51³Ô¹Ïapp

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 De 51³Ô¹Ïapp University 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 De 51³Ô¹Ïapp University's Pharmaceutical Quality by Design programme, with a wide range of industrial practitioners providing webinars on elements of quality by design.

 

Pharmaceutical Technologies 

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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

• 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.

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

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

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

 

 

 (TVIS)

 

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

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.

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, De 51³Ô¹Ïapp University

 

FastLyo (grant ref. )

£99,849 Feasibility Study

March 1 2018 to  February 28 2019

Funding body : Innovate UK

Partners: Biopharma Process Solutions, OnkoLytika, De 51³Ô¹Ïapp University

 

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, De 51³Ô¹Ïapp University

 

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, De 51³Ô¹Ïapp University    

 

LyoDEA (grant ref. )

£217 160 Collaborative R&D

November 1 2008 to October 31  2012

Funding body : Technology Strategy Board

Partners: GEA, AstraZeneca, Ametek, De 51³Ô¹Ïapp University

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

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