#FormulaX

Formula X Conference Book - Programme + Abstracts - draft (pdf)

Oral Programme - Poster Programme

The Formulation Science and Technology Group of the Royal Society of Chemistry organised Formula X - Understand, Formulate, Innovate at The University of Manchester, following on from the first Formula in Asia, Formula IX - Multiscale Structures and Functionalities for Future Formulation which happened Beijing in October 2017.  The first Formula conference was held in 1987, 31 years later Formula X continued the tradition of bringing together the best industrial and academic science and engineering which accelerate the application of formulation across Europe.

The conference theme of "Understand, Formulate, Innovate" highlighted the direction of travel for the formulating industries where more research and development is now aimed at developing the understanding before formulation occurs, which is driving new types of innovation.  While traditional formulation science research is still important it is now being applied to more and more complex formulations, and even for the most complex formulation digital techniques are being used to limit the formulation space that needs to be explored.  Formula X once again covered a broad range of formulating industries and the domain specific understanding which is key to successful formulation continued to be a focus, the session chairs were tasked with highlighting cross-domain learning.

Formula X - Summary

     Introduction

        3 years after Formula VIII in Barcelona and 18 months after Formula IX in Beijing, Formula X was back in Europe from 24th to 27th June in Manchester appropriately in the birthplace of the first industrial revolution, Industry 4.0 was the new kid on the block amongst nanoformulations, suspension, emulsion, coatings, scale-up.  Now its all over after 6 keynotes, 44 talks, 27 posters were presented by 147 delegates representing 73 institutions from 10 countries.

        While Formula X’s tag line was “Understand Formulate Innovate”, sustainability was embedded and so the conference itself tried to be sustainable - the conference souvenir was a water bottle meaning water wasn’t supplied in plastic bottles, the conference abstracts were only online, so QR codes were everywhere to find the abstracts to share your email address ...., The University of Manchester ensured any excess food was given to a refuge in Manchester.  Of course the biggest impact will the knowledge that was transferred resulting in more sustainable formulations being manufactured far into the future.

         Even though Formula X is over, we are going to keep all the abstracts online and share all the presentations that can be shared online too.  A special issue of Polymer International is being produced with submitted oral and poster presentations from the conference.

         The conference ran as 2 parallel sessions interspersed with keynotes, poster sessions, flash posters, workshops and the conference dinner at the National Football Museum.

         The parallel sessions were "Advances in Dispersed Systems", "Novel Formulation Development", "Novel Characterisation of Formulations", "Formulation of Pharmaceuticals & Biologicals", "Formulation of Nanomaterials", "Emulsions & Suspensions", "Formulation Processing & Scale-up" and "Innovative Coatings & Films including Functional Surfaces, Wetting & Surface Tension".

         What is formulation?  Product engineering or perhaps even more simply it is stability and instability.  A series of ingredients are combined in a process to produce a product which needs to be stable for most of its life with periods of instability perhaps better described as transitions to a new state of stability - i.e. a shampoo stable in the bottle and then disassembles to remove dirt from hair which it stabilises in dispersion, a paint transitioning from a stable suspension in a can to a solid film on a surface.  So it is hardly surprising that many of the presentations during Formula X mentioned stability either directly or indirectly.

         The Formula conferences have always shown the cross-industry / cross-application nature of the practice of formulation, with pharmaceutical formulation learning from fragrance formulation in washing powders and Formula X continued this tradition in spades.  So this summary of the conference will attempt to highlight the key learning often in one industry as these will be the new lessons for other formulating industries.  If you want all the details, then check the abstracts, see the presentations, read the papers when published or contact the presenters.

         We hope we got the balance right between with the fashionable not overwhelming the reliable, we make no apology that the conference started with graphene and ended with 3-D printing, both with a practical formulation slant, but equally with plenty of content on emulsions and characterisation highlighting how formulation is now been strongly driven by greater understanding of complex systems being applied to real life formulation.

        Like any conference the organisers enable the conference and can make it fail, but success is down to the enthusiastic open sharing of knowledge and needs by the presenters and the delegates.  So the organisers of Formula X would like to acknowledge the energy of all the attendees for its success and look forward to seeing you all at Formula XI.

     Drops

        Evaporation from drops had been a forgotten topic in many ways before coffee rings made the front page of Nature, in reality it had always been a concern for everybody from paints to inhaled drug manufacturers, but it is only relatively recently that tools have existed to allow us to study the phenomena at the drop scale.  Jack Goodall (C-30) discussed his studies of the physical processes which control structuring in single drops of mixed liquids, Hassan Abdullahi (C-51) combined single droplets measurements with modelling to guide scale-up of spray drying and Anna Millqvist & Jakob Sloth Overgaard (K-5) discussed how spray dryer process design was both driven by formulation development and drove it with single droplet studies used to direct formulation development based on the evaporation conditions which will be encountered in the huge spray driers GEA build.

   Industry 4.0

         Once you understand the concept of Industry 4.0, basically control throughout your product from development to manufacture to use, then you can see that all formulation is moving in towards there.  Industry 4.0 is often very digital but in the case of formulation the digital is often only possible once you have an scientific understanding, so saying Industry 4.0 is just digital would miss the huge contribution that advances in theory and measurement have made it possible.  While Industry 4.0 is very good in theory, integrating everything together so it works effectively is a steep learning curve, Dave Berry (C-45) has developed a research facility as a combination of modelling tools, control systems, process analytical technology, powder processing systems and data system which allow new powder formulations to be developed.  The pharmaceutical industry has gone full Industry 4.0 with ADDoPT.  Martin Edwards (C-27) explained how the ADDoPT - Advanced Digital Design of Pharmaceutical Therapeutics information flow enables the digital design and manufacture of formulated drugs.

    Prediction

         Transitioning formulations to more sustainable solvents is a non-trivial task, which Pertu Niga (C-28) explained could be simpler with the RISE Rapid Substitution Tool, combination of the Hansen Solubility Parameters in Practice software with a wide range of other data cost, odour, safety, RISE eye-irritation calculations and physico-chemical properties is able to recommend appropriate more sustainable replacement solvents.

        The need to remove materials of concern requires a focused approach to new formulation development due to the need ingredient substitution which can not be achieved by the incremental development by which current formulations have often been optimised.  Nathalie Sintes-Zydowicz (C-03) used statistical design of experiments to develop non-isocyanate polyurethane nanoparticles, which included biobased monomers.

         Sander van Loon (C-16) showed how high throughput measurements could be used to provide the experimental parameters which enable a theory to predict across a whole ingredient space, where high throughout alone would take centuries to carry out all the measurements despite its speed, in his case Hansen Similarity Parameters (used to be solubility) and Hydrophilic Lipophilic Difference - Net Average Curvature (HLD-NAC) (HLB on steroids, with some science behind it).

    New Ingredients

         While novel formulations with sexy ingredients are great for academic publications to get them into formulations they have to show real benefits and to target the correct systems hypothesis of structure property relationships are required.  Ijeoma Uchegbu (K-2) explained how for nanotechnology in medicine there was a need to got just show one benefit over more conventional medicines but to show many.  So for with nanomedicines based on self assembling polymers and peptides already at the preclinical stage, benefits not just of increased bioavailability are seen, but also positive changes in drug biodistribution.  Along the same lines, graphene has superlative properties, which have long been postulated make it the perfect ingredient for formulations, however despite a Nobel prize in 2004 relatively few formulations currently contain graphene.  Ian Kinloch (K-1) explained the complexities of formulating graphene as with many nanomaterials one of avoiding agglomeration, but also the challenges of maintaining multi-functionality which requires conflicting microstructural requirements, however now a range of stabilisation approaches and hybrid materials combined with microstructural control are delivering on the promise as demonstrated by current use is composites and supercapacitor applications.

         The replacement of oil derived components with bioderived components has been achieved by Chi Chang (C-13) through careful use of a range of rheological techniques to formulate environmentally friendly cosmetic creams with properties that allow manufacture, but also provide the correct application properties.

         In order to combat climate change reduction in the use of volatile solvents is a useful tool, but often "oils" with no ultimate function in the final product are added to allow a hydrophobic ingredient to be delivered in an aqueous formulation as an oil in water emulsion.  Jordi Esquena (C-23) demonstrated the use of water in water emulsions stabilised by particles to remove the need for oil or surfactants.  The water in water emulsions rely on thermodynamic incompatibility between two hydrophilic components, producing a biphasic but aqueous system which is stabilised by particles.  These are attractive as is for fat free food use, but can equally be drug or fragrance delivery vehicles where the active is preferentially held in one of the phases.

         In search for materials to replace surfactants to stabilise emulsions, the use macromolecular species is one approach, here Michel Grisel (C-38) has successfully used octyl modified xanthan to stabilise oil-in-water emulsions with grafting density controlling the bulk-interface partition.

    Stability

         Stability of formulations always scores highly as a key challenge for any formulator, predicting months / years stability from a single laboratory measurement is the dream, in reality stability means many different things depending on the formulation being studied and the environmental stresses it will face during manufacture, transport, storage and use.  Traditional stability tests involve lots of bottle stored under controlled conditions for long periods of time with a lot of manual intervention to both age and study the stability, so rather than a single measurement, protocols which offer either to shorten time and reduce the labour involved or to predict stability are keenly sort.  In concentrated silicone emulsions where the weak gel structure controls stability, Stéphane Ugazio (C-06) has successfully used multiple light scattering and microrheology to be able to select systems which will have good shelf stability.  Leopold Mottet (C-34) has developed an automated system able with minimum manual intervention to age samples and measure a wide range of physical properties which can be used to predict stability.  Not only does the system reduce labour required but the quality of the data as compared to manual assessments means that a large database of stability data can feed machine learning systems to produce a more robust understanding of stability.

         Agrochemicals are not deployed in standardised factories but in fields around the world, so robustness of the formulations are key, primarily stability of emulsions.  Malcolm Faers (C-18) presented a range of techniques to provide physical quantities which predict long term stability and cost effective approaches to improve stability through limit the possibility of gravitational settling.  Even with a stable agrochemical formulation which has been applied to the plant in the correct way, has the weather to deal with and so Niall Thomson (C-36) has used a laboratory rain tower and fluorescent model systems to assess the retention of active ingredients on a leaf surface.

    Better Drugs

         Immunogenicity of a new drug is only detected in clinical trials, so has considerable safety and cost implications, but can in fact be limited to specific formulations or a narrow range of patients.  Sebastian Hansson (C-47) showed how the use of asymmetric-flow field fractionation allows immunogenicity to be detected in pre-clinical tests using human tissues.  Where any immunogenicity is detected the contributing factors can be safely identified i.e. incorrect dose formulation or patient characteristics, potentially allowing the drug to proceed to clinical trials having identified and removed the cause of the immunogenicity.

         Multiple antriretrovirals are required to combat HIV and need to be taken for long periods of time, where these show poor aqueous stability resulting in poor bioavailability then higher doses have be to be used.  Alison Savage (C-33) was able to increase the bioavailability of antiretrovirals in a solid drug nanoparticles, using this approach it has been shown in preclinical studies that reductions of up to 50% of Darunavir and Ritonavir could still maintain drug concentrations in the therapeutic window, scale-up has opened the possibility for human clinical evaluation.

         Alain Durand (C-46) studied treatment efficiency with one of the oldest drug delivery forms, the tablet, which is also very complex with interactions between API - ingredients and effects of the manufacturing processes on the API, all able to either degrade or enhance the ultimate treatment.  The study showed the considerable impact of both excipient and manufacturing conditions through detection of partial API degradation, such studies can guide formulation optimisation.

         Targeted delivery of nucleic acid to cancer cells using nanoparticles was shown by Annalisa Tirella (C-14) using nanoparticles decorated with hyaluronic acid combined with modified chitosans improved targeting of cancer cells and maintained efficacy for longer in storage.

         Chris Fox (C-02) showed that conifer-derived oil-in-water nanoemulsions could replace squalene nanoemulsions as adjuvants in vaccine preparations, as they achieve long-term stability, while stimulating cytokine production from human cells in vitro and antigen specific animal models.

    Novel Encapsulation

         While carotenoids have attractive antioxidant properties and show promise in alleviating chronic diseases, their use is limited by their propensity to oxidative degradation, Isabel Mira (C-17) has studied the stability of microalgal carotenoid-rich extracts formulated as o/w nanoemulsions and nanostructured lipid carriers, using spectrophotometry to study degradation over time under a range of different storage conditions.

         Alain Durand (C-32) through showing that chitosan / carboxymethyl cellulose stabilised poly(lactide-co-glycolide) particles are colloidally stable and able to encapsulate high concentrations of a model hydrophobic drug have the potential to be effective pH-sensitive drug carriers.

         Stephanie Nachtigall (C-39) explained how double emulsions were attractive as delivery vehicles for example by allowing aqueous actives to be kept separated in an aqueous system within a water in oil emulsion dispersed as an oil in water emulsion, but were currently limited by the tendency for the two separated aqueous phases to become one.  This work has taken a combination of modelling and nonlinear spectroscopy to understand the structure and alignment of the emulsifier molecules at the different interfaces to guide selection of the most stable components to overcome the lack of stability.

          Grit Baier (C-43) is using both polyelectrolyte complexes and polymer conjugates as methods to protect a range of enzymes and preserve their function within a formulation, physico-chemical stability of the protected enzyme was characterised to understand stability in the formulation, calorimetry is used to measure the strength of interaction and hence ensure that the enzyme will be available in use to perform its function.

          While the use of hydrogels are increasing due to their Janus solid and liquid like properties depending on stress, as Geraldine Rangel Euzcateguy (C-12) explained understanding the molecular / macromolecule source of these properties is complex but essential to be able to tune the properties.  She has combined rheological and Raman spectroscopy to show how small variations in chemical structure gave control over time to gelation and thermal reversibility.

         While poly(lactic-co-glycolic acid) (PLGA) nanoparticles are effective stabilisers of Pickering emulsions, Nicolas Huang (C-29) set out to study the state of the interface formed.  A comparison of emulsions prepared with PLGA NPs and PLGA sterically stabilised with poly(vinyl alcohol) NPs, physicochemical measurements showed that PLGA-PVA NPs produced a simple O/W emulsions, whereas PLGA NPs produced a complex W/O/W emulsions, this is thought to be due to the PVA desorbing and reducing the interfacial tension.

     Deep Understanding

          Mitha Al-Jabri (C-11) using dissipative particle dynamics (DPD) based simulations was able to study the dissolution of surfactant lamellar phases, giving interesting insights into the effect of changes in hydrophilicity and hydrophobicity on the dissolution process and the type of micelles which are formed.

         A different use of DPD by Charlie Wand (C-37) to calculate energy of scission worm-like micelles, showed how the energy of scission increases with increasing salt concentration and change in alkyl chain from C12 to C16, quadruples the energy of scission.

         Maeva Riegert (C-09) with cement and latex polymers having such different mechanical properties it is surprising that addition of latex to cement improves both mechanical properties, the complexity of the system means that understanding of the interactions is incomplete.  By taking a stepwise approach to study the system, a commercial latex has been split into separate components, studied in cement pore solution (very high pH), interaction with gypsum, as a nonreactive analogue of cement, this has shown that there is a strong attractive interaction between latex and gypsum, this work will now be extended to live cement.

          Fadoua Sallem (C-26) titanium dioxide as nanoparticles is widely used, including ceramics where stable concentrated colloidal suspensions are stabilised by the addition of dispersants.  The dispersant adsorbs on the titanium dioxide surface and controls the nanoparticles Zeta potential and hydrodynamic size.  Studies of both diluted/concentrated suspensions at a range of dispersant ratio and suspension pH, showed that viscosity was controlled by the nanoparticle size.

         Hard surface cleaning is not just a physico-chemical process but also has a chemomechanical component which has received relatively little attention, Perrakis Bistis (C-22) has taken a tribological approach to measure frictional properties and use tribological equipment to study the role of normal load, speed, mass and concentration of surfactant on cleaning.  The results to clean burnt tomato appear to show that it is necessary to apply a minimum normal load to achieve a reasonable cleaning rate with little extra cleaning occurring with additional load, cleaning increases with increasing speed and addition of surfactant has little effect on cleaning.  The surfactant will not only aid cleaning but also lubricate the interface, hence the small effect on cleaning, in application the surfactant would also be dispersing the removed materials and while having little effect on the real cleaning would be perceived to increasing cleaning by stopping redeposition.

         Cleaning systems are designed to remove dirt from surfaces, however in many laundry products functional additives are included which need to deposit during the cleaning process, Evangelia Argentou (C-35) investigated the role of CMC, emulsifying capacity, ions, charge, pH and fabric type on deposition.

         Zeolites have since 1960's had wide application as catalysts in commercial processes, due to their high activity, selectivity and robustness, however their microporous nature limits transport and in the search for more sustainable catalysts, Xiaolei Fan (K-7) explained 2 approaches to introducing mesoporosity post-synthesis.

     Predictable Processes

          The UK's Centre for Process Innovation (CPI) as part of the High Value Manufacturing Catapult has been set up to ensure that research is turned into commercial success by helping with product/process development and scale-up, John Williams (C-44) had distilled some of the learning gained through helping many products across this valley of death.

         Min Zhang (C-24) described the liquid mixing research facility which is being used to both bring on new process analytical technologies (PAT) and build predictive models which enable scale-up.  This was demonstrated through the validation of a new in-line viscometer/rheometer, where experiments on the facility combined with CFD calculations were used.

         Dai Hayward (C-31) demonstrated the benefits of membrane emulsification to efficiency, by generating uniform droplets, using low energy, in a single pass, with high yield and high stability.

         Water-in-oil-in-water are attractive for encapsulation of hydrophilic actives, as long as they can be produced at high efficiency and reproducibly, this is a challenge as production is via sequential emulsifications.  Véronique Schmitt (K-3) showed using rheology and UV-vis spectroscopy that encapsulation efficiencies of 100% could be maintained as long as in the second emulsification step turbulent flow did not lead to excessive fragmentation producing too small drops.  The role of a lipophilic stabiliser in stabilising and controlling release from the inner droplet was studied.  Overall W/O/W if correctly formulated and manufactured can act as efficient delivery mechanisms even after long storage.

     Coatings

          Release coatings are essential for many applications, Aymeric Genest (C-15) showed how improving properties of a silicone system relied on additives, anti-mist to allow faster running, new anchorage additives to enable lower VOC control and anti-foaming additives to reduce waste.

         Corrosion protection coatings are essential to extend the functional life of metals enabling everything form cans to bridge.  Flor Siperstein (C-48) and Simon Gibbon (C-52) talked about the EU funded MarieSklodowska-Curie project SUSTICOAT, where understanding of the dissolution of soluble corrosion inhibitor particles has been simulated with cellular automata and the nano-IR technique has been used to understand how polymer microstructure within a range of different coating systems impacts corrosion protection performance.

         Bio-based alkyd resin are extensively used for coatings as O/W emulsions Jesus Fermin Ontiveros (C-07) has investigated the parameters which control catastrophic phase inversion, allowing conditions to be optimised to minimise the droplet size.

     Speeding Up Formulation

         Achieving the optimal formulation for crude oil emulsifiers is a laborious process involving in field testing, Guillaume Lemahieu (C-08) demonstrating using measurement of Phase Inversion Temperature (PIT) and conductivity-temperature profiles to be guide surfactant selection of different crude oils.

         It is well understood that rheology properties of emulsions are of considerable importance for emulsions used as household products, but the relationship between physico-chemical properties and rheology is not well understood, Ze Nian Koay (C-10) has shown surprisingly that emulsion rheology is largely unaffected by dispersed phase viscosity, but strongly effected by mean emulsion drop size (Sauter mean diameter) and emulsion volume fraction.  This insight will provide simplification of formulation of these complex systems.

        3-D printing and additive manufacture rely on being able to print the required materials, which means effectively formulated inks.  The lack of suitably formulated inks has been identified as the key blocker for uptake of the technology.  Ricky Wildman (K-6) demonstrated how a methodology based on high throughput and fast assay process has been able to reduce the time required to formulate an ink by a factor of 15, adoption of this approach would give 'dial up' inks.

Plenary Speakers:

Professor Ijeoma F. Uchegbu - Chair in Pharmaceutical Nanoscience, School of Pharmacy, University College London - learn about Professor Uchegbu - research summary and biography
Dr Véronique Schmitt - CNRS Centre de Recherche Paul Pascal, Bordeaux - learn about Dr Schmitt - some of Dr Schmitt's latest publications - PubFacts
Dr Valeria Garbin - Department of Chemical Engineering, Imperial College London - learn about Dr Garbin's research - research overview
Professor Ricky Wildman - Centre for Additive Manufacture, University of Nottingham - learn about Professor Wildman - research summary

Themes:

1. Novel Characterisation of Formulations
2. Innovative Coatings and Films including Functional Surfaces, Wetting and Surface Texture
3. New Developments in Emulsions and Suspensions
4. Formulation of Biologics
5. Formulation of Nanomaterials
6. Progess in Formulation of Pharmaceuticals
7. Modern Powder Formulation
8. Processing and Scale-up

Organising Committee
Dr Flor Siperstein - The University of Manchester
Dr Helen Ryder - The University of Manchester
Professor Simon Gibbon - AkzoNobel R&D / RSC FSTG

International Scientific Advisory Board
Petra Allef, Evonik
Alain Durand, SCF-Groupe Formulation, Univeristy of Lorraine
Ulla Elofsson, RISE Research Institutes of Sweden
Karin Persson, RISE Research Institutes of Sweden
Jordi Esquena, IQAC-CSIC / GECI
Malcolm Faers, Bayer
Andreas Forster, Dechema
Sirnon Gibbon, FSTG-RSC / AkzoNobel R&D
Cecile Pagnoux, SCF/ University of Limoges / ENSCI-CNRS
Frank Runge. BASF
Bernd Sachweh, BASF
Flor Siperstein, FSTG-RSC / The University of Manchester
Gordon Tiddy, The University of Manchester / RSC

Local Organising Committee
Richard Bryce - The University of Manchester
Rosa Cuellar Franca - The University of Manchester
Claudio Pereira da Fonte - The University of Manchester
Alain Pluen - The University of Manchester
Thomas Rodgers - The University of Manchester
Helen Ryder - The University of Manchester