if=/home/httpd/html/sipbs/images/image_strip_staff.jpg ip=/home/httpd/html/sipbs
  Strathclyde Institute of Pharmacy and Biomedical Sciences

main content

Prof Alastair Florence

MRPharmS
Professor of Pharmaceutical Science

SIBS 601M

alastair.florence@strath.ac.uk

Tel : +44(0)141 548 4877 (Ext. 4877)

Solid-State Research

For current PhD and PDRA opportunities in the group please go to the bottom of the page.

Alastair J. Florence (AJF) is responsible for the Solid-State Research Group (SSRG) within SIPBS. The SSRG specialises in crystallographic investigations of pharmaceuticals (Fig. 1), including aspects of solid-state polymorphism, ranging from crystallisation, to phase transformations, through to crystal structure determination from single-crystal and powder X-ray diffraction data (Fig. 2).

To date, the SSRG has benefited from ca. £2M of investment in state-of-the-art research facilities (Figs. 3 & 4). The dedicated facility includes a suite of three XRPD instruments, a single crystal diffractometer, thermal analysis, automated parallel crystallisation and a range of manual crystallisation techniques, FT-IR, microscopy and dissolution apparatus.

AJF works closely with Dr K. Shankland of Reading University. The collaboration has spawned a wide-ranging program of basic research including: (i) structure determination from synchrotron and laboratory (D8) powder diffraction and (ii) exploiting emerging e-Science technologies including information management systems and distributed computing.

Basic Technology: CPOSS

The SSRG is partiularly active in experimental investigations of the organic solid state under the auspices of the RCUK funded Basic Technology project, co-ordinated by Prof. S. L. Price, University College London, entitled "Control and Prediction of the Organic Solid-State" (www.cposs.org.uk). The group's objectives under the award include the development of polymorph screening approaches for the systematic exploration of parameters critical to the nucleation, crystallisation and transformation of polymorphs.

Recent Initiatives

CPOSS Translation

The CPOSS project has also now secured funding from EPSRC to support translation of the technology started in April 2008.  The activities include collaborative studies exploring the application of the CPOSS experimental and theoretical methodologies, in particular for pharmaceutical APIs. 

If you are interested in discussing translation opportunities please contact AJF. 

Physical Organic Chemistry

We are contributing to a new UK Centre for Physical Organic Chemistry funded via a £4.4M Science and Innovation award(POC Centre). The centre, involving researchers at Strathclyde University (SIPBS and Pure and Applied Chemistry) and Glasgow University (Chemistry) is supported by EPSRC and the Scottish Funding Council. In addition to supporting new staff, the award funds new instrumentation within SIPBS to complement our exisiting facilities including circular dichroism spectrometry; isothermal calorimetry; scanning probe microscopy (AFM/STM) and single crystal diffraction.

SSRG Members

  • Dr Andrea Johnston (PDRA) working on the CPOSS project on implementing experimental crystallisation searches for polymorphs.
  • Jean-Baptiste Arlin (PDRA) working on the CPOSS translation project.
  • Mr Garry Miller (AZ funded PhD) carrying out systematic structural investigations of pharmaceutical salt formation.
  • Mr Ryan Taylor (STFC CMSD/SIPBS studentship) focussing on approaches to structure determination from powder diffraction data.
  • Mr Scott McKellar (CTA/Organon studenthip in Physical organic Chemistry) studying approaches to the crystallization of diffraction quality samples of pharmaceuticals.
  • Ms Rajni Miglani (Commonwealth Scholar) studying experimental approaches to polymorph discovery and control.

Recent Members

  • Dr Julie Bardin studied solvate formation using experimental and molecular modelling approaches. December 2009
  • Dr Philippe Fernandes carried out his PhD and worked as a CPOSS PDRA before joining Onyx Scientific in March 2008.
  • Dr Xuelian Xu, carried out her PhD involving structure determination from powder data and neutron single crystal diffraction studies before joining the academic staff at Ocean University in China in 2006.

cover art for CrystEngComm, 8(10), 746-747, (2006)

Fig. 1 A predicted orthorhombic crystal structure of carbamazepine was identified as isostructural with an experimental structure of form II dihydro-carbamazepine, providing a rationale for synthesising a novel 1:1 solid solution that has carbamazepine in a rare catemeric configuration.

              Structural analysis of a new polymorph of cytenamide

Fig. 2 Cytenamide form I undergoes a solid-state transformation upon heating to form a polycrystalline sample of form II, with the structures exhibiting the same two-dimensional similarity that exists between forms II and III of carbamazepine.


Bruker D8 instruments in the SSRG lab
Fig. 3 Three Bruker-AXS D8 powder diffractometers in the SSRG lab equipped for (left) multi-sample foil transmission analysis (centre) variable temperature capillary data collection for structure determination and phase surveys and (right) a TXS rotating anode system (12kW) with capillary geometry and cryostream system for structure determination and in situ studies of structural transformations.

 

Fig. 4 Automated parallel crystallisation platform in the SSRG lab. Automating searches for polymorphs, solvates, co-crystals and salts enables searches ot be carried out over a finer grid (e.g. larger solvent library) than is practical using traditional manual approcahes. The system enables the automation of basic crystallisation steps with automated solid and liquid dispensing, in-line filtration and controlled cooling or evaporation with or without agitation. The platform is specified to produce ca. 30 samples per day with primary identification carried out using multi-sample XRPD. The automated crystallisation studies are routinely complemented by a wide range of alternative approaches to give a comprehensive view of physical form diversity for compounds under study.

 

 

Current PDRA Positions Available

Current PhD Projects Available

  • Contact: alastair.florence@strath.ac.uk for further details on other available Ph.D. projects within solid-state research. Research areas include: X-ray powder diffraction and single crystal diffraction applied to crystal structure determination, physical characterisation of solids, polymorphism and crystallisation screening, solvate and co-crystal formation, salt selection.

 


Selected Publications

  • Arlin, J.B., Johnston, A., Miller, G.J., Kennedy, A.R., Price S.L.,Florence, A. J. (2010) "A predicted dimer-based polymorph of 10,11-dihydrocarbamazepine (Form IV)"   CrystEngComm DOI: 10.1039/b914365

  • Simon J. L. Billinge, Timur Dykhne, Pavol Juhás, Emil Boin, Ryan Taylor, Alastair J. Florence and Kenneth Shankland (2010) "Characterisation of amorphous and nanocrystalline molecular materials by total scattering"   CrystEngComm DOI: 10.1039

  • Kennedy, A.R., Florence, A.J., McInnes, F.J., Wheate, N.J. (2009) "A chemical preformulation study of a host-guest complex of cucurbit[7]uril and a multinuclear platinum agent for enhanced anticancer drug delivery."   Dalton Transactions 37 7698-7700

  • A. J. Florence (2009) "Approaches to High-Throughput Physical Form Screening and Discovery"   in Polymorphism in Pharmaceutical Solids, 2nd Edition, Ed. H. G. Brittain, Informa Healthcare

  • A.J. Florence, J. Bardin, B. Johnston, N. Shankland and K. Shankland (2009) "Crystal structure determination from powder data: Mogul and CASTEP"   Zeitschrift fur Kristallografie, Suppl. 30 215-220

  • Fabbiani, F. P. A., Dittrich, B., Florence, A. J., Gelbrich, T., Hursthouse, M. B., Kuhs, W. F., Shankland, N., Sowa, H., (2009) "Crystal structures with a challenge: high-pressure crystallisation of ciprofloxacin sodium salts and their recovery to ambient pressure"   CrystEngComm 11 1396-1406

  • Thomas L.H., Florence A.J., Wilson C.C. (2009) "Hydrogen atom behaviour imaged in a short intramolecular hydrogen bond using the combined approach of X-ray and neutron diffraction "   New Journal of Chemistry 33 2486-2490

  • K. Shankland, T. A. N. Griffin, J. van de Streek, J. C. Cole, N. Shankland, A. J. Florence and W. I. F. David (2009) "Large-scale distributed computing for accelerated structure solution"   Zeitschrift fur Kristallografie, Suppl. 30 227-232

  • A. J. Florence (2009) "The Solid State"   in Modern Pharmaceutics, Volume 1, Basic Principles and Systems, Informa Healthcare, New York

  • Florence, A. J., Shankland, K., Gelbrich, T., Hursthouse, M.B., Shankland, N., Johnston, A., Fernandes, P., Leech, C.K. (2008) "A catemer-to-dimer structural transformation in cyheptamide"   CrystEngComm 10 26-28

  • Fernandes, P., Shankland, K., David, W.I.F., Markvardsen, A.J., Florence, A. J., Shankland, N., Leech, C. K. (2008) "A differential thermal expansion approach to crystal structure determination from powder diffraction data "   Journal of Applied Crystallography 41 1089-1094

  • Barnett, S. A., Johnston, A., Florence, A. J., Price, S. L. and Tocher, D. A. (2008) "A systematic experimental and theoretical study of the crystalline state of six chloronitrobenzenes"   Crystal Growth and Design 8 24-36

  • Johnston, A., Johnston, B.F., Kennedy, A.R., Florence, A.J. (2008) "Targeted crystallisation of novel carbamazepine solvates based on a retrospective Random Forest classification. "   CrystEngComm 10 23-25

  • Florence, A. J., Bedford, C. T., Fabbiani, F. P. A., Shankland, K., Gelbrich, T., Hursthouse, M. B., Shankland, N., Johnston A. and Fernandes P. (2008) "Two-dimensional similarity between forms I and II of cytenamide, a carbamazepine analogue"   CrystEngComm 10 DOI: 10.1039

  • Leech, C. K., Florence, A.J., Shankland, K., Shankland N. and Johnston, A. (2007) "10,11-dihydrocarbamazepine (form III)"   Acta Cryst. E63 o205-o206

  • Fabbiani, F., Leech, C. K., Shankland, K., Johnston, A, Fernandes, P., Florence, A. J. & Shankland, N. (2007) "Hirshfield surface analysis of two bendroflumethiazide solvates"   Acta Cryst. C63 o659-663

  • Hawxwell, S. M., Mínguez Espallargas, G., Bradshaw, D., Rosseinsky, M. J., Prior, T. J., Florence, T. J., van de Streek, J. and Brammer, L. (2007) "Ligand Flexibility and Framework Rearrangement in a New Family of Porous Metal-Organic Frameworks"   Chem. Commun. 1532-1534

  • Fernandes, P., Florence, A.J., Shankland, K., Karamertzanis, P. G., Hulme A. T. and Anandamanoharan, P. (2007) "Powder study of (R)-1-phenylethylammonium (R)-2-phenylbutyrate form 3"   Acta Cryst. E63 o202-o204

  • Fernandes, P., Shankland, K., Florence, A.J., Shankland, N., & Johnston. A. (2007) "Solving molecular crystal structures from X-ray powder diffraction data: the challenges posed by gamma-carbamazepine and chlorothiazide N,N,-dimethylformamide (1/2) solvate"   J. Pharm. Sci. 96(5) 1192-1202

  • Karamertzanis, P. G., Hulme, A. T., Anandamanoharan, P. R., Fernandes, P., Cains, P. W., Vickers, M., Tocher, D. A., Florence, A. J. and Price, S. L. (2007) "The crystal packing and relative stabilities of diastereomeric salt pairs: The case of 1-phenylethylammonium 2-phenylacetate derivatives"   J. Phys. Chem. B 111(19) 5326-5336

  • Hulme, A.T., Johnston, A., Florence, A.J., Fernandes, P., Shankland, K., Bedford, C.T., Welch, G.W.A., Sadiq, G., Haynes, D., Motherwell, W.D.S., Tocher, D.A., Price, S.L., (2007) "The Search for a Predicted Hydrogen Bonding Motif – A Multidisciplinary Investigation into the Polymorphism of 3-Azabicyclo[3.3.1]nonane-2,4-dione"   J. Am. Chem. Soc. 129(12) 3649-3657

  • Florence, A.J., Leech, C.K., Shankland, N., Shankland K. and Johnston, A. (2006) " Control and prediction of packing motifs: a rare occurrence of carbamazepine in a catemeric configuration"   CrystEngComm 8(10) 746-747

  • Florence, A.J., Johnston, A., Price, S.L., Nowell, H., Kennedy, A.R., Shankland, N. (2006) "An automated parallel crystallisation search for predicted crystal structures and packing motifs of carbamazepine"   J. Pharm. Sci. 95(9) 1918–1930

  • Florence, A.J., Johnston, A., Fernandes, P., Shankland N. and Shankland, K. (2006) "An Automated Platform for Parallel Crystallisation of Small Organic Molecules"   J. Appl. Cryst. 39(6) 922-924

  • Espallargas, G. M., Brammer, L., van de Streek, J., Shankland, K., Florence, A. J., and Adams, H. (2006) "Reversible extrusion and uptake of HCl molecules by crystalline solids involving coordination bond cleavage and formation"   J. Am. Chem. Soc. 128(30) 9584-9585

  • Wilson, C.C., Xu, X.L., Florence, A. J. and Shankland, N. (2006) "Temperature dependence of proton transfer in 4-chlorobenzoic acid"   New J. Chem. 30(7) 979-981

  • Lewis, G., Steele, G., McBride, L., Florence, A.J., Shankland, N., Kennedy, A.R., Shankland, K. (2005) "Hydrophobic vs. hydrophilic: ionic competition in remacemide salt structures"   Crystal Growth and Design 5 427-438

  • Florence, A.J., Shankland, N., Shankland, K., David, W.I.F., Cox, P.J., Evans, J., Kennedy, A.R., Pidcock, E., Frampton, C., Johnston, A. and Xu, X (2005) "Solving Molecular Crystal Structures from Laboratory X-ray Powder Diffraction Data with DASH: the State of the Art and Challenges."   J. Appl. Cryst. 38 249-259

page last updated: 17/12/2009