Control and optimization of continuous chromatographic separation processes

The modern trend of pharmaceutical technology has been greatly shifted towards single or pure enantiomeric drugs due to strict regulations imposed by drug approval authorities in order to obtain higher drug efficiency and to alleviate undesirable side effects. Enantiopure compounds can be accessed either by organic synthesis or by resolution techniques. Recently, chromatographic separation has become the preferred method for its cost effectiveness, ease of operation, and flexibility as it employs variety of processing materials and methods supported by rich theoretical background. Simulated moving bed (SMB) has been extensively used for the separation of chemicals in the past 50 years, though its application to enantioseparation is relatively new. Supported by the benefits of counter-current mode of operation, SMB has become the method of choice for large-scale operations. However, SMB is a complex process both in terms of design and operation. There have been numerous efforts to emulate SMB by simpler processes. Many of them are based on using a single column with a recycle stream. In this work, we proposed an improved single-column chromatographic (ISCC) separation process. The term `improved' refers to both conceptual and physical modifications. We proposed a novel fraction collection scheme and allowed overlapped peaks from adjacent cycles. We also modified the fraction collection mechanism in order to facilitate online monitoring. Another advantage of the ISCC process is its large degree of freedom as injection volume, cycle time, desorbent flow rate, feed concentration and fraction-collection intervals can all be decision variables in this process. Every continuous process needs some sort of feedback from the process for quality control and monitoring. The chromatographic separation processes are usually monitored via low-frequency devices such as analytical high-performance liquid chromatography (HPLC) systems. Alternatively, innovative approaches have been taken to improve the sampling rate using combination of various detectors, peak deconvolution, etc. The design of an efficient online monitoring system is still an open problem. In this work, we proposed an online monitoring system, which comprises of two parallel HPLC units with customized peripherals in order to improve the accuracy and sampling rate. The proposed device can be readily coupled to the ISCC process. It is also less expensive compared to the similar commercial units. Minimizing operation costs and maximizing productivity are necessary for a profitable operation. They are typically complex functions of process inputs, and the operation might be limited by certain constraints as well. Similarly, optimization is not straightforward for the ISCC process as there are several variables contributing to a multi-dimensional solution space. On the other hand, process outputs have opposing effects on the profitability of the process. As a result, there may not be a single dominating solution as the best operating point.DOCTOR OF PHILOSOPHY (SCBE

Optimization of an improved single-column chromatographic process for the separation of enantiomers

This work addresses optimization of an improved single-column chromatographic (ISCC) process for the separation of guaifenesin enantiomers. Conventional feed injection and fraction collection systems have been replaced with customized components facilitating simultaneous separation and online monitoring with the ultimate objective of application of an optimizing controller. Injection volume, cycle time, desorbent flow rate, feed concentration, and three cut intervals are considered as decision variables. A multi-objective optimization technique based on genetic algorithm (GA) is adopted to achieve maximum productivity and minimum desorbent requirement in the region constrained by product specifications and hardware limitations. The optimization results along with the contribution of decision variables are discussed using Pareto fronts that identify non-dominated solutions. Optimization results of a similar simulated moving bed process have also been included to facilitate comparison with a continuous chromatographic process

Distribution and health risk assessment of heavy metals in soil surrounding a lead and zinc smelting plant in Zanjan, Iran

<p>One of the problematic issues in soil pollution studies is heavy metal particles which are produced by mines and smelting units and spread through wind action and/or runoff. Pollution and health risk assessment of cadmium, lead, zinc, copper, and nickel in soil around the lead and zinc smelting factory was carried out in Zanjan City, Iran. Contamination factor (Cf), pollution load index (PLI), geoaccumulation index (Igeo), hazard quotient (HQ), hazard index (HI), and carcinogenic risk were pollution and human health risk assessment metrics in this study. Based on the Iranian soil guideline value, soil samples in the studied areas were contaminated the least by copper and nickel and the most by cadmium. PLI results showed that soils near the production line were heavily or extremely heavily polluted. The results of Cf and Igeo showed that lead and zinc were the most important contaminants. Health risk assessment indicated that lead and cadmium in soil were the main contaminants, which pose both carcinogenic and non-carcinogenic risks to human health; carcinogenic risk levels were unacceptably high (above 1 × 10⁻⁴). It can be concluded that mining and smelting activities degrade soil quality in this region and the soil pollution might be extended to farming areas.</p