Investigation of the Influence of Anti-Solvent Precipitation Parameters on the Physical Stability of Amorphous Solids.

Amorphous solids exhibit enhanced solubility and dissolution rates relative to their crystalline counterparts. However, attaining optimal bioavailability presents a challenge, primarily due to the need to maintain the physical stability of amorphous solids. Moreover, the precise manner in which precipitation parameters, including the feeding rate of the anti-solvent, agitation speed, and aging time, influence the physical stability of amorphous solids remains incompletely understood. Consequently, this study aimed to investigate these three parameters during the precipitation process of the anticancer drug, nilotinib free base. The physical stability of the resultant samples was evaluated by employing characterization techniques including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), focused beam reflectance measurement (FBRM), and data analysis methods such as pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA). This study's findings indicated that amorphous solids exhibited the greatest physical stability under particular conditions, namely a feeding rate of 5 mL/min, an agitation speed of 500 rpm, and an aging time of 10 min. Furthermore, the physical stability of the amorphous solids was primarily influenced by particle size and distribution, molecular interactions, microstructure, surface area, and interfacial energy. Notably, the parameters involved in the anti-solvent precipitation process, including the feeding rate of the anti-solvent, agitation speed, and aging time, exerted a significant impact on these factors. Consequently, they directly affected the physical stability of amorphous solids. Hence, this study comprehensively elucidated the mechanistic influence of these operational parameters on the physical stability of amorphous solids during the anti-solvent precipitation process.

An Investigation of the Impact of Precipitation Temperature and Filter Cake Thickness on the Physical Stability of Amorphous Solids: A Case Study.

The purpose of this study was to resolve the issue of physical instability in amorphous solid drugs, which can result in unwanted crystallization, affecting solubility and dissolution rates. The focus was on precipitating physically stable amorphous forms of the nilotinib free base, an anticancer drug, by monitoring preparation conditions such as precipitation temperature and filter cake thickness. A comprehensive set of characterization techniques, including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and focused beam reflectance measurement (FBRM), were used. These were supplemented by advanced data analysis methods that incorporated pair distribution function (PDF), reduced crystallization temperature (Rc), and principal component analysis (PCA) to evaluate the physical stability of the amorphous samples. Results emphasized that optimal physical stability was achieved when amorphous solids were prepared at a precipitation temperature of 10 °C and a filter cake thickness of 4 cm. Moreover, the integration of PDF analysis with Rc values was confirmed as an innovative approach for assessing physical stability, thus offering enhanced efficiency and accuracy over conventional accelerated stability testing methods.

The Optimization of Pair Distribution Functions for the Evaluation of the Degree of Disorder and Physical Stability in Amorphous Solids.

The amorphous form of poorly soluble drugs is physically unstable and prone to crystallization, resulting in decreased solubility and bioavailability. However, the conventional accelerated stability test for amorphous drugs is time-consuming and inaccurate. Therefore, there is an urgent need to develop rapid and accurate stability assessment technology. This study used the antitumor drug nilotinib free base as a model drug. The degree of disorder and physical stability in the amorphous form was assessed by applying the pair distribution function (PDF) and principal component analysis (PCA) methods based on powder X-ray diffraction (PXRD) data. Specifically, the assessment conditions, such as the PDF interatomic distance range, PXRD detector type, and PXRD diffraction angle range were also optimized. The results showed that more reliable PCA data could be obtained when the PDF interatomic distance range was 0-15 Å. When the PXRD detector was a semiconductor-type detector, the PDF data obtained were more accurate than other detectors. When the PXRD diffraction angle range was 5-40°, the intermolecular arrangement of the amorphous drugs could be accurately predicted. Finally, the accelerated stability test also showed that under the above-optimized conditions, this method could accurately and rapidly assess the degree of disorder and physical stability in the amorphous form of drugs, which has obvious advantages compared with the accelerated stability test.

Keto-Adamantane-Based Macrocycle Crystalline Supramolecular Assemblies Showing Selective Vapochromism to Tetrahydrofuran.

Here, we report the synthesis of adamantane-based macrocycle 2 by combining adamantane building blocks with π-donor 1,3-dimethoxy-benzene units. An unpredictable keto-adamantane-based macrocycle 3 was obtained by the oxidation of 2 using DDQ as an oxidant. Moreover, a new type of macrocyclic molecule-based CT cocrystal was prepared through exo-wall CT interactions between 3 and DDQ. The cocrystal material showed selective vapochromism behavior towards THF, specifically, among nine volatile organic solvents commonly used in the laboratory. Powder X-ray diffraction; UV-Vis diffuse reflectance spectroscopy; 1H NMR; and single crystal X-ray diffraction analyses revealed that color changes are attributed to the vapor-triggered decomplexation of cocrystals.

Inhibitory action of antimicrobial peptides against the formation of carcinogenic and mutagenic heterocyclic amines in meat.

Thermal processing of meat leads to the development of Maillard's reaction intermediates, and carcinogenic toxicants. For the first time, the effectiveness of three (HX-12A, HX-12B and HX-12C) antimicrobial peptides (AMPs) against the formation of heterocyclic amines (HAs) in chemical and meat model systems. The results showed that AMPs especially 12A and 12C have strong metal chelation potential (48 and 40% at 1 mg/ml) and antioxidant activity (35 and 25% at 1 mg/ml), respectively, which were endorsed by their secondary structure (FTIR analysis) in terms of high ß-sheets (1628 cm-1 and 1672 cm-1) in those AMPs. UPLC-MS analysis revealed that 12A and 12C were the most capable AMPs in MeIQx and PhIP-producing chemical models, respectively, whereas 12B promoted the HAs formation even higher than control. In particular, 12C AMP significantly (P < 0.05) decreased the most abundant carcinogenic HAs (PhIP) up to 90% at 9 mg/100 g of fresh meat, whereas 12A inhibited up to 80% of mutagenic HAs at same level compared to control and 12B. Low Field Nuclear Magnetic Resonance (LF-NMR) test showed that inhibitory effect of 12A and 12C was mediated by means of retaining water (lower T22 and T23 relaxation time) inside the macromolecules. This favorable effect was also evidenced by significantly enhanced tryptophan fluorescent intensity. Finally, based on correlation and principle component analysis, the mechanism of action has been proposed. These outcomes recommend that 12A and 12C are potential AMPs for the attenuation of HAs in thermally processed meat-based products.

Liquid Crystal Droplet-Based Biosensors: Promising for Point-of-Care Testing.

The development of biosensing platforms has been impressively accelerated by advancements in liquid crystal (LC) technology. High response rate, easy operation, and good stability of the LC droplet-based biosensors are all benefits of the long-range order of LC molecules. Bioprobes emerged when LC droplets were combined with biotechnology, and these bioprobes are used extensively for disease diagnosis, food safety, and environmental monitoring. The LC droplet biosensors have high sensitivity and excellent selectivity, making them an attractive tool for the label-free, economical, and real-time detection of different targets. Portable devices work well as the accessory kits for LC droplet-based biosensors to make them easier to use by anyone for on-site monitoring of targets. Herein, we offer a review of the latest developments in the design of LC droplet-based biosensors for qualitative target monitoring and quantitative target analysis.

[Influence of different drying temperatures for solid substrate after fermentation on conidia characteristics of the entomopathogenic fungus Beauveria bassiana].

OBJECTIVE: This study was to evaluate the effect of drying temperature for solid substrate after fermentation on conidia characteristics of entomopathogenic fungus Beauveria bassiana. METHODS: Seven constant or varied temperatures between 28 degrees C and 35 degrees C were designed for drying the solid substrate and the quality of harvested conidia was analyzed. RESULTS: The results showed that the drying treatments at varied temperatures significantly decreased bacterial contamination in the harvested conidia powder. The conidia viability and germination speed were varied with different drying treatments. After drying at 35 degrees C for 5 h, there was no significant difference in viability between the dried and fresh conidia, while the median germination time (9.6 h) of the dried conidia was shortened by 9.3%. The tolerance of conidia to heat and UV radiation was increased by drying treatment. Compared to the drying treatment at a constant temperature at 28 degrees C or 35 degrees C, some varied temperature treatments were in favor of enhancing the stress tolerance of conidia. Drying treatments influenced accumulation of trehalose in harvested conidia, while neither heat resistance nor UV tolerance of conidia was obvious correlation with trehalose level. Optimizing drying temperature could increase the virulence of B. bassiana. After drying at 28 degrees C for 24 h and then 35 degrees C for 2 h or at 35 degrees C for 5 h, the LT(50S) to Myzus persicae at the dose of 370-450 conidia /mm2 were shortened by 10.6 h and 7.5 h, respectively. CONCLUSION: The results suggested that the drying temperature for post-fermentation solid substrate has an important influence on bacterial contamination in the harvested conidia powder, spore viability, stress tolerance and virulence in B. bassiana.