Search Results (34)

Background/Objectives: This study investigates the stabilisation mechanisms of azelaic acid nanosuspensions (AZA-NS) prepared by wet media milling (WMM) using hydroxypropyl methylcellulose (HPMC) and chitosan as stabilisers. The aim was to elucidate the physical interactions relevant for stabilisation and to evaluate the effectiveness of a dual stabiliser approach to improve AZA-NS stability. Methods: AZA-NS were characterised using Fourier transform infrared spectroscopy (FTIR) to evaluate the chemical interactions, differential scanning calorimetry (DSC) for thermal properties, atomic force microscopy (AFM) to analyse the adsorption of the stabiliser on the AZA surface and X-ray diffraction (XRD) to evaluate the crystallinity. Contact angle and immersion studies were performed to evaluate wettability, and alternative stabilisers were tested for comparison. Results: Highly concentrated AZA-NS (up to 20% drug loading) were successfully produced with particle sizes between 326.8 and 541.2 nm, which are in the optimal range for follicular drug delivery. FTIR confirmed stabilisation by adsorption and not by chemical interaction. DSC revealed a melting point depression, indicating a partial disorder of the crystal lattice. AFM imaging showed different adsorption patterns for HPMC and chitosan, suggesting better surface coverage compared to alternative stabilisers. XRD confirmed the retention of the AZA crystalline form after milling. Contact angle and immersion studies showed improved wettability due to the synergistic effects of HPMC and chitosan. Alternative stabilisers showed suboptimal performance, highlighting the superior stabilising potential of the HPMC–chitosan combination. Conclusions: This study provides important insights into the dual stabilisation mechanisms and highlights the importance of combining steric and electrostatic stabilisers for the formulation of stable nanosuspensions of medium soluble drugs such as AZA. These results support the development of optimised nanosuspensions with increased stability and improved pharmaceutical applicability. Full article

Melting point depressants (MPDs) are required to lower the melting point of filler for brazing. In this study, Zr was used as the MPD, and powder filler was prepared by adjusting the Zr and Mo content referring to Thermo-Calc calculations. The prepared filler was used to braze a high-Mo Ni₃Al-based single crystal superalloy, IC21, for 1200 °C/30 min. The effects of adjusting the Zr and Mo content on the microstructure and tensile properties of the joint were investigated. The increase in Zr content promotes the formation of Ni₇Zr₂ in the joint, leading to a decrease in the tensile strength of the joint. The increase in Mo content forms diffusion barriers between the BM and filler, resulting in an enhancement in the tensile strength of the joint. However, continued increases in Mo content leads to an increase in the P-topologically close packed phase, causing a decline in the tensile strength of the joint. When the Zr content was (11.8–12.2) wt.% and the Mo content was (7.3–7.7) wt.%, the tensile strength of the joint at 980 °C reached a maximum of 550 MPa. This study provides a potential direction for the design of brazing filler composition for high-Mo Ni₃Al-based superalloys. Full article

The obtention of amorphous solid dispersions (ASDs) of mycophenolic acid (MPA) in poly(ε-caprolactone) (PCL) is reported in this paper. An improvement in the bioavailability of the drug is possible thanks to the favorable specific interactions occurring in this system. Differential scanning calorimetry (DSC) was used to investigate the miscibility of PCL/MPA blends, measuring glass transition temperature (T_g) and analyzing melting point depression to obtain a negative interaction parameter, which indicates the development of favorable inter-association interactions. Fourier transform infrared spectroscopy (FTIR) was used to analyze the specific interaction occurring in the blends. Drug release measurements showed that at least 70% of the drug was released by the third day in vitro in all compositions. Finally, preliminary in vitro cell culture experiments showed a decreased number of cancerous cells over the scaffolds containing MPA, presumably arising from the anti-cancer activity attributable to MPA. Full article

In this study, a novel floating, controlled-release and core-shell oral tablet of ketamine hydrochloride (HCl) was produced using a dual extrusion by 3D printing method. A mixture of Soluplus^® and Eudragit^® RS-PO was extruded by a hot-melt extrusion (HME) nozzle at 150–160 °C to fabricate the tablet shell, while a second nozzle known as a pressure-assisted syringe (PAS) extruded the etamine HCl in carboxymethyl cellulose gel at room temperature (25 °C) inside the shell. The resulting tablets were optimized based on the United States pharmacopeia standards (USP) for solid dosage forms. Moreover, the tablet was characterized using Fourier-transform infrared (FTIR) spectrum, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and buoyancy techniques. The results showed a desired dissolution profile for a 100% infill optimized tablet with total drug release (100%) during 12 h. Weight variation and content uniformity of the tablets achieved the USP requirements. SEM micrographs showed a smooth surface with acceptable layer diameters. According to the FTIR analysis, no interference was detected among peaks. Based on DSC analysis, the crystallinity of ketamine HCl did not change during melt extrusion. In conclusion, the floating controlled-release 3D-printed tablet of ketamine HCl can be a promising candidate for management of refractory depressions and chronic pain. Additionally, the additive manufacturing method enables the production of patient-tailored dosage with tunable-release kinetics for personalized medicine in point-of care setting. Full article

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul^® MCM, Gelucire^® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus^® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes. Full article

The Sample Analysis at Mars-Evolved Gas Analyzer (SAM-EGA) on the Curiosity rover detected hydrogen chloride (HCl) and sulfur dioxide (SO₂) gas evolutions above 600 °C and 700 °C, respectively, from several drilled rock and soil samples collected in Gale crater, which have been attributed to NaCl and Mg sulfates. Although NaCl and Mg sulfates do not evolve HCl or SO₂ within the SAM temperature range (<~870 °C) when analyzed individually, they may evolve these gases at <870 °C and become detectable by SAM-EGA when mixed. This work aims to determine how Mg sulfate and NaCl interact during heating and how that affects evolved HCl and SO₂ detection temperatures in SAM-EGA. Solid mixtures of NaCl and kieserite were analyzed using a thermogravimeter/differential scanning calorimeter furnace connected to a quadrupole mass spectrometer, configured to operate under similar conditions as SAM, and using X-ray diffraction of heated powders. NaCl analyzed individually did not evolve HCl; however, NaCl/kieserite mixtures evolved HCl releases with peaks above 600 °C. The results suggested that kieserite influenced HCl production from NaCl via two mechanisms: (1) kieserite depressed the melting point of NaCl, making it more reactive with evolved water; and (2) SO₂ from kieserite decomposition reacted with NaCl and water (i.e., Hargreaves reaction). Additionally, NaCl catalyzed the thermal decomposition of kieserite, such that the evolved SO₂ was within the SAM-EGA temperature range. The results demonstrated that SAM-EGA can detect chlorides and Mg sulfates when mixed due to interactions during heating. These phases can provide information on past climate and mineral formation conditions. Full article

The Si atom diffusion behavior in Ni-based superalloys was evaluated based on first-principles calculations. Also, the site occupation of Si atoms as the melting point depressant elements in Cr, Mo, and W atom doped γ-Ni and γ′-Ni₃Fe supercells was discussed and Si atom diffusion behaviors between both adjacent octahedral interstices were analyzed. Calculation results indicated that formation enthalpy (∆H_f) was decreased, stability was improved by doping alloying elements Cr, Mo, and W in γ-Ni and γ′-Ni₃Fe supercells, Si atoms were more inclined to occupy octahedral interstices and the diffusion energy barrier was increased by increasing the radius of the doped alloy element. Especially, two diffusion paths were available for Si atoms in the γ′-Ni₃Fe and Si diffusion energy barrier around the shared Fe atoms between adjacent octahedral interstices and was significantly lower than that around the shared Ni atoms. The increase of interaction strength between the doped M atom/octahedron constituent atom and Si atom increased Si atom diffusion and decreased the diffusion energy barrier. The Si atom diffusion behavior provides a theoretical basis for the phase structure evolution in wide-gap brazed joints. Full article

The joining zone includes three main parts, which comprise an isothermal solidification zone (ISZ), the athermal solidification zone (ASZ), and a diffusion affected zone (DAZ). Field emission scanning electron microscopy (FESEM) was used here to observe the microstructure equipped with ultra-thin window energy dispersive X-ray spectrometer (EDS) system. Additionally, electrochemical impedance spectroscopy (EIS) and cyclic potentiodynamic polarization tests were conducted to evaluate the effect of the DB process on the corrosion resistance of the Inconel 625 superalloy. In the bonding time period, some Mo- and Cr-rich boride precipitations and Ni-rich γ-solid solution phases with hardened alloy elements, such as Mo and Cr, formed in DAZ and ASZ, respectively, because of the inter-diffusion of melting point depressants (MPD). Moreover, during cooling cycles, Ni-Cr-B, Ni-Mo-B, Ni-Si-B, and Ni-Si phase compounds were formed in the ASZ area at 1110–850 °C. The DAZ area developed by borides compound with cubic, needle, and grain boundary morphologies. The corrosion tests indicated that the DB process led to a reduction in the passive region and increased the sensitivity to pitting corrosion. Full article

Ionic liquid 1-butyl-3-methylimidazolium chloride [BMIM][Cl] was used to prepare cellulose (CELL), cellulose/polycaprolactone (CELL/PCL), cellulose/polycaprolactone/keratin (CELL/PCL/KER), and cellulose/polycaprolactone/keratin/ground calcium carbonate (CELL/PCL/KER/GCC) biodegradable mulch films. Attenuated Total Reflectance Fourier-Transform Infrared (ATR-FTIR) spectroscopy, optical microscopy, and Field-Emission Scanning Electron Microscopy (FE-SEM) were used to verify the films’ surface chemistry and morphology. Mulch film made of only cellulose regenerated from ionic liquid solution exhibited the highest tensile strength (75.3 ± 2.1 MPa) and modulus of elasticity of 944.4 ± 2.0 MPa. Among samples containing PCL, CELL/PCL/KER/GCC is characterized by the highest tensile strength (15.8 ± 0.4 MPa) and modulus of elasticity (687.5 ± 16.6 MPa). The film’s breaking strain decreased for all samples containing PCL upon the addition of KER and KER/GCC. The melting temperature of pure PCL is 62.3 °C, whereas that of CELL/PCL film has a slight tendency for melting point depression (61.0 °C), which is a characteristic of partially miscible polymer blends. Furthermore, Differential Scanning Calorimetry (DSC) analysis revealed that the addition of KER or KER/GCC to CELL/PCL films resulted in an increment in melting temperature from 61.0 to 62.6 and 68.9 °C and an improvement in sample crystallinity by 2.2 and 3.0 times, respectively. The light transmittance of all studied samples was greater than 60%. The reported method for mulch film preparation is green and recyclable ([BMIM][Cl] can be recovered), and the inclusion of KER derived by extraction from waste chicken feathers enables conversion to organic biofertilizer. The findings of this study contribute to sustainable agriculture by providing nutrients that enhance the growth rate of plants, and hence food production, while reducing environmental pressure. The addition of GCC furthermore provides a source of Ca²⁺ for plant micronutrition and a supplementary control of soil pH. Full article

Four model polymers, representing (i) amorphous homopolymers (Kollidon K30, K30), (ii) amorphous heteropolymers (Kollidon VA64, KVA), (iii) semi-crystalline homopolymers (Parteck MXP, PXP), and (iv) semi-crystalline heteropolymers (Kollicoat IR, KIR), were examined for their effectiveness in creating posaconazole-based amorphous solid dispersions (ASDs). Posaconazole (POS) is a triazole antifungal drug that has activity against Candida and Aspergillus species, belonging to class II of the biopharmaceutics classification system (BCS). This means that this active pharmaceutical ingredient (API) is characterized by solubility-limited bioavailability. Thus, one of the aims of its formulation as an ASD was to improve its aqueous solubility. Investigations were performed into how polymers affected the following characteristics: melting point depression of the API, miscibility and homogeneity with POS, improvement of the amorphous API’s physical stability, melt viscosity (and associated with it, drug loading), extrudability, API content in the extrudate, long term physical stability of the amorphous POS in the binary drug–polymer system (in the form of the extrudate), solubility, and dissolution rate of hot melt extrusion (HME) systems. The obtained results led us to conclude that the physical stability of the POS-based system increases with the increasing amorphousness of the employed excipient. Copolymers, compared to homopolymers, display greater homogeneity of the investigated composition. However, the enhancement in aqueous solubility was significantly higher after utilizing the homopolymeric, compared to the copolymeric, excipients. Considering all of the investigated parameters, the most effective additive in the formation of a POS-based ASD is an amorphous homopolymer—K30. Full article

The brazing of structural high-temperature-resistant nickel alloys is a predominant method in manufacturing jet engines in the aircraft industry. Ni-Cr-base brazing filler metals (BFMs) containing B and Si as the melting point depressants are used for this purpose. The presence of the latter can lead to the formation of brittle constituents in the joints, decreasing their strength, toughness and creep resistance. The structures of Hastelloy X nickel superalloy joints brazed with Palnicro 36M BFM are presented in this paper along with the mechanical properties of their particular phases as a function of brazing time. Indentation hardness, Martens hardness, reduced modulus and creep coefficient were measured using the instrumented indentation method. The elastic part of the indentation work was also calculated. Pd forms an unlimited solution with Ni, but its high content in BFM does not fundamentally change the general joint structure known from other Ni-superalloy–Ni-BFM systems. However, new Pd-containing phases are emerging. The hardest components were Ni-B and Cr-B boride phases and Pd-Ni-Si phase in MZ and the boundary of DAZ and BM. MZ reduces the plasticity of a joint to the highest extent. The hardness of particular parts in the joints and the elastic portion of the indentation work decreased with the increase in brazing time, while the reduced modulus of the indentation contact and indentation creep increased. The results of indentation creep measurements indicate that all structural components of the joints were less susceptible to creep than the parent material at room temperature. Full article

Deep eutectic solvents (DESs) are a class of green and tunable solvents that can be formed by mixing constituents having very low melting entropies and enthalpies. As types of materials that meet these requirements, plastic crystalline materials (PCs) with highly symmetrical and disordered crystal structures can be envisaged as promising DES constituents. In this work, three PCs, namely, neopentyl alcohol, pivalic acid, and neopentyl glycol, were studied as DES constituents. The solid–plastic transitions and melting properties of the pure PCs were studied using differential scanning calorimetry. The solid–liquid equilibrium phase diagrams of four eutectic systems containing the three PCs, i.e., L-menthol/neopentyl alcohol, L-menthol/pivalic acid, L-menthol/neopentyl glycol, and choline chloride/neopentyl glycol, were measured. Despite showing near-ideal behavior, the four studied eutectic systems exhibited depressions at the eutectic points, relative to the melting temperatures of the pure constituents, that were similar to or even larger than those of strongly nonideal eutectic systems. These findings highlight that a DES can be formed when PCs are used as constituents, even if the eutectic system is ideal. Full article

The melting behaviour of the triblock polymers, Pluronic F38, F68, F77, F108, and F127, was investigated in pressurised CO₂ and in the presence of menthol. The melting points of the polymers combined with 0, 10, 25, and 50 wt% of menthol were studied at atmospheric pressure and compared with those at 10 and 20 MPa in supercritical carbon dioxide (scCO₂). The highest melting point depressions of 16.8 ± 0.5 °C and 29.0 ± 0.3 °C were observed at 10 and 20 MPa, respectively. The melting point of triblock polymers in pressurised CO₂ was found to be dependent on molecular weight, poly(propylene oxide) (PPO) content, and menthol percentage. The melting point of most of the polymers studied in this work can be reduced to room temperature, which can be pivotal to the formulation development of thermolabile substances using these polymers. Full article

Antifreeze proteins (AFPs) or thermal hysteresis (TH) proteins are biomolecular gifts of nature to sustain life in extremely cold environments. This family of peptides, glycopeptides and proteins produced by diverse organisms including bacteria, yeast, insects and fish act by non-colligatively depressing the freezing temperature of the water below its melting point in a process termed thermal hysteresis which is then responsible for ice crystal equilibrium and inhibition of ice recrystallisation; the major cause of cell dehydration, membrane rupture and subsequent cryodamage. Scientists on the other hand have been exploring various substances as cryoprotectants. Some of the cryoprotectants in use include trehalose, dimethyl sulfoxide (DMSO), ethylene glycol (EG), sucrose, propylene glycol (PG) and glycerol but their extensive application is limited mostly by toxicity, thus fueling the quest for better cryoprotectants. Hence, extracting or synthesizing antifreeze protein and testing their cryoprotective activity has become a popular topic among researchers. Research concerning AFPs encompasses lots of effort ranging from understanding their sources and mechanism of action, extraction and purification/synthesis to structural elucidation with the aim of achieving better outcomes in cryopreservation. This review explores the potential clinical application of AFPs in the cryopreservation of different cells, tissues and organs. Here, we discuss novel approaches, identify research gaps and propose future research directions in the application of AFPs based on recent studies with the aim of achieving successful clinical and commercial use of AFPs in the future. Full article

Here, we report the synthesis and experimental characterization of three drug-drug eutectic mixtures of drug aminoglutethimide (AMG) with caffeine (CAF), nicotinamide (NIC) and ethenzamide (ZMD). The eutectic mixtures i.e., AMG-CAF (1:0.4, molar ratio), AMG-NIC (1:1.9, molar ratio) and AMG-ZMD (1:1.4, molar ratio) demonstrate significant melting point depressions ranging from 99.2 to 127.2 °C compared to the melting point of the drug AMG (151 °C) and also show moderately higher aqueous solubilities than that of the AMG. The results presented include the determination of the binary melt phase diagrams and accompanying analytical characterization via X-ray powder diffraction, FT-IR spectroscopy and scanning electron microscopy. Full article