Abstract

Plant alkaloids are natural secondary metabolites that have attracted great interest in the development of drugs for therapeutic applications due to their diverse bioactivities. For the pharmaceutical, cosmetic, and food industries, the development of alkaloid-based formulations is a long path that requires several steps (extraction, separation, isolation, and encapsulation) and diverse techniques of analysis (quantitative and qualitative). These conventional methodologies are not sustainable for the environment, especially at the pilot scale. In this context, the development and application of sustainable green chemistry throughout the entire process can be successfully achieved with supercritical fluid (SF) technology. In this review, we provide a comprehensive and critical overview of the recent applications of SF processes in the study of alkaloids and their future perspectives. A special focus on the development and applications of the on-line coupling of SF-extraction (SFE) with SF-chromatography (SFC) is given. This coupling permits the use of a completely environmentally friendly process of extraction and separation/isolation in semi-preparative and preparative modes. The stabilization of alkaloids through encapsulation and micronization permits the application of SF processes throughout the whole workflow, from plant matrix extraction to stable product development. In addition, the global alkaloid market and SFE economic feasibility at an industrial scale are discussed. Overall, SF technology is a versatile and eco-friendly alternative for the analysis and production of alkaloids that requires technical and analytical development according to the matrix and the chemical characteristics of the alkaloid.