still possess a wide variety of structures. Here, Empirical Potential Structure Refinement (EPSR) has been used to provide accurate molecular models on the structure of five different amorphous Indomethacin samples, that are consistent with their high-energy X-ray diffraction patterns. It is found that the majority of molecules in amorphous Indomethacin are non-bonded or bonded to one neighboring molecule via a single hydrogen bond, in contrast to the doubly bonded dimers found in the crystalline state. The EPSR models further indicate a substantial variation in hydrogen bonding between different amorphous forms, leading to a diversity of chain structures not found in any known crystal structures. The majority of hydrogen bonds are associated with the carboxylic acid group, although a significant number of amide hydrogen bonding interactions are also found in the models. Evidence of some dipole-dipole interactions are also observed in the more structurally ordered models. The results are consistent with a distribution of Z-isomer intramolecular type conformations in the more disordered structures, that distort when stronger intermolecular hydrogen bonding occurs. The findings are supported by 1H and 2H NMR studies of the hydrogen bond dynamics in amorphous Indomethacin.

Low-frequency peaks in the Raman spectra of amorphous poly(ether ether ketone) (PEEK) were investigated. An amorphous sample with zero crystallinity, as confirmed by wide-angle X-ray diffraction, was used in this study. In a previous study, two peaks were observed in the low-frequency Raman spectra of the crystallized samples. Among these, the peaks at 135 cm-1 disappeared for the amorphous sample. Meanwhile, for the first time, the peak at 50 cm-1 was observed in the crystallized sample. Similar to the peak at 135 cm-1, the peak at 50 cm-1 disappeared in the amorphous state, and its intensity increased with increasing crystallinity. The origins of the two peaks were associated with the Ph-CO-Ph-type intermolecular vibrational modes in the simulation. This suggests that the Ph-CO-Ph vibrational mode observed in the low-frequency region of PEEK was strongly influenced by the intermolecular order.

Improvement in drug solubility is a major challenge for developing pharmaceutical products. It was demonstrated earlier that aqueous solubilities of weakly basic drugs could be increased greatly by interaction with weak acids that would not form salts with the drugs, and the highly concentrated solutions thus produced converted to amorphous solids upon drying. The technique was called acid-base supersolubilization (ABS). The current investigation explored whether the ABS principle could also be applied to weakly acidic drugs. By taking flurbiprofen (pKa 4.09; free acid solubility 0.011 mg/mL) as the model weakly acidic drug and tromethamine, lysine, meglumine, and NaOH as bases, it was studied which of the bases would result in ABS. While in the presence of NaOH and tromethamine, flurbiprofen converted to salts having aqueous solubility of 11-19 mg/mL, the solubility increased to > 399 mg/mL with lysine and > 358 mg/mL with meglumine, producing supersolubilization. However, crystallization of lysine salt was observed with time, followed by some decrease in solubility after reaching maximum solubility with lysine. In contrast, the supersolubilization was maintained with meglumine, and no crystallization of meglumine salt was observed. Upon drying, flurbiprofen-meglumine solutions produced amorphous materials that dissolved rapidly and produced high drug concentrations in aqueous media. Thus, the ABS principle also applies to acidic drugs depending on the weak base used.

Resveratrol (RES) has demonstrated advantages as anti-cancer, anti-inflammatory, blood sugar-lowering agent and as cardioprotective agent, among others. Despite RES therapeutic advantages its use in pharmaceutical applications is limited by its low oral bioavailability, mainly due to its poor water solubility. Formulation of poorly water-soluble compound as solid dispersion (SD) converts a crystalline into a more soluble in water amorphous drug. Lyophilization or freeze-drying is a process in which water, an organic solvent, or a co-solvent system is frozen, followed by its removal from the sample, initially by sublimation (primary drying) and then by desorption (secondary drying). This study aimed the development and optimization of a bulk freeze-drying cycle by critical process parameters assessment in each phase to prepare a RES third-generation SD, containing Eudragit E PO as hydrophilic polymer at 1:2 ratio, and Gelucire 44/14 as surfactant at 16 % (w/w) to RES, using a tert-butanol (TBA)/Acetate buffer pH 4.5 (75:25) co-solvent system. A RES third-generation SD with good appearance, not cracked, collapsed, or melted was prepared by an optimized and robust bulk lyophilization process. A physicochemical characterization confirmed the conversion of RES to the amorphous state in the SD and formulation stability after 1 month at 40 °C/75 % RH. Increased solubility and higher dissolution rate compared with pure RES were also obtained.

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.

Carbonaceous materials hydrothermally produced using waste biomass have small specific surface areas (SSA) and poor porosity properties. In this study, we prepare a novel carbonaceous material with excellent porosity properties by suppressing the formation of a secondary char phase (spheres) and promoting biomass hydrolysis by controlling the hydrothermal conditions. Rice husk powders, as the starting material, are hydrothermally treated using acidic solvents of different types and concentrations at 180 °C. The surfaces of the samples hydrothermally prepared using the acidic solvents have no spheres. In the case of 0.1-0.2 mol L-1 hydrochloric acid (HA), the amorphous carbonaceous materials contain numerous mesopores and exhibit a larger SSA (approximately 100 m2 g-1) than those prepared using acetic acid and distilled water. An increase in the hydrothermal temperature reduces the porosity properties of the materials. Finally, the high-porosity amorphous carbonaceous material showed excellent trimethylamine adsorption ability.

Background Bioactive glass, which can form strong bonds with tissues, particularly bones, has become pivotal in tissue engineering. Incorporating biologically active ions like selenium enhances its properties for various biomedical applications, including bone repair and cancer treatment. Selenium\'s antioxidative properties and role in bone health make it a promising addition to biomaterial. Aim The present study was aimed at the preparation and characterization of selenium-doped bioglass. Materials and methods Tetraethyl orthosilicate (TEOS) was mixed with ethanol, water, and nitric acid to form a silica network and then supplemented with calcium nitrate, selenium acid sodium nitrate, and orthophosphoric acid. Sequential addition ensured specific functionalities. After sintering at 300 °C for three hours, the viscous solution transformed into powdered selenium-doped bioglass. Characterization involved scanning electron microscope (SEM) for microstructure analysis, attenuated total reflection infrared spectroscopy (ATR-IR) for molecular structure, and X-ray diffraction (XRD) for crystal structure analysis. Results SEM analysis of selenium-doped bioglass reveals a uniform distribution of selenium dopants in an amorphous structure, enhancing bioactivity through spherical particles with consistent size, micro-porosity, and roughness, facilitating interactions with biological fluids and tissues. ATR-IR analysis shows peaks corresponding to Si-O-Si and P-O bonds, indicating the presence of phosphate groups essential for biomedical applications within the bioglass network. XRD analysis confirms the amorphous nature of selenium-doped bioglass, with shifts in diffraction peaks confirming selenium incorporation without significant crystallization induction. Conclusion The selenium-infused bioglass displays promising versatility due to its amorphous structure, potentially enhancing interactions with biological fluids and tissues. Further research is needed to assess its impact on bone regeneration activity.