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Dr Nicholas Blagden DPhil, BSc (Hons)
Reader in Solid State Pharmaceutics
  • Telephone: +44 (0) 1274 234765
  • Email: n.blagden@bradford.ac.uk

Dr Nicholas Blagden is a Reader in Solid State Pharmaceutics at the School of Pharmacy, University of Bradford, UK. He has a joint honours degree in chemistry and physics, (1984-1987), and a DPhil in chemical physics (1992) under the supervision of Professor Kenneth Seddon. Before taking up his current post he worked as the Crystallisation Specialist for Avecia (2000-2001) and has undertaken postdoctoral work in crystal engineering at UMIST with Professor Roger Davey (1995-2000) and bio-mineralization with Professor Brigid Heywood (1993-1995).

Summary and Relevance of Research: the finding of Dr Blagden’s research has contributed to new knowledge in the fields of crystal engineering and analytical techniques for the in situ study of crystallisation. This has led to a notable first insight into the molecular control of the crystallisation process for organic solid materials. These activities contribute to the understanding of the issues of polymorphism, salts and co-crystals in drug development process and in materials chemistry, both academically and industrially. His research has contributed a number of notable firsts in the area of polymorph selection and pre-nucleation (1,2). At Bradford, he is continuing work on directed epitaxy(5), nano drug particle synthesis using micro-fluidic reactors, and continues work on the crystal engineering of active pharmaceutical ingredients(8-10).

Research Theme Synopsis
Dr Blagden has specialized in the relationship between molecular self-association observed in solution with the molecular assembly of the solid phase, and the impact this has on the physico-chemical or biophysical behaviour of materials. Within the molecular solids area, his research has focused on the isolation of polymorphs through solvent selection and designer additives(1). His contribution to this area of research is to place the influence of polymorph transformation by solvents and additives on a molecular recognition basis(2). This approach employs both the use of predicted crystal structures and the application of surface stereochemistry using graph sets. This approach was used successfully in the design of a glue to induce twinning in saccharin, where twinning was treated as the simplest case of epitaxy(3) and to induce crystallographic led aggregation of preformed crystals (4,5). This work has contributed at an international level to applying the lock and key concepts of crystal growth to the screening and stabilization of molecular solid polymorphs, chiral salts and co-crystals (6-10). Dr Blagden has published two book chapters, thirty six papers, four reviews, holds two patents, and has given 32 invited lectures to both academic and industrial conferences. He has chaired sessions at the 2003 congress of the International Union of Crystallography on insitu monitoring of crystallization, and the 2006 BCA spring meeting on crystal engineering and is a consultant for Avecia and Syngenta.

See specific research highlight links for further detail of the research within the group.

  • Polymorphism
  • Crystal Engineering
  • Analytical Techniques


    Polymorph Selection

    Within the field of polymorph selection three contributions are regarded as worthy of particular mention, all of which have resulted from active research and high impact outputs in the field. Firstly, growth inhibition of one polymorph over another defined a route to stabilising a meta-stable phase. The contribution here was to define how additives or solvents could be used to disrupt the growth of stable forms on a molecular self-assembly basis. The programmed design of inhibitors led to the first defined application of graph set analysis of hydrogen bonding to polymorphic selection. This mapping was used to define the similarities and differences in the molecular assembly of polymorphs, which enabled definition of the critical interaction at a molecular level for stabilising one polymorph over another by a solvent or additive.
    Secondly, a contribution was made in defining a link between self-associations of solute molecules in solution prior to nucleation, which was then related to the appearance of one particular polymorph over another. Research in this area pioneered the use of UV, Raman, Synchroton X-ray diffraction and NMR to this problem. Studies of links between molecular aggregates in solution and those in solid phase are continuing with the application of a XRD-Raman approach. The hybrid approach has been adopted as a means of providing simultaneous structural and chemical detail of the crystallisation process.
    Thirdly, new understanding highlighted the possibility of using simulated structures and applying the learning from the previously stated areas to target a particular packing family from a crystal packing simulation.


    Crystal Engineering

    The basis of this work lies in being able to use the crystallography of component materials to promote the agglomeration or composite assembly of molecular crystals. The major achievement in this area was in designing an effective additive to direct twinning. This understanding led to further research and design of our new ‘capper additives’ concept to promote the epitaxial growth of a molecular solid. Further efforts both experimentally and computationally based have led directly to establishing a molecular basis of directed epitaxy. Within this area the suitable modelling to identify the correct epitaxial registry between the boundary of one phase and another has been instrumental.
    These ideas are also being employed in forming nanoparticles of molecular solids, and refined further to enable the generation of composite crystal at both the molecular level and within colloidal domains.
    These activities are unique worldwide, with the applicant taking a distinctive and unique approach to the area of crystal engineering by integrating this area with a crystal growth perspective. This effort includes co-crystallisation using both supra molecular libraries and pharmaceutical ingredients. My new approach goes beyond the traditional crystallographic approaches used to exploit elements of my previous polymorph selection work in this area of crystal engineering.


    Analytical Techniques

    A major challenge within this area of research has been in developing the capacity to record polymorph transformation in real-time and, in one specific case, resolve the issue of the polymorphism of benzamide. This has led to an innovative approach based on a clarifying crystalliser to deliver a plume of solid to an x-ray beam, where the diffraction from the solid is resolved from that of the solution. This approach will help to develop a new way to screen polymorphs and co-crystal from a kinetic viewpoint.

    Selected Publications
    1. N.Blagden, R.J.Davey, Polymorph selection: challenges for the future, Cryst. Growth & Design, (2003), 3, 873
    2. R.J.Davey, N.Blagden, A.H.Righini, E.S.Ferrari, Crystal polymorphism as probe for molecular self-assembly during nucleation from solution: the case of 2,6 dihydroxybenzoic acid, J. Phys. Chem., (2002), 106, 1954
    3. R.J.Davey, L.Williams-Seton, H.F.Lieberman, N.Blagden, Stabilising a solid-solid interface with a molecular scale adhesive, Nature, (1999), 402, 797.
    4. N.Blagden, B.R.Heywood, Crystal assembly using high affinity ligands, Cryst. Growth & Design, (2003), 3, 167.
    5. C.C.Seaton, N.Blagden, Directed Epitaxy-a computational model, ACA Trans., (2004), 39. 90.
    6. R.Davey, R.Moguail, N.Blagden, Application of crystallisation inhibitors to chiral separations. Design of additives to discriminate between the racemic compound and the pure enantiomer of mandelic acid, Cryst. Growth & Design, (2007), 7(2), 218.
    7. L.L.DeMatos, A.C.Williams, S.W.Boot, C.R.Petts, D.J. Taylor, N.Blagden, Solvent influences on metastable polymorph lifetimes: real-time interconversion using energy dispersive X-ray diffractometry, J. Pharm. Sci., (2007), 96(5), 1069.
    8. A.Parkin, C.C.Seaton, N.Blagden, C.C. Wilson, Designing hydrogen bonds with temperature-dependant proton disorder: the effect of crystal environment, Cryst. Growth & Design, (2007), 7(3), 531.
    9. N.Blagden, W.L.Cross, R.J.Davey, M.Broderick, G.Pritchard, R.J.Roberts, R.C.Rowe, Can crystal structure prediction be used as part of an integrated strategy for ensuring maximum diversity of isolated crystal forms? The case of 2-amino-4-nitrophenol, Phys. Chem. Chem. Phys. (2001), 3, 3819.
    10. N.Blagden, M.Song, R.J.Davey, Linda Seton, C.C. Seaton, Ordered aggregation of benzamide crystal induced using a motif capper additive, Cryst. Growth & Design (2005), 5(2),467.

    Invited presentations:

    •British Association Pharmaceutics (2006)London /UK. Epitaxy/ co-crystals

    •British Association Crystal Growth (2006)Glasgow/UK. Co-crystals