Objective The rationaleOver half of marketed drugs are chiral and exist at least in two symmetrical enantiomer forms. In many cases one form is therapeutically useful whilst the other may be less active, inactive or even toxic. Thus enantiomeric composition, purity and stability are major regulatory requirements for such compounds. However difficulties in separation of chiral forms for synthetic drugs frequently make pharmaceutical development of a single enantiomer economically unfeasible. Whilst crystallization is the simplest and most efficient method for chiral separation (resolution) of enantiomers or their diastereomeric salts, complex kinetics of this process make the development of crystallization methods inefficient and time-consuming. As a result, control over chiral purity, physical form and crystallinity of products remains inadequate. Thus, different batches of the same product can perform or behave unpredictably and impair product development or manufacture.The objectivesThe project aims to investigate the fundamental aspects of enantiomeric separation kinetics and impurity adsorption during crystallization and develop enhanced technological schemes for batch and continuous solution crystallization methods. In addition, novel technological approaches to resolve chiral mixtures using supercritical fluids (SCF) will be investigated, giving the benefit of a single-step and recyclable process engineering. A concentrated analytical effort will be made to optimise these processes in terms of purity, reproducibility and consistency of the products.The programmeThe project incorporates three principle research areas: development of solution crystallization techniques, proof of concept research into SCF crystallization and analytical studies of the resolved drug materials. Both experimental and theoretical approaches will be applied to investigate the crystallization kinetics of selected chiral drugs and impurity molecules. The final project phase involves industrial evaluation and scale-up.The partnersThe partners provide expertise in the following areas key to the success of the programme: pharmaceutical technology and SCF technology (University of Bradford, UK), industrial validation and scale-up (Bradford Particle Design plc, UK), pharmaceutical and analytical organic chemistry (University of Pavia, Italy), fundamental crystallization science and solution physical chemistry (Institute of Crystallography, Russia), crystallization technology (Institute of Technical Acoustics, Belarus) and analytical pharmaceutical chemistry (Republican Inspection - Analytical Laboratory, Belarus). All these research groups are well established and equipped to extend theoretical knowledge and research new experimental techniques in the area of chiral separations with a view to exploit these developments directly and promptly for practical applications.The expected resultsThe main expected outputs include: a comprehensive mechanistic description of crystallization in solution in relationship to the properties of crystals obtained; optimisation criteria for these processes which allows separation efficiency above 95%; proof of concepts for direct and diastereomeric resolution of chiral drugs using SCF; enhancement of consistency, reproducibility and particulate properties of materials produced using SCF; scale up criteria for solvent based and SCF crystallization processes. Programme(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Topic(s) 3 - Chemistry OPEN - OPEN Call Call for proposal Data not available Funding Scheme Data not available Coordinator University of Bradford EU contribution No data Address Richmond Road BD7 1DP Bradford United Kingdom See on map Total cost No data Participants (5) Sort alphabetically Sort by EU Contribution Expand all Collapse all Bradford Particle Design plc United Kingdom EU contribution No data Address 69 Campus Road, Listerhills Science Park BD7 1HR Bradford See on map Total cost No data National Academy of Sciences of Belarus Belarus EU contribution No data Address Ludnicov prospect, 13 210717 Vitebsk See on map Total cost No data Republican Inspection-Analytical Laboratory Belarus EU contribution No data Address D.Marcinkevich Street, Corp.1, No.4 220092 Minsk See on map Total cost No data Russian Academy of Sciences Russia EU contribution No data Address Leninski prospekt 59 117333 Moscow See on map Total cost No data University of Pavia Italy EU contribution No data Address Viale Taramelli, 12 27100 Pavia See on map Total cost No data
