Nondestructive Measurement Technique for Substandard Amoxicillin Based on Thermal Approach.

In this study, we introduce a new nondestructive measurement technique based on a thermal approach for the determination of substandard amoxicillin. The quality control of amoxicillin is critical for patient safety, and one of the essential parameters for its evaluation is the content of the active ingredient. Traditional methods for assessing amoxicillin content are defined by their time-consuming nature, reliance on skilled personnel, and frequent necessity for specific reagents. The proposed device aims to provide a rapid and low-cost alternative that can accurately measure the amoxicillin content without damaging the sample. The method validation results indicate coefficient of determination (R2) exceeding 0.99, with percent recoveries falling within the range of 98.70-103.40%. The calculated values for limit of detection and limit of quantitation were determined to be 28.11 and 85.17 mg/L, respectively. Our experiments employed amoxicillin samples with predetermined concentrations, all of which were below the standard quality. It was observed that the proposed analytical device effectively quantifies the amoxicillin content in aqueous solutions. Each measurement took no more than 10 min, underscoring the efficiency of the analysis process. The experiments were validated through independent testing at the Government Pharmaceutical Organization in Thailand and the department of engineering science in Oxford, which provides strong evidence for the effectiveness and robustness of the technique. Overall, this study demonstrates the feasibility of using a thermal approach for the nondestructive measurement of substandard amoxicillin.

Non-destructive measurement technique for water content in organic solvents based on a thermal approach.

The water content of organic solvents is one of the crucial properties that affect the quality of the products and the efficiency of the manufacturing processes. The established water determination methods such as Karl Fischer titration and gas chromatography require skilled operators, specific reagents, and prolonged measurement time. Thus, they are not suitable for both on-line and in-line applications. In this study, we aim to develop a real-time and low-cost device with reliable accuracy. The proposed device based on a newly developed thermal approach could non-destructively detect the water content in multiple organic solvents at low concentrations with high accuracy and without the use of any specific reagent. Experiments were performed for the determination of water content in organic solvents such as methanol, ethanol, and isopropanol. The results show that the proposed device is feasible for the water content determination in methanol, ethanol, and isopropanol at 0-1% w/w. A Bland-Altman plot to illustrate the differences in measurements between the proposed device and coulometric Karl Fischer titration shows that most of the measurements lie within the limits of agreement where 95% of the differences between the two methods are expected to fall in the range of -0.13% and 0.09%.

Scalable synthesis of favipiravir via conventional and continuous flow chemistry.

Decagram scale synthesis of favipiravir was performed in 9 steps using diethyl malonate as cheap starting material. Hydrogenation and bromination steps were achieved by employing a continuous flow reactor. The synthetic process provided a total of 16% yield and it is suitable for larger-scale synthesis and production.

Recent Progress in the Development of HIV-1 Entry Inhibitors: From Small Molecules to Potent Anti-HIV Agents.

Viral entry, the first process in the reproduction of viruses, primarily involves attachment of the viral envelope proteins to membranes of the host cell. The crucial components that play an important role in viral entry include viral surface glycoprotein gp120, viral transmembrane glycoprotein gp41, host cell glycoprotein (CD4), and host cell chemokine receptors (CCR5 and CXCR4). Inhibition of the multiple molecular interactions of these components can restrain viruses, such as HIV-1, from fusion with the host cell, blocking them from reproducing. This review article specifically focuses on the recent progress in the development of small-molecule HIV-1 entry inhibitors and incorporates important aspects of their structural modification that lead to the discovery of new molecular scaffolds with more potency.

Scale-Up Synthesis and In Vivo Anti-Tumor Activity of Curcumin Diethyl Disuccinate, an Ester Prodrug of Curcumin, in HepG2-Xenograft Mice.

Previously, we synthesized curcumin and a succinate ester prodrug of curcumin namely curcumin diethyl disuccinate (CurDD) in the lab scale, which yielded hundred milligrams to few grams of the compounds. CurDD was found to be more stable in a phosphate buffer pH 7.4 and exhibited better cytotoxicity against Caco-2 cells than curcumin. Here, the one-pot syntheses of curcumin and CurDD were scaled up to afford multigram quantities of both compounds for preclinical studies using a 10-L chemical reactor. The key steps for the synthesis of curcumin were the formation of boron-acetylacetone complex and the decomplexation of boron-curcumin complex. The synthesis of CurDD could be achieved via a one-step esterification between curcumin and succinic acid monoethyl ester chloride using 4-(N,N-dimethylamino)pyridine as a catalyst. The synthesized curcumin and CurDD were then investigated and compared for an anti-tumor activity in HepG2-xenograft mice. CurDD could reduce the tumor growth in HepG2-xenograft mice better than curcumin. CurDD also exerted the stronger inhibition on VEGF secretion, COX-2 and Bcl-2 expression and induced higher Bax expression in comparison with curcumin. The results suggest that CurDD is a promising prodrug of curcumin and has a potential to be further developed as a therapeutic agent or an adjuvant for the treatment of hepatocellular carcinoma.