Scalable Technology for the Extraction of Pharmaceutics: Outcomes from a 3 year collaborative industry/academia research programme

Abstract

This paper reports on some of the key outcomes of a 3 year £1.5m Technology Strategy Board (TSB) funded research programme to develop a small footprint, versatile, counter-current chromatography purification technology and methodology which can be operated at a range of scales in both batch and continuous modes and that can be inserted into existing process plant and systems. Our consortium, integrates technology providers (Dynamic Extractions) and the scientific development team (Brunel) with end user needs (GSK & Pfizer), addressing major production challenges aimed at providing flexible, low capital platform technology driving substantial cost efficiency in both drug development and drug manufacturing processes. The aims of the Technology Strategy Board's high value manufacturing programme are described and how the academic/industry community were challenged to instigate step changes in the manufacturing of high value pharmaceuticals. This paper focusses on one of the themes of the TSB research programme, "Generate a Comprehensive Applications Portfolio". It outlines 15 applications from this portfolio that can be published in the public domain and gives four detailed case studies illustrating the range of application of the technology on the separation of (1) isomers, (2) polar compounds, (3) crude mixtures and (4) on the removal of impurities. Two of these case studies that were scaled up demonstrate between 10 and 20% lower solvent usage and were projected to have significant cost savings compared to conventional solid phase silica gel chromatography at procss scale demonstrating that the latest high performance countercurrent chromatography technology is a competitive platform technolgy for the pharmaceutical industry.

Methodology for optimally sized centrifugal partition chromatography columns

“…As highlighted by Sutherland et al [2], counter current separations technologies (including CCC and CPC apparatuses) present some advantages compared to conventional separations techniques. The first advantage of counter current technologies is that they provide high productivities (1 kg/day at a laboratory scale).…”

The SOLUTIONS project: Challenges and responses for present and future emerging pollutants in land and water resources management

“…SOLUTIONS will address the challenge of low water EQS and will design an optimised work flow for low detection limits using passive sampling (Lohmann et al, 2012;Smedes et al, 2013), large volume in situ solid phase extraction (LV-SPE, (Schulze et al, 2012)), on-line size exclusion devices, and dynamic extraction applying High Performance Counter Current Chromatography (HPCCC) (Sutherland et al, 2013). …”

Purification of Active Myrosinase from Plants by Aqueous Two‐Phase Counter‐Current Chromatography

“…It permits enhanced mixing of the ATPS in a manner similar to the much larger multilayered toroidal coils that have been pioneered for use with ATPS on commercially available and highly scalable J‐type CCC configurations (Guan et al , ; Sutherland, ; Sutherland et al , ). This work and that of others suggests that scale‐up of this method should be facile and predictable (Fisher et al, ; Guan et al, ; Ito et al, ; Wood et al, ; Sutherland et al , ), and that the use of CCCs with greater column capacity will result in a concomitant increase in the yield of catalytically active myrosinase, if they can be adapted to this or other tubing design that permits greater retention of ATPS phases. Thus, based only upon first principles, 80 g of dried moringa leaves might be used to charge one of the largest available CCCs today (18 L column capacity), for a per‐run yield of about 740 Units in a gram.…”