15. Advanced Sorption Instruments for Powder Characterisation
Submitting Institution
Imperial College LondonUnit of Assessment
Aeronautical, Mechanical, Chemical and Manufacturing EngineeringSummary Impact Type
TechnologicalResearch Subject Area(s)
Chemical Sciences: Analytical Chemistry, Macromolecular and Materials Chemistry, Physical Chemistry (incl. Structural)
Summary of the impact
Novel vapour sorption experimental methods for the characterisation of
complex particulate materials have been developed in the Department of
Chemical Engineering. This research and expertise resulted in the creation
of Surface Measurement Systems Limited (SMS), whose Dynamic Vapour
Sorption (DVS) and Inverse Gas Chromatography (IGC) instruments are now
found in >500 laboratories around the world. They are recognised
standard research and development tools in the global pharmaceutical
industry (DIN 66138). SMS has contributed >270 man-years of employment
and generated £27M of turnover, whilst SMS instruments have generated over
£300M of economic value, over the REF period.
Underpinning research
The growth in the development of new solid state pharmaceuticals during
the past 20 years revealed a significant knowledge and understanding gap
in the physicochemical stability, and especially the moisture stability,
of these complex organic solids. This is important as these materials
underpin a £10Bn UK industry, and this knowledge deficiency in turn
represented a bottleneck in development of new solid state dosage forms.
Research on the use of vapour molecules as a method for characterising
solid state materials is a key research interest of Dr. Williams (in post
1993-date). His initial research focused on refining the technique known
as Inverse Gas Chromatography (IGC). In this technique an unknown powder
is packed into a small column the size of a pencil, and its surface and
bulk properties are determined by eluting known vapour molecules through
the column using a gas chromatographic approach. PhD students who worked
on IGC and related techniques included N.Zafeiropoulos (1998-2002),
P.Yla-Maihaniemi (2001-4) J.Heng (2002-5), R.Ho (2005-8) and , J.Khoo
(2006-2010). Funding for IGC related work in this period included EPSRC,
Unilever, Syngenta, Givaudan, Du Pont, GSK and Astra-Zeneca.
The research performed at Imperial College resulted in breakthroughs in
the refinement of new vapour adsorption instrument approaches as well as
identifying the key industrial research problems for these new measurement
approaches. They key breakthroughs in the instrument approach were: (i)
translation from chromatographic to a gravimetric measurement method [1];
and (ii) the discovery of the sensitivity of these methods to molecular
structure and morphology [2]. These molecular adsorption based
experimental techniques can provide a unique and important insight into
the physicochemical properties of particulate materials such as
pharmaceuticals. In turn, the availability of these new research tools
within the Department of Chemical Engineering opened up a range of new
research opportunities with industry.
Early work on the moisture stability and performance on pharmaceutical
powders [1] first demonstrated the significant benefits of the DVS method
of measurement in 1994. Specific knowledge on the surface properties of
complex materials such as inhalable drug particles and polymers was then
shown to accessible using the IGC technique [2,3,4]. It has also been
found to be a very powerful way of looking at the effects of processing
history on final product performance [4], while new scientific methods for
determining surface heterogeneity of such materials have been pioneered
using the IGC method [5,6].
References to the research
* References that best indicate quality of underpinning research.
[2] P.S. Thomas, D.R. Williams, "The Characterization Of Thin
Polymer-Films Using Igc ", Abstracts Of Papers Of The American Chemical
Society Vol: 207 Pages: 222-PMSE Part: 2 (1994) ISSN: 0065-7727
*[3] N.E. Zafeiropoulos, C.A. Ballie, F.L. Matthews, D.R. Williams,
"Engineering and characterisation of the interface in flax
fibre/polypropylene composite materials. Part I. Development and
investigation of surface treatments", Vol 33, pp. 1083-1093, (2002)
ISSN:1359-835X DOI: 10.1016/S1359-835X(02)00082-9
*[4] J.Y. Heng, F. Thielmann, D.R. Williams, "The Effects of Milling on
the Surface Properties of Form I Paracetamol Crystals", Pharmaceutical
Research, Vol 23, pp. 1918-1927, (2006) ISSN:0724-8741 DOI:
10.1007/s11095-006-9042-1
*[5] P. Ylä-Mäihäniemi, J.Y. Heng, F. Thielmann, D.R. Williams, "An
Inverse Gas Chromatographic Method for Measuring the Dispersive Surface
Energy Distribution for Particulates", Langmuir, Vol 24, pp. 9551-9557,
(2008) DOI: 10.1021/la801676n
[6] R. Ho, S.J. Hinder, J.F. Watts, J.Y. Heng, D.R. Williams, S. E.
Dilworth "Determination of surface heterogeneity of D-mannitol by sessile
drop contact angle and finite concentration inverse gas chromatography",
Int. Journal of Pharmaceutics, Vol 387, pp. 79-86, (2010) DOI:
10.1016/j.ijpharm.2009.12.011
Details of the impact
Surface Measurement Systems Limited (SMS) was formed by Drs. Briscoe and
Williams from the Department of Chemical Engineering and in 1994, working
in collaboration with Pfizer Research UK, invented a novel gravimetric
instrument for water sorption analysis of powders called Dynamic Vapour
Sorption (DVS). The DVS instrumentation approach is closely linked to the
IGC research work pioneered by Dr Williams at Imperial College funded by
an industrial research contract with Du Pont Fibres. Dr Williams remains
the Managing Director of SMS and in 1997-1999 spent 0.5 FTE working with
SMS (the balance of FTE in post at Imperial College), promoting the DVS
product and working on its commercialisation.
This new DVS approach allowed water sorption isotherms to be obtained 20
times faster, using 20 times less sample and 20 times more accurately [7]
than traditional measurement approaches, thus transforming laboratory
practice in this domain. This advance allowed stability testing,
formulation development and polymorph screening studies to not only be
significantly accelerated, but to be performed with a much higher degree
of scientific certainty. The DVS method has now become a standard method
used by all major pharmaceutical companies throughout the world, and has
been formally adopted within the German DIN 66138 "Isotherm Measurement
for Solids using Vapour Sorption" standard [8].
Advances in IGC research at Imperial College resulted in further
developments at SMS. In 2000 SMS successfully released the world's first
commercial IGC instrument. In 2011 a second generation instrument, called
the Surface Energy Analyser (SEA) which incorporated many of the more
recent scientific discoveries published by researchers at Imperial College
[5,6], was launched. Over 50 of the new SEA systems have been sold in the
first 24 months of sales.
Based upon Imperial College's research on the adsorption characterisation
of solid state materials, instruments subsequently developed by SMS can
now be found in over 500 research laboratories in over 25 different
countries. All 20 of the world's largest pharmaceutical companies use SMS
instruments as do over 100 universities globally. SMS instruments have
accelerated the testing, formulation and development of new solid state
pharmaceutical products for nearly 20 years. Research described in
[1],[4],[5] and [6] highlights some of the critical pharmaceutical
research problems which have led the industrial demand for SMS products.
These scientific applications are a key contribution to the commercial
success of SMS, with SMS selling 60% of their instruments into the
pharmaceutical industry.
SMS has contributed to the innovation capital of the UK, as the global
technological market leader in sorption characterisation instruments. It
has a significant patent portfolio [9, 10,11] as well as a significant
proprietary base in key instrumentation technologies. SMS is an ISO
9001:2008 registered firm, and currently employs 50 staff globally, with
offices in London, France, Germany and the USA. Manufacturing operations
are based in the UK and the USA, with R&D activity based in West
London. The company currently has 10 PhD qualified staff on the payroll,
including a number of Imperial College graduates. It currently invests
>15% of turnover in research and development and has an audited
turnover of ~£5M. 90% of sales are exported from the UK. During the REF
period of Jan. 1st 2008 to 31st July 2013, SMS has contributed > 270
man years of employment, generated £27M of turnover, £24M of export income
and sold > 400 scientific instruments.
It is within the pharmaceutical sector that the instruments from SMS have
had the greatest scientific and commercial impact. For the past 15 years
many of the research and regulatory submissions globally on new drugs
relating to moisture uptake and moisture stability will include data
generated or elucidated using SMS instruments [12]. The impact of these
instruments on the accelerating the development time for bringing new
drugs entering market or in mitigating the risks of bring unstable
products or formulations to market is best reflected by the fact that that
every solid state and pre-formulation group in every major pharmaceutical
company in the world will have DVS type instruments in daily operation;
over 60% of these instruments are manufactured by SMS [7].
Senior Fellow at Novartis states [12]:
"DVS has been established over the past 15 years at Novartis
development in Basel as a standard technique to measure water sorption
in order to support physical stability studies and increase the
understanding of phase transitions such as glass transition/ re
crystallization and polymorphic changes, especially with the advent of
the high throughput version."
To estimate the economic impact of SMS instruments, one can use a
commercial day price for 1 day of DVS or IGC contract test work of £500
(as charged by many universities as well as SMS to industry). Combined
with the practical knowledge that DVS or IGC instruments are run 365/7/24
globally, and assuming a conservative 50% effectiveness, we can estimate
that the current installed base of 700 SMS instruments generates an
economic impact of over £60M annually. During the REF period this
translates globally to over £300M of economic value being generated by SMS
products.
Sources to corroborate the impact
[7] Surface Measurement Systems (SMS) www.smsuk.co.uk
(Archived at
https://www.imperial.ac.uk/ref/webarchive/zrf
on 6th September, 2013)
[8] Deutsches Institut Fur Normung E.V. "Isotherm Measurement for Solids
using Vapor Sorption" (2008) DIN 66138
[9] Williams, Daryl; Briggs., Michael; Jinting Gu, , Wrigley,. Ray
"Method and apparatus for investigating the properties of a solid
material" (2005) GB 2408800B, Filing Date: 24/10/2003
[10] Carl Levoguer, Dylan H Simpson, Daryl R Williams "Controlled sample
environment for analytical devices" (2007) US 7160718 Filing Date:
30/05/2001
[11] David A. Butler, Carl Levoguer, Daryl R. Williams "Apparatus and a
method for investigating the properties of a solid material by inverse
Chromatography" (2002) US 6490910, Filing Date 08/10/1999
[12] Senior Fellow, Novartis Pharma AG, to confirm that many of the
research and regulatory submissions globally on new drugs relating to
moisture uptake and moisture stability include data generated or
elucidated using SMS instruments.