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: De Montfort University, The Gateway, Leicester, LE1 9BH.

T: +44 (0)116 250 6298

E: gsmith02@dmu.ac.uk

W: https://www.dmu.ac.uk/pharmaceutical

Social Media: uk.linkedin.com/in/gsmith02

 

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 De Montfort 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. Through his 2015 DIRECT programme he has shaped an industry based collaboration of companies to develop improved methods for materials selection for direct compression tableting, coupled to optimised engineering solutions and DMU's novel process senors, to transform DC into a versatile, flexible manufacturing process capable of processing more drug candidates.

In the medical field he has developed research projects into applications for THz imaging for diagnosing melanoma with Leicester Royal Infirmary (funded by Hope Against Cancer).

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 Montfort University'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 

  • Through-Vial Impedance Spectroscopy (TVIS): A New Method for Determining the Ice Nucleation Temperature and the Solidification End Point
    Through-Vial Impedance Spectroscopy (TVIS): A New Method for Determining the Ice Nucleation Temperature and the Solidification End Point Smith, Geoff; Jeeraruangrattana, Yowwares
  • Correlation between molecular dynamics and physical stability of two milled anhydrous sugars: lactose and sucrose
    Correlation between molecular dynamics and physical stability of two milled anhydrous sugars: lactose and sucrose Smith, Geoff; Hussain, Amjad; Bukhari, Nadeem Irfan; Ermolina, I. The process of milling often results in amorphization and the physical stability of amorphous phase is linked with its molecular dynamics. This study focuses on a propensity of two disaccharides (lactose and sucrose) to amorphize on ball milling and the stability of the resultant amorphous phase. The amorphous content in milled sugars is estimated by Differential Scanning Calorimetry (DSC) and the stability was measured in terms of the tendency to recrystallize by Broadband Dielectric Spectroscopy (BDS). The results show that the amorphous content increases with milling time and is greater for lactose than sucrose. At the same degree of amorphization, sucrose recrystallize at temperature ∼15 °C higher than lactose, indicating higher stability. The molecular dynamics (beta relaxation process), suggest that milled sucrose is more stable with higher activation energy (∼9 kJ mol−1) than that of lactose. The moisture content of amorphous phase also impacts its molecular dynamics in terms of increase in activation energy as the moisture decrease with increasing the milling times. The study suggests a greater stability of amorphous sucrose and susceptibility of milled lactose to recrystallize, however, on extended milling when the moisture content decreases, lactose was seen to become relatively more stable. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Solubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipients
    Solubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipients Smith, Geoff; Pedge, Nicholas; Khan, Karrar A; Bukhari, Nadeem Irfan; Hussain, Amjad; Ermolina, I. The aim of this study was to enhance the kinetic solubility and dissolution rate of ibuprofen by co-milling with different excipients and to establish the underlying mechanism(s) for such enhancement. In the first-part, two excipients (HPMC and soluplus) were selected from seven, and the optimal ball-milling parameters of speed and time (18 Hz, 15 min) were determined based on solubility-enhancement and flow-ability criteria. In the second-part, co-milling of different weight-ratios of ibuprofen-to-excipient was carried out and solubility and dissolution rates were determined. Mechanisms of biopharmaceutical enhancement were studied by SEM, laser diffraction, DSC, and FTIR analysis of the co-mixtures. Ibuprofen solubility (0.09 mg/mL for un-milled) was increased by factors of 4–5 and 10–20 for HPMC and soluplus, respectively. The weakening of crystals, stabilization of the amorphous phase and an increase in solid-state hydrogen bonding are the likely mechanisms for this enhancement. Reductions in Q70% dissolution time were also observed, by a factor of 4 and 7 for ibuprofen:HMPC and ibuprofen:soluplus co-milled mixtures, respectively. Although, there were similar reductions in particle size, dispersibility and degree of amorphization in both mixtures, the higher dissolution rate for soluplus, over that for HPMC, must be due to the additional solubilization contribution to the kinetic solubility provided by soluplus. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations Containing Sugars and Polyol: II. BSA Reconstitution and Aggregation
    Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations Containing Sugars and Polyol: II. BSA Reconstitution and Aggregation Hackl, E. V.; Darkwah, Joseph; Smith, Geoff; Ermolina, I. The current paper continues our study on the ability of L-arginine to prevent/reduce the aggregation of proteins that results from the various stresses during the lyophilisation and/or storage of lyophilized protein-based products. The first part of our study, i.e. formulation development, was devoted to the rational design and optimization of an L-arginine containing lyophilized formulation which can resist the natural tendency of L-arginine to absorb atmosphere moisture. Mannitol and trehalose were chosen among other excipients to be included in the protein-based formulation, as mannitol in a combination with L-arginine has been shown to reduce moisture sorption while trehalose provides a degree of lyoprotection. In the present study, a number of formulations, which comprised bovine serum albumin (BSA) with and without L-arginine, and with five different ratios of trehalose-to-mannitol (from 30:70 to 80:20) were lyophilised and assessed. The internal structures and the moisture sorption/retention of the lyophilized formulations were characterised. To study the effect of L-arginine on BSA solid-phase stability, the lyophilized powder was exposed to accelerated storage conditions (high moisture (75% RH) and temperature (22 or 45 °C)) for up to 24 h. The lyophilized BSA formulations were then reconstituted and solution-state protein aggregation assessed by turbidimetry at 360 nm and fluorescence spectroscopy using the thioflavin T assay. It was demonstrated that L-arginine can be used in protein-based freeze-dried formulations to significantly reduce the aggregation of protein during the manufacturing, storage and subsequent reconstitution. The results also revealed the importance of a sufficient amount of mannitol in the arginine-containing formulations. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • The application of dual-electrode through vial impedance spectroscopy for the determination of ice interface temperatures, primary drying rate and vial heat transfer coefficient in lyophilization process development
    The application of dual-electrode through vial impedance spectroscopy for the determination of ice interface temperatures, primary drying rate and vial heat transfer coefficient in lyophilization process development Smith, Geoff; Jeeraruangrattana, Yowwares; Ermolina, I. Through vial impedance spectroscopy (TVIS) is a product non-invasive process analytical technology which exploits the frequency dependence of the complex impedance spectrum of a composite object (i.e. the freeze-drying vial and its contents) in order to track the progression of the freeze-drying cycle. This work demonstrates the use of a dual electrode system, attached to the external surface of a type I glass tubing vial (nominal capacity 10 mL) in the prediction of (i) the ice interface temperatures at the sublimation front and at the base of the vial, and (ii) the primary drying rate. A value for the heat transfer coefficient (for a chamber pressure of 270 µbar) was then calculated from these parameters and shown to be comparable to that published by Tchessalov (2017). The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Effect of arginine on the aggregation of protein in freeze-dried formulations containing sugars and polyol. 1. Formulation development
    Effect of arginine on the aggregation of protein in freeze-dried formulations containing sugars and polyol. 1. Formulation development Hackl, E. V.; Darkwah, Joseph; Smith, Geoff; Ermolina, I. L-arginine was introduced into protein-based freeze-dried formulations to study the ability of arginine to reduce / prevent from protein aggregation during manufacturing, storage and reconstitution of lyophilized protein-based pharmaceuticals. As L-arginine is known to be very hygroscopic, additional excipients which could provide a moisture buffering capacity need to be introduced into the formulation. In the first part of our study – excipient formulation development – the screening of a number of sugars/polyols has been done in order to select the best combination of excipients that, in a complex with L-arginine, can i) produce freeze-dried cakes with elegant appearance, adequate mechanical properties and reconstitution times, and ii) resist/minimize the moisture sorption. Various freeze-dried cakes containing L-arginine in combination with mannitol, trehalose, lactose, and sucrose were produced and analyzed by TGA, DSC, texture analysis, moisture sorption, cake shrinkage, TVIM and SEM. The non-linear dependencies of the physicochemical properties of the freeze-dried cakes on the sugar-to-mannitol ratios were found. The best combinations of excipients (L-arginine, mannitol and trehalose) were selected to be used in the second part of this work, in which the impact of each selected formulation will be studied in relation to the aggregation of a protein. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Micro-structural analysis of tablet surface layers by intelligent laser speckle classification (ILSC) technique: An application in the study of both surface defects and subsurface granule structures
    Micro-structural analysis of tablet surface layers by intelligent laser speckle classification (ILSC) technique: An application in the study of both surface defects and subsurface granule structures Orun, A.; Smith, Geoff Purpose : As a consequence of the latest developments in laser technologies it is now possible to develop a low-cost and accurate tablet inspection system by the unification of optical and artificial intelligence methods. Method: The functionality of the proposed system is based on a sequence of texture analysis of laser speckle images (using laser sources of 650 nm and 808 nm : VIS/IR) followed by the optimization of texture parameters using Bayesian Networks (BN). Results: In the first part of this work, a Bayesian inference method was used to detect micro-scale tablet defects that are generated “progressively” during production whereas in the second part a Bayesian classifier method was used to discriminate between tablets made from different granule sizes. In part two, it was shown that (i) the comparatively higher energy (5mW) IR laser light generates different speckle effects than the lower energy visible (Red 3mW) by interacting with deeper sub-surface of the tablets and (ii) by using multi-classifier systems (MCS) to fuse the Bayesian classifiers from both types of speckle images it was possible to achieve a higher discrimination power (88% classification accuracy) for distinguishing between tablets made from different granule sizes than one can achieve from a single image type. Conclusion: It is suggested that this unified method has the potential to provide for a comprehensive analysis of both tablet quality attributes, on the one hand, and failure modes, on the other, that might be used in the development of a low cost tablet inspection system. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Applications for Through Vial Impedance Spectroscopy (TVIS) in Process Parameter Determination
    Applications for Through Vial Impedance Spectroscopy (TVIS) in Process Parameter Determination Smith, Geoff
  • Recent Advances in Through Vial Impedance Spectroscopy (TVIS) for Process Parameter Determination
    Recent Advances in Through Vial Impedance Spectroscopy (TVIS) for Process Parameter Determination Smith, Geoff
  • 3D non-invasive inspection of the skin lesions by close-range and low-cost photogrammetric techniques
    3D non-invasive inspection of the skin lesions by close-range and low-cost photogrammetric techniques Orun, A.; Goodyer, E. N.; Smith, Geoff In dermatology, one of the most common causes of skin abnormality is an unusual change in skin lesion structure which may exhibit very subtle physical deformation of its 3D shape. However the geometrical sensitivity of current cost-effective inspection and measurement methods may not be sufficient to detect such small progressive changes in skin lesion structure at micro-scale. Our proposed method could provide a low-cost, non-invasive solution by a compact system solution to overcome these shortcomings by using close-range photogrammetric imaging techniques to build a 3D surface model for a continuous observation of subtle changes in skin lesions and other features. The main research group is CCI in collaboration with HLS (School of Pharmacy) Open Access article

Click here for a full list of Geoff Smith's publications and outputs.

Key research outputs

Darkwah, J., Smith, G., Ermolina, I. and Mueller-Holtz, M. (2013) A THz spectroscopy method for quantifying the degree of crystallinity in freeze-dried gelatin/amino acid mixtures: An application for the development of rapidly disintegrating tablets. International Journal of Pharmaceutics, 455, (1-2), pp. 357-364

Ermolina, I., Darkwah, J. and Smith, G. (2013) Characterisation of Crystalline-Amorphous Blends of Sucrose with Terahertz-Pulsed Spectroscopy: the Development of a Prediction Technique for Estimating the Degree of Crystallinity with Partial Least Squares Regression. AAPS PharmSciTech, online first

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

  • Pharmaceutical processing (tableting, micronization, freeze-drying process development)
  • Process analytical technologies (novel sensors in process understanding and control)
  • Impedance spectroscopy, dielectric spectroscopy, terahertz spectroscopy and terahertz imaging
  • Amorphous materials characterization and stability
  • See current PhD projects for more information.

Areas of teaching

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

Qualifications

  • PhD. Mechanimsof Action of Cryoprotectant 1991 (recipient of the Patani Gold Medal)
  • BPharm 1985 University of Bath

Courses taught

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

Membership of external committees

Academy of Pharmaceutical Sciences Focus Group: Process Engineering and Product Formulation. Committee member from November 2012 

Academy of Pharmaceutical Sciences Focus Group: Parenterals. Committee member from January 2014

Membership of professional associations and societies

Academy of Pharmaceutical Sciences

Projects

BioStart. A Collaborative R&D programme funded by the Technology Strategy Board aimed at improving the stability of biopharmaceuticals through the developmen tof novel process analytical technologies for microscale down (formulation scrrening) and scale up (process development).

DIRECT. A Collaborative R&D programme aimed at developing material screening technologies, engineering solutions and process analytical science for the implementation of direct compression tableting processes.

Forthcoming events

“Process Analytical Technology and the Question of Scale” Invited talk at the ISL-FD 2015 International Society of Lyophilization – Freeze Drying Conference and Seminar, College of Pharmacy, Barcelona, 6-10 July 2015 http://islyophilization.org/2015-barcelona/

“Through vial impedance spectroscopy as a tool for the concurrent development of the freeze-drying process and product” Invited talk at the SMi Group 3rd Annual UK Conference on Lyophilisation; Protecting Drug stability and Optimising Formulation Development through Robust PAT and QbD Principles. Holiday Inn Regents Park Hotel, Central London, UK, 29th -30th June 2015

 “PAT in the freeze drying of parenteral products” Invited talk at the Lyophilisation and Freeze Drying USA Conference, Renaissance Woodbridge Hotel, Iselin, New Jersey, USA April 29th & 30th 2015

 

Conference attendance

Seker, H., Uslan, V., Orun, A., Goodyer, E. Smith, G. (2014) Prediction of skin ages by means of multi-spectral light sources, 36th Annual International IEEE EMBS Conference., Chicago 26-30 August, 2014, USA.

Orun, A., Seker, H., Goodyer, E.N., Smith, G, Uslan, V.  (2014) An improvement of skin aging assessment by non-invasive laser speckle effect:  A comparative texture analysis. 2nd International Conference on Biomedical and Health Informatics, BHI2014, Valencia, Spain, 2014

Arshad, M.S. Smith, G., Polygalov, E., Ermolina, I., Page, T., Taylor, J., Birkmire, A., (2014). An application of through vial impedance spectroscopy (TVIS) as a temperature measurement system during freeze drying: the example of lactose 3% w/v solution. AAPS annual meeting and Exposition. San Diego. November 2014

Arshad, M.S. Smith, G., Polygalov, E., Ermolina, I. Mudhar, K., Page, T., Taylor, J., Birkmire, A., (2013). In situ characterization of phase separation in PVP/dextran solution using Impedance spectroscopy. AAPS Annual Meeting and Exposition. San Diego. November 2013

Hussain, A., Ermolina, I., Bukhari, N.I., Smith, G.,  Study of Changes in Crystallinity of Ball Milled Mefenamic Acid using Terahertz Pulsed Spectroscopy. APS UK PharmSci 2014, the Science of Medicines, Weston Auditorium Hertfordshire University, Hatfield UK, 8 - 10 September 2014.

Hussain, A., Ermolina, I., Bukhari, N.I., Smith, G., Quantification of Residual Crystallinity of ball milled anhydrous lactose using DSC and terahertz spectroscopy. 11th European Symposium of Thermal Analysis and Calorimetry, Dipoli Congress Centre, Espoo Finland 17 - 21 August 2014.

Arshad, M.S. Smith, G., Polygalov, E., Ermolina, I. (2014).  In-situ characterization of phase changes in lysozyme/trehalose solutions using through vial impedance spectroscopy. APS UK PharmSci 2014, the Science of Medicines, Weston Auditorium Hertfordshire University, Hatfield UK, 8 - 10 September 2014 (podium presentation)

Arshad, M.S., Polygalov, E., Ermolina, I., Smith, G. (2013). Study on the impact of annealing on the primary drying times using impedance spectroscopy. UKPharmSci2013 Edinburgh, September 2nd - 4th 2013

Hussain, A.,  Ermolina, I., Bukhari, N.I.,  Khan, K.A., Smith, G. (2013) Milling and co-milling with various excipients for the improvement of intrinsic dissolution rate of ibuprofen. UKPharmSci2013 Edinburgh, September 2nd - 4th 2013

Arshad, M.S., Mahboubian, A., Stolnik, S., Marlow, M.E., Ermolina, I., Smith, G. (2012) Evaluation of Thermo-Gelation by Impedance Spectroscopy. The Science of Medicines. Academy of Pharmaceutical Sciences Annual Conference. East Midlands Conference Centre. Nottingham. September 12-14th 2012

Hussain, A., Ermolina, I., Bukhari, N.I., Smith, G.(2012) A Study of the Amorphization of Lactose Monohydrate following extended milling times. UK PharmSci 2012, Nottingham, 12th - 14th September 2012

Hussain, A., Ermolina, I., Bukhari, N.I., Smith, G. (2012) Surface percolation of protons for the creation of crystal defects in lactose monohydrate following short milling times. UK PharmSci 2012, Nottingham, 12th-14th September 2012

Marlow, M.E., Seker, H. and Smith, G. (2012) Characterisation of amorphous and crystalline domains using terahertz spectroscopy. The Science of Medicines. Academy of Pharmaceutical Sciences Annual Conference. East Midlands Conference Centre. Nottingham. September 12-14th 2012

Mueller-Holtz, M.  et al. (2012) Assessment of Microneedle Intradermal Penetration Depth using Terahertz Pulsed Imaging. The Science of Medicines. Academy of Pharmaceutical Sciences Annual Conference. East Midlands Conference Centre. Nottingham. September 12-14th 2012

MahboubianA, Stolnik S, Arshad MS, Marlow M, Smith G. Novel methods for evaluating in-situ gelation using terahertz and dielectric spectroscopy. UKICRS 2012, Aston University, Birmingham, UK, May 2, 2012.

Arshad MS, Ermolina I, Polygalov E, Smith G. In situ impedance measurement of mannitol crystallization during the lyophilisation cycle using LyoDEA™. UK-PharmSci, Nottingham UK, September, 12th -14th 2012.

Arshad MS, Ermolina I, Polygalov E, Smith G. LyoDEA™ measurement of the glass transition of sucrose within a freeze-drying vial. UK-PharmSci, Nottingham UK, September, 12th -14th 2012.

Nazari, K. , Ermolina,  I., Smith, G. (2011). Measuring the base thickness of lyophilisation vials by terahertz pulsed imaging. UKPharmSci2011 Nottingham, August 31st - September 2nd 2011

Darkwah, J., Ermolina,  I. , Smith, G. (2011). Identifying the characteristics of the terahertz absorption spectra of a crystalline binary system containing proline and serine. UKPharmSci2011 Nottingham, August 31st - September 2nd 2011

Wall, L.A. et al. (2011) Evaluating lactose content within Avicel® PH-101 tablets by computational analyses of terahertz waveforms. UKPharmSci2011 Nottingham, August 31st - September 2nd 2011

Smith G, Arshad MS, Ermolina I. Lyosense™. An evaluation of the impact of electrode design on the freezing onset times in the lyophilisation process. UK-PharmSci, Nottingham UK, 31st August- 2nd September 2011.

Darkwah, J., Smith, G. and Ermolina, I. (2010) Terahertz pulsed spectroscopy study of amino acids and gelatin. Journal of Pharmacy and Pharmacology, 62 (10), pp. 1477-1478

Ermolina, I. and Smith, G. (2010) Dielectric spectroscopy of low-losses sugar lyophiles: III. The influence of moisture on the dielectric response of freeze-dried lactose. Journal of Non-Crystalline Solids, 357 (2) pp. 671-676

Ermolina, I., Pandya, A. and Smith, G. (2010) Comparative study of freeze-dried disaccharides by dielectric spectroscopy with respect to molecular mobility and stability. Journal of Pharmacy and Pharmacology, 62 (10), pp. 1409-1410

Nazari, K., Smith, G. and Ermolina, I. (2010) Spatial map of freeze-drier shelf temperature variations using product collapse as a surrogate temperature probe. Journal of Pharmacy and Pharmacology, 62 (10), pp. 1471-1472

Pandya, A., Ermolina, I., Storey, R., Smith, G. (2010) Relationship between ATP hydrolysis and molecular dynamics in co-freeze-dried sugar-ATP mixtures. Journal of Pharmacy and Pharmacology, 62 (10), pp. 1465-1467

Smith, G., Polygalov, E. and Page, T. (2010) Lyosense (TM) Lyophilisation process control. Journal of Pharmacy and Pharmacology, 62 (10), pp. 1448-1449

Wall, L. A., Ermolina, I. , Gamlen,M. J., and Smith, G. (2010) Use of terahertz time-domain spectroscopy to correlate refractive index and hardness for Avicel PH-101 tablets. Journal of Pharmacy and Pharmacology, 62 (10), pp. 1485-1486

Smith, G. (2010). Lyosense™. Lyophilisation process control. PDA Europe conference. Freeze-Drying. Modern Trends in Production.Vienna. November 23-24th 2010

Fei, D., Ermolina, I. and Smith, G. (2009) A study of the degradation of poly(lactic-co-glycolic acid) films by DRS, DSC and SEM. Journal of Pharmacy and Pharmacology, 61 (S1), A91-A92, Meeting abstract 124

Pandya, A. et al. (2009) High-performance liquid chromatography method development for studying the degradation of freeze-dried adenosine triphosphate when stored at 4 and 40 degrees C.  Journal of Pharmacy and Pharmacology, 61 (S1), A130, Meeting Abstract 177

Smith, G. and Ermolina, I. (2009) Dielectric relaxation in freeze-dried disaccharides: developments in our understanding of the potential significance to moisture buffering of freeze-dried products.  Journal of Pharmacy and Pharmacology , 61 pp. A68-A69

Smith, G. and Ermolina, I. (2009). Dielectric relaxation in freeze-dried disaccharides: developments in our understanding of the potential significance to moisture buffering of freeze-dried products. Journal of Pharmacy and Pharmacology 61: A68-A69.

Smith, G. et al. (2009) Measurement of amorphous lactose stability by terahertz spectroscopy. Journal of Pharmacy and Pharmacology, 61 (S1), pp. A3-A4, Podium presentation

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.

Current research students

Supervisor

Role

Student

Mode

Funding Source

Smith, Geoff

1st

Sohail Muhammad Arshad

Graduated 2014

University of Lahore & AstraZeneca

Smith, Geoff

2nd

Joseph Darkwah

FT

Self

Smith, Geoff

1st

Amjad Hussain

FT

University of Lahore

Smith, Geoff

1st

Martin Mueller-Holtz

FT

Hope Against Cancer

Smith, Geoff

1st

Amee Pandya

Graduated 2014

AstraZeneca and Agilent

Smith, Geoff

1st

Alex Wall

FT

DMU 2009 Scholarships

Externally funded research grants information

BioStaRT. Biopharmaceutical Syability at Room Temperature. Geoff Smith. Principal Investigator. Technology Strategy Board Grant for Collaborative R&D. June 2014 to May 2017. Collaborators: GEA Pharma Systems, BlueFrog Design, NIBSC, Genzyme Ireland

LyoDEA. In-process sensing technology for control of the freeze-drying cycle. Geoff Smith. Principal Investigator. Technology Strategy Board Grant for Collaborative R&D. Nov 2008 to Oct 2012. Collaborators: GEA Pharma Systems, AstraZeneca, Ametek

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

LyoDEA: 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 (LyoDEA) 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

 

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