Influence mechanism of excipients on drug crystallization: experimental investigation and model analysis and prediction

The influence of temperature, stirring speed, and excipients on crystal growth kinetics of mesalazine and allopurinol was investigated through experiment and chemical potential gradient model. The results indicated that the Diffusion-Surface Reaction model (DSR (1,2)) showed good performance in modeling API crystal growth kinetics within the ARDs of 4%. Excipients played a crucial role in inhibiting crystal growth in all the systems. It can not only improve the API solubility, but also reduce the crystal growth rate. By comparing diffusion rate and surface-reaction rate constant within the DSR (1,2) model, it was found that the controlling step of mesalazine crystallization was surface-reaction. Allopurinol crystallization was dominated by both surface-reaction and diffusion. Meanwhile, the crystal growth kinetics of mesalazine and allopurinol were predicted successfully with the ARDs of 2.53% and 4.78%. This work provided a mechanistic understanding of polymer influence on the inhibition of API crystal growth.

Estimation of parameters characterizing a steady-state synthesis process with nonlinear microorganism growth kinetics

The paper describes a theoretical basis developed for estimating the parameters of a steady-state biotechnological process characterized by nonlinear microorganism growth kinetics. This study aimed to obtain a common methodological basis for estimating input parameters that determine actual technology implementation, taking into account all possible restrictions on the concentration of incoming substrate Sf (g/l) and dilution rate D (h-1 ). The theory development was based on a mathematical model describing one of the most common processes of lactic acid production. This mathematical model includes three mass balance equations (for biomass, substrate, and product), as well as an equation of microorganism growth kinetics. The study established relations for calculating the ultimate value of the dilution rate D ult at a given Sf , relations for the maximum and minimum values of Sf , as well as Sf and D providing the maximum productivity value QP, g/(l·h), where QP = PD (P – product concentration, g/l). These relations were designed to calculate the parameters of possible process implementation for two options at the same value of QP: two values of D calculated for a given Sf and two values of Sf calculated for a given D. A numerical experiment is described using the constants of the mathematical model confirmed by foreign studies. This numerical experiment is illustrated using an Sf-D dependence pattern determining an acceptable value range for Sf and D, with the separate calculation of parameters according to Sf sections. For each of these sections, calculation formulas are provided. It is concluded that the developed theoretical basis is sufficiently general in nature to be applied to biotechnological processes that involve other kinetic relations, as well as microorganism strains creating by-products and using raw materials that are employed to reproduce the substrate in the process of synthesis.

Biofabrication of ZnO nanoparticles using Acacia arabica leaf extract and their antibiofilm and antioxidant potential against foodborne pathogens

Emergence of multidrug resistant pathogens is increasing globally at an alarming rate with a need to discover novel and effective methods to cope infections due to these pathogens. Green nanoparticles have gained attention to be used as efficient therapeutic agents because of their safety and reliability. In the present study, we prepared zinc oxide nanoparticles (ZnO NPs) from aqueous leaf extract of Acacia arabica. The nanoparticles produced were characterized through UV-Visible spectroscopy, scanning electron microscopy, and X-ray diffraction. In vitro antibacterial susceptibility testing against foodborne pathogens was done by agar well diffusion, growth kinetics and broth microdilution assays. Effect of ZnO NPs on biofilm formation (both qualitatively and quantitatively) and exopolysaccharide (EPS) production was also determined. Antioxidant potential of green synthesized nanoparticles was detected by DPPH radical scavenging assay. The cytotoxicity studies of nanoparticles were also performed against HeLa cell lines. The results revealed that diameter of zones of inhibition against foodborne pathogens was found to be 16–30 nm, whereas the values of MIC and MBC ranged between 31.25–62.5 μg/ml. Growth kinetics revealed nanoparticles bactericidal potential after 3 hours incubation at 2 × MIC for E. coli while for S. aureus and S. enterica reached after 2 hours of incubation at 2 × MIC, 4 × MIC, and 8 × MIC. 32.5–71.0% inhibition was observed for biofilm formation. Almost 50.6–65.1% (wet weight) and 44.6–57.8% (dry weight) of EPS production was decreased after treatment with sub-inhibitory concentrations of nanoparticles. Radical scavenging potential of nanoparticles increased in a dose dependent manner and value ranged from 19.25 to 73.15%. Whereas cytotoxicity studies revealed non-toxic nature of nanoparticles at the concentrations tested. The present study suggests that green synthesized ZnO NPs can substitute chemical drugs against antibiotic resistant foodborne pathogens.