Preparative Chromatography for Production

From a very simple process like sieving to a more complex one such as petrol fractionation by distillation, separations techniques are an essential tool for chemists and chemical engineers to achieve purity. However, every unit operation must be understood thoroughly so it can be used to its fullest potential. Once the science behind the process is understood, then improvements can be imagined, designed, and implemented. Unfortunately, some techniques are rarely used despite their proven performance due to a fundamental lack of understanding. Preparative chromatography is one of these underappreciated techniques. Despite significant improvements in the technology over several decades, this powerful unit operation is still underutilized especially in the pharmaceutical industry. This article provides an overview of preparative chromatography as a unit operation and show how this process, when optimized, can provide a significant cost improvement to a chemical process. The focus is mostly on the use of preparative chromatography, batch and continuous, for small molecule active pharmaceutical ingredients (APIs), however the technique is successfully used in a vast range of applications from the purification of molasses at very large scale to the petroleum industry. In a first part, a short overview of the history of the technique is presented. Focus is placed on the understanding of the process resulting in very powerful computer modeling tools that can be used to compare the process to other techniques. Finally, the development of the process for an API from the early clinical stage to the commercial manufacturing is discussed and the implantation at industrial scale is featured. It is assumed that the reader is familiar with analytical chromatography and basic chromatographic concepts such as retention time, selectivity, resolution, and column efficiency. If the reader is not familiar with these notions we recommend references [1–3].