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Professor Geoff Smith

Job: Professor of Pharmaceutical Process Analytical Technology

Faculty: Health and Life Sciences

School/department: Leicester School of Pharmacy

Research group(s): Pharmaceutical Technologies

Address: Â鶹ƵµÀ, The Gateway, Leicester, LE1 9BH.

T: +44 (0)116 250 6298

E: gsmith02@dmu.ac.uk

W: www.dmu.ac.uk/pharmaceutical

Social Media:

 

Personal profile

Geoff Smith graduated in Pharmacy from the University of Bath in 1985 and obtained his PhD from the University of Brighton in 1991 based on a study of the mechanisms of action of cryoprotectants. It was then that he developed a keen interest in the dielectric properties of materials.

He joined Â鶹ƵµÀ in 1993 and went on to develop a number of lines of research based around broad band dielectric measurements. In recent years these studies are focussed increasingly on PAT applications in process development and manufacturing controls for the pharmaceutical industry. His research group is now working on a number of pharmaceutical applications for impedance, dielectric and terahertz spectroscopy alongside optical techniques such as laser speckle and optical flow. These techniques cover an extremely wide range of frequencies thereby enabling the direct analysis of material properties over a wide range of scales from the macroscopic to the molecular.

He was responsible for the development of through-vial impedance spectroscopy (LyoDEA) as a PAT tool for monitoring phase behaviour (ice formation and eutectics), temperatures, and drying profiles and end points, in collaboration with GEA Pharma Systems and AstraZeneca (Funded by the Technology Strategy Board).

More recently his pharmaceutical research focus has extended to investigations into the use of electrostatic noise measurements and optical imaging for applications in roller compaction, powder flow and tablet defect analysis, with the aim of improving understanding and control of tablet production methods.

From 2007 he began to re-structure the Pharmaceutical Technologies group, by recruiting staff from various backgrounds, including chemists, physicists, chemical engineers and process control specialists in order to diversify the research base of the group and to re-focus efforts on current pharmaceutical industry challenges in product design and manufacturing. By 2010 he had instigated Â鶹ƵµÀ's Pharmaceutical Quality by Design programme, with a wide range of industrial practitioners providing webinars on elements of quality by design.

 

Research group affiliations

Pharmaceutical Technologies 

Publications and outputs


  • dc.title: Dielectric spectroscopy of the low-losses sugar lyophilises: IV. Comparative study of four disaccharides at different moisture contents and temperatures dc.contributor.author: Ermolina, Irina; Smith, Geoff dc.description.abstract: The purpose of this article is to study the effect of moisture content on the molecular dynamics of freeze-dried disaccharide excipients, in the context of understanding the instability of a pharmaceutical product. Four di saccharides were measured by broad band dielectric spectroscopy, over a wide temperature range (− 140 to +80 â—¦C) with increasing moisture content from 1 to 7.5%. The two observed sub-Tg relaxation processes (β and γ) were affected by the moisture content, with a dramatic change in relaxation time of the β-process, but only a moderate effect on the γ-process. A suggestion of the likely arrangement of dipoles, and intra-molecular mobility, was performed in the framework of the free-space theory and based primarily on the analysis of the relaxation times, activation energies and Frohlich parameters. This analysis allows for some speculation concerning the disaccharide moisture buffering in freeze-dried formulations. dc.description: open access article

  • dc.title: Observations on the Changing Shape of the Ice Mass and the Determination of the Sublimation End Point in Freeze-Drying: An Application for Through-Vial Impedance Spectroscopy (TVIS) dc.contributor.author: Pandya, Bhaskar; Smith, Geoff; Ermolina, Irina; Polygalov, Evgeny dc.description.abstract: Models for ice sublimation from a freeze-drying vial rely on the assumption of a planar ice interface up to ~25% loss of ice mass (which is difficult to qualify) whereas single-vial determinations of the sublimation endpoint (by temperature sensors) are based on the point when the observed temperature reaches a plateau, which cannot differentiate between sublimation and desorption-drying. In this work, the real part capacitance of TVIS vial(s) containing frozen water (during sublimation drying) was measured at 100 kHz. This parameter C′(100kHz) was shown to be highly sensitive to the shape and volume of the ice mass and is therefore a useful parameter for monitoring ice sublimation. By placing a digital camera in front of an isolated TVIS vial containing ice, it was possible to relate the changes in the shape of the ice mass with the changes in the trajectory of the time profile of C′(100kHz) and determine the point of deviation from a planar ice interface and ultimately determine the point when the last vestiges of ice disappear. Thereafter, the same characteristics of the C′(100kHz) time-profile were identified for those TVIS vials located out of sight of the camera in a separate full-shelf lyo study, thereby obviating the need for photographic examination. dc.description: open access article

  • dc.title: Lyosenseâ„¢: A method for controlling and/or monitoring process parameters of the lyophilization process. dc.contributor.author: Smith, Geoff; Polygalov, E.; Page, T.

  • dc.title: Application of Through Vial Impedance Spectroscopy for Lyophilization Process Development dc.contributor.author: Pandya, Bhaskar; Smith, Geoff; Polygalov, E.; Ermolina, I.

  • dc.title: New Impedance Based Methodologies to Determine the Vial Heat Transfer Coefficient and the Endpoint of Primary Drying dc.contributor.author: Pandya, Bhaskar; Smith, Geoff; Polygalov, E.; Ermolina, I.

  • dc.title: Multiplexing Single-Vial Process Analytical Technologies dc.contributor.author: Smith, Geoff

  • dc.title: Application of through vial impedance spectroscopy to different containers dc.contributor.author: Vadesa, A.; Smith, Geoff; Polygalov, E.; Horley, Neill; Dalby, Paul

  • dc.title: Prediction of the Collapse of Freeze-Dried Lactose Solution using Through Vial Impedance Spectroscopy (TVIS) dc.contributor.author: Jeeraruangrattana, Y.; Polygalov, E.; Ermolina, I.; Smith, Geoff dc.description.abstract: The aim of this work is to evaluate the application of TVIS system for the prediction of micro-collapse during a freeze-drying cycle. The electrical impedance of a 5%w/v lactose solution contained within a modified glass freeze-drying vial was measured over the frequency range of 10 Hz to 1 MHz during the entire freeze-drying process. A significant decrease in CʺPEAK at the point of micro-collapse (as confirmed by SEM) highlights the potential for using TVIS for monitoring microscopic changes in the product resistance to vapour flow associated with the phenomenon of micro-collapse. This study also demonstrated a good correlation between TVIS data (Log FPEAK) and temperature of the frozen solution during the annealing stage of the cycle. By using a temperature calibration from the annealing stage it was possible to predict the onset of collapse and thereby demonstrate the potential for TVIS to be used as a process control tool that would allow the cycle to be driven at the highest achievable temperature whilst avoiding collapse.

  • dc.title: A Novel Process Analytical Technology (TVIS) for the Prediction of Micro-Collapse during a Freeze-Drying Process dc.contributor.author: Jeeraruangrattana, Y.; Pandya, B.; Vhokiwa, H.; Shah, S.; Smith, Geoff

  • dc.title: Application of Impedance Based Technology to investigate the Collapse of Freeze-dried Sugar-salt Solutions dc.contributor.author: Jeeraruangrattana, Y.; Polygalov, E.; Ermolina, I.; Smith, Geoff

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Key research outputs

Smith, G., Arshad, M.S., Polygalov, E., Ermolina, I., McCoy, T.R., Matejtschuk, P. (2017). Process Understanding in Freeze-Drying Cycle Development: Applications for Through-Vial Impedance Spectroscopy (TVIS) in Mini-pilot Studies. Journal of Pharmaceutical Innovation, 12 (1), pp. 26-40

Arshad, M.S., Smith, G., Polygalov, E., Ermolina, I. (2014). Through-vial impedance spectroscopy of critical events during the freezing stage of the lyophilization cycle: The example of the impact of sucrose on the crystallization of mannitol. European Journal of Pharmaceutics and Biopharmaceutics, 87 (3), pp. 598-605

Smith, G., Polygalov, E., Arshad, M.S., Page, T., Taylor, J., Ermolina, I. (2013) An impedance-based process analytical technology for monitoring the lyophilisation process. International Journal of Pharmaceutics, 449 (1-2), pp. 72-83

Smith, G., Arshad, M.A., Polygalov, E., Irina Ermolina, I. (2013) Factors Affecting the Use of Impedance Spectroscopy in the Characterisation of the Freezing Stage of the Lyophilisation Process: the Impact of Liquid Fill Height in Relation to Electrode Geometry. AAPS PharmSciTech, online first

Smith, G., Arshad, M.S., Polygalov, E. and Ermolina, I. (2013) An application for impedance spectroscopy in the characterisation of the glass transition during the lyophilization cycle: The example of a 10% w/v maltodextrin solution. European Journal of Pharmaceutics and Biopharmaceutics, 86 (3 Part B), pp. 1130-1140

Smith, G., Polygalov, E. & Page, T. (2011) A method for monitoring and/or controlling process parameters of a lyophilisation process. British patent application 2480299. Application Number 1007961.4. Filing date 12.05.2010

Research interests/expertise

  • Freeze-drying process development
  • Process analytical technologies (novel sensors in process understanding and control)
  • Impedance spectroscopy, dielectric spectroscopy, terahertz spectroscopy and terahertz imaging, dynamic laser speckle, electrostatic measuremnst of powder flow
  • See current PhD projects for more information.

Areas of teaching

  • Pharmaceutical Sciences
  • Good Manufacturing Practice
  • Pharmaceutical Quality by Design
  • Freeze-Drying
  • Preformulation

Qualifications

  • PhD. Mechanims of Action of Cryoprotectant 1991
  • BPharm 1985 University of Bath

Courses taught

  • BSc Pharmaceutical and Cosmetic Sciences
  • MSc Pharmaceutical Quality by Design

Membership of external committees

 

Membership of professional associations and societies

 

Projects

 (TVIS)

Forthcoming events

 

Conference attendance

Smith   G. (2018) Through-Vial Impedance Spectroscopy (TVIS). A new process   analytical technology for freeze-drying process development. Podium   presentation at: SMi 6th Annual Conference on Pharmaceutical Freeze-Drying   Technology, 2018 June 13-14th, Holiday Inn Kensington Forum, London, United   Kingdom 
Smith G. (2018) Through-Vial Impedance Spectroscopy (TVIS). A   Novel Process Analytical Technology for the Development of Pharmaceutical   Products and Processes.Podium presentation at 2nd Annual Lyophilization   Summit, Vienna, Austria, May 24-25th 2018
Smith   G. (2018) Through Vial Impedance Spectroscopy (TVIS): Dual-Electrode System   for Process Parameter Determination. Podium presentation at  ISL-FD Midwest Chapter Annual Meeting,   Midwest Conference Centre, Northlake, IL 60164, USA, April 12th 2018
Smith   G. Through Vial Impedance Spectroscopy (TVIS): A Novel Approach in the   Development of Freeze-Drying Processes for Drug Products. Podium presentation   at 10th International Workshop on Impedance Spectroscopy, 2017 September   27-29, Chemnitz, Germany
Smith,   G. (2017) Recent Advances in Through Vial Impedance Spectroscopy (TVIS) for   Process Parameter Determination. ISL-FD Conference April 26-28th 2017.   Havana, Cuba
Smith,   G. (2017) Applications for Through Vial Impedance Spectroscopy (TVIS) in   Process Parameter Determination. LyoTalk Dublin, May 22 2017
Smith, G. (2016)  The   Application of Through Vial Impedance Spectroscopy (TVIS)  for Process Parameter Determination in   Freeze-Drying Method Development. PDA Europe. Pharmaceutical Freeze Drying   Technology. Strasbourg, 27 – 28 September 2016
Smith, G. (2016) Through Vial Impedance Spectroscopy. SMi   Lyophilisation Europe, Kensington, London, United Kingdom 4-5 July 2016
Smith, G. (2015) Process Analytical Technology and the Question   of Scale. ISL-FD 2015 International Society of Lyophilization – Freeze Drying   Conference and Seminar. College of Pharmacy, Barcelona, 8-10 July 2015
Smith, G. (2015) A focus on PAT in freeze-drying. APS Parenteral   Focus Group meeting on Freeze Drying and Alternative Drying Technologies for   Parenterals, Burleigh Court, Loughborough University.28 January 2015

Consultancy work

We currently offer our expertise in freeze-drying process development to assist pharmaceutical companies in the development of optimized freeze-drying cycles. Through the application of new process analytical technologies (LyoDEA) we can reduce your development time while delivering a shorter cycle time.

This will reduce the materials consumed in development, accelerate your product to market, and provide you with a more efficient process hence reduce the cost of manufacture.

Externally funded research grants information

EXTALcoat : External Lubrication Coating Inspection System by Dynamic Laser Speckle Imaging (grant ref. )

£115,054 Feasibility Study

March 1 2018 to  February 28 2019

Funding body : Innovate UK

Partners: Gasfill Ltd (Micron Design), Nutrapharma, Merlin Powder Characterization, S3 Process, Â鶹ƵµÀ

 

FastLyo (grant ref. )

£99,849 Feasibility Study

March 1 2018 to  February 28 2019

Funding body : Innovate UK

Partners: Biopharma Process Solutions, OnkoLytika, Â鶹ƵµÀ

 

AtlasBio (grant ref. )

£803 846 Collaborative R&D

February 1 2017 to  January 31 2020

Funding body : Innovate UK

Partners: GEA, BlueFrog, CPI, 

OnkoLytika, IS Instruments, Ocean Optics,

National Institute for Biological Standards and Control, Nottingham University, Â鶹ƵµÀ

 

BioStaRT (grant ref. )

£367 567 Collaborative R&D

August 1 2014 to Jan 31 2018

Funding body : Innovate UK

Partners: GEA, BlueFrog, Sanofi (Ireland)

National Institute for Biological Standards and Control, Â鶹ƵµÀ    

 

LyoDEA (grant ref. )

£217 160 Collaborative R&D

November 1 2008 to October 31  2012

Funding body : Technology Strategy Board

Partners: GEA, AstraZeneca, Ametek, Â鶹ƵµÀ

Published patents

Smith, G, and Polygalov E. (2007). Apparatus for measuring the dielectric properties of conductive materials. British patent 0704880.4 Filing date 13 March 2007. Publication number GB2447477 17 September 2008

Smith, G., Polygalov, E. and Page, T. (2011) A method for monitoring and/or controlling process parameters of a lyophilisation process. GB patent GB2480299 (A). Application number GB20100007961 20100512. Priority date 12 May 2010. Published 16th November 2011

TVIS : Through Vial Impedanace Spectroscopy

The freeze-drying cycle comprise three stages, of pre-freezing (to form ice and to crystallise out any solutes with a propensity to crystallise), primary drying to remove the ice phase, and secondary drying to remove the water which is physic-sorbed to the remaining matrix or crystalline and amorphous solids. Process optimization and scale up requires measurement technologies for characterising each stage of the process. In the freezing stage, it is essential to maximise the amount of ice that forms and to optimise the ice structure in order to facilitate sublimation in the primary drying phase. In primary drying it is essential that the product temperature is as high to reduce the drying time, while maintaining it below certain critical temperatures (e.g. eutectic temperature if the unfrozen phase is largely crystalline and the glass transition if the unfrozen phase is largely amorphous) in order to avoid collapse (from melting and/or loss of structural viscosity.

Process analytical techniques for achieving these challenges goals are limited. Thermocouples are used primary for the detection of crystallization (primary phase transitions) but are ineffective at detecting the glass transition and collapse. Pressure rise testing is used in primary drying, and through modelling of the system can be used to control the temperature at the sublimation interface, and hence optimise the drying process. However, the thermocouple is invasive and may itself alter the ice crystal structure (and hence drying profile), whereas the pressure rise testing model relies on many assumptions in the model which provides an average batch measurement across the drier, and only works in the early phase of drying when there is a steady state condition.

The Pharmaceutical Technologies Group has developed a new approach for process understanding for freeze-drying cycle development, which uses a through vial impedance measurement (TVIS) to characterise a broad range of features of the process, including, ice onset times, the completion of ice solidification, the glass transition, and the structural relaxation of the unfrozen solid, and the primary drying rate and end point. The on-going development of this technology will see the application with micro-titre plate technologies for formulation screening (micro-scale down) and for scale up into production by using a non-contact probes for monitoring problematic regions within the drier.

 Key References

Arshad, M.S. Smith, G., Polygalov, E., Ermolina, I. (2014). Through-vial impedance spectroscopy of critical events during the freezing stage of the lyophilization cycle: The example of the impact of sucrose on the crystallization of mannitol. Eur J Pharm Biopharm., 87, (3), pp. 598-605

Smith, G.; Arshad, Muhammad Sohail; Polygalov, E., Ermolina, I. (2014). Through-Vial Impedance Spectroscopy of the Mechanisms of Annealing in the Freeze-Drying of Maltodextrin: The Impact of Annealing Hold Time and Temperature on the Primary Drying Rate. J Pharm. Sci., 103, (6), 1799-1810

Smith, G., Arshad, M.A., Polygalov, E., Ermolina, I. (2013) Factors Affecting the Use of Impedance Spectroscopy in the Characterisation of the Freezing Stage of the Lyophilisation Process: the Impact of Liquid Fill Height in Relation to Electrode Geometry. AAPS PharmSciTech, online first

Smith, G., Arshad, M.S., Polygalov, E. and Ermolina, I. (2013) An application for impedance spectroscopy in the characterisation of the glass transition during the lyophilization cycle: The example of a 10% w/v maltodextrin solution. European Journal of Pharmaceutics and Biopharmaceutics, 86 (3 Part B), pp. 1130-1140

Smith, G., Polygalov, E., Arshad, M.S., Page, T., Taylor, J., Ermolina, I.  (2013) An impedance-based process analytical technology for monitoring the lyophilisation process. International Journal of Pharmaceutics, 449 (1-2), pp. 72-83

Smith, G., Arshad, M.S., Polygalov, E. and Ermolina, I. (2013) An application for impedance spectroscopy in the characterisation of the glass transition during the lyophilization cycle: The example of a 10% w/v maltodextrin solution. European Journal of Pharmaceutics and Biopharmaceutics, 86 (3 Part B), pp. 1130-1140

Smith, G., Polygalov, E. & Page, T. (2011) A method for monitoring and/or controlling process parameters of a lyophilisation process. British patent application 2480299. Application Number 1007961.4. Filing date 12.05.2010