This work is part of the project produced for Alzeim Ltd under the KnowledgeTransfer Programme between the University of Manchester and Alzeim Ltd.Alzeim's intention is to become a sustainable supplier of Galanthamine API, for use inAlzheimer's Disease treatments. The synthetic sources of Galanthamine are costly anddifficult to make so Alzeim has built upon its discovery of economic levels of thecompound in daffodils grown in Wales to develop an agricultural growing method forfield production. This project suggests the modification of a batch laboratory process intoa continuous processing unit.The purpose of this work was to implement Liquid-Liquid extraction usingfermented daffodil juice as the Galanthamine source. A model of a liquid-liquid RotatingDisc Contactor is postulated with inner diameter of 100mm and compartment height of1.2m. Additional modification was made by inserting a sieve disc between the existingplain discs. The experimental study of possible approaches to Galanthamine extraction ina continuous process were run in a counter-current scheme with solvent being thedispersed phase. Operating variables like pH , solvent type, rotation speed and flow rateswere investigated and assessed using the mass transfer efficiency as measured by HPLCanalysis of samples and phase separation. Due to of complexity of the raw material(consisting of many other alkaloids, proteins, sugars, etc) two extraction steps wereproposed. Firstly purification of the juice by removal of other alkaloids from the feed juiceand secondly the Galanthamine transfer into solvent phase for its further crystallization.From initial test tube experiments the pH for the two steps was determined to bebetween 6-7 for the purification step and 9 for the extraction step. Of the two solventsconsidered for purification, Solvent-B was more selective, however it was too soluble inthe aqueous phase making separation problems at the second step. Consequently,Solvent-A was proposed for the first part of the process, with the implementation of abackwash for Galanthamine recovery. Solvent-D was chosen for the second step as itmost closely fulfilled the objectives of this step.Full scale column trials were used to determine the optimum flow rate of 45L/hfor the continuous phase at the both steps and the phase ratio for first and second stepas 0.5 and 0.33 respectively. Trials showed that the average extraction yield is 70%,depending on the initial concentration of Galanthamine in the raw juice. These trials alsorevealed the problem of emulsion generation during the process in the rotating disccolumns. This led to proposal of carry out better juice pre-treatment using coagulant toremove solids as well as additional column modifications.It has been shown that with chosen pH range, flow conditions and reducedemulsion problem the two-step Galanthamine extraction process can be runcontinuously. However, to achieve the optimum mass transfer greater column height isrequired. Also further searching of more selective solvents are required to increase theefficiency of the purification step and obtain higher purity of product at the end ofprocess.
|Date of Award
|31 Dec 2012
- The University of Manchester
|Severino Pandiella (Supervisor)
- Rotating Disc Column