An assessment of cross-contamination issues in the context of chemical and pharmaceutical processes using a continuous oscillatory baffled reactor

Abstract

Past research in oscillatory baffled reactors has shown that there are significant technological and business advantages in using such reactor technology in fine chemical and pharmaceutical industries: shorter reaction times, fewer by-products, uniform product quality and higher yields, while at the same time with a significant saving in space, capital and running costs. This project focused on the robustness and adaptability of the continuous oscillatory baffled reactor (COBR) for a large spectrum of chemical reactions that are performed in very different fields of industry: from cosmetics and fine chemicals to pharmaceutical products. In particular, the emphasis was on cross contamination issues which may occur when different reactions are performed in a tandem fashion in this reactor. The experimental results indicate that the COBR is well suited to a broad spectrum of chemical reactions, as well as for crystallization operations. During the continuous production of a fine chemical and two active pharmaceutical ingredients in tandem the conditions inside the reactor remained stable and were easily controlled. The minimal amounts of contaminants present and the high quality of the products obtained are a testament to the consistent operation and robust nature of the COBR. The three production phases were interspersed with a well-defined cleaning procedure. The established cleaning protocol is simple, efficient and fast, while the amount of waste generated is minimized. The cleaning kinetics is of first order, which is consistent with previous work. The results reported in this thesis show that the COBR, which incorporates quality-by-design principles, is a suitable alternative to current mixing technologies and can be readily assimilated into a variety of fine chemical and pharmaceutical manufacturing processes.