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By Jim Bullock, May 2016

As a humble scientist in a new job (too) many years ago, one of my earliest introductions to the daunting world of chemical engineering was my first encounter with a spray dryer. As I was shown around a scale-up lab I was introduced to the technician running the pilot scale spray dryer – a fairly big piece of kit about the same height as (but a lot wider than) an adult human. At that moment I was surprised to see the technician apparently assault the spray dryer violently with a crude weapon of his own devising – a short length of flexible rubber hose wrapped in duct tape. Mildly alarmed, I learned a little later that this wasn’t his way of venting his frustration, but actually a fairly practical way of removing build-up of material from the sides of the dryer. All of which taught me that there is a difference between the laboratory world of delicate glassware and the practical world of large chemical processing equipment – and that scaling up processes brings with it a new set of challenges and considerations.

At that time I saw spray drying as simply a standard processing step, a way of taking a liquid product and making a dry powder from it. Useful, but not much more. Then one day our lab in the speciality chemicals division of the company was visited by a young scientist from the (much more profitable, cutting edge and richer) pharmaceutical division. She had come to use our small scale lab spray dryer (which was made of glass and definitely not something to be attacked) for some experiments. As we were a bit surprised that our expensive pharma colleagues didn’t have their own spray dryer, we asked her why she had to use ours and got the reply “because we don’t really know anything about spray drying”.

The latter experience was an important indication to me that technologies which are completely established in one industry can be completely novel to another industry, and that this disparity has nothing to do with how well the industries are funded or how good its scientists and engineers are. So when we fast forward to the present day and the recently held University of Leeds course “Spray Drying and Atomisation of Formulations” (supported by iFormulate) it was rewarding to see plenty of innovation on show. Over time, the pharmaceutical industry has well and truly adopted spray drying as a technique for precisely designing and engineering small particles, especially for delivery of active ingredients in inhaled dosage products. So it turns out that all those years ago I didn’t “really know anything about spray drying” either. At the course it was also good to see delegates from industries as diverse as food, catalysts, agrochemicals, explosives and pharmaceuticals benefiting from an understanding of the common science and engineering principles and practicalities – and exchanging ideas that crossed those industry boundaries.

If you missed our recent short webinar on Spray Drying (featuring Professor David York from the University of Leeds) then you can still view the recording via our website. Finally, if you are interested in finding out more about the benefits of cross-industry innovation and exchange of ideas, take a look at our new White Paper “Open Innovation Across Sectors”.

By David Calvert, May 2016

As the football Premier League in England came to a conclusion, I asked myself the question “what system would be considered the “Leicester City” of formulation design?”. To most of those in the pharmaceutical industry, then Quality by Design (QbD) is considered best practice. One of the main drivers for QbD was to try and minimise the time taken to get a dossier through the regulatory process and I was interested therefore in a  presentation at the recent QbD symposium organised by De Montfort University (based by chance in the very same “Premier City”).

In his presentation, Colm Reddington of the MHRA (the UK medicines regulator) examined 69 applications made to the Chemistry, Pharmacy and Standards (CPS) expert advisory group which advises the Commission on Human Medicines (CHM) on matters relating to a range of quality issues. He classified the applications by the extent to which they demonstrated enhanced Quality by Design approaches. The applications were ranked with those at the lower having a mainly empirical approach and those at the top which had established a design space and used process analytical tools (PAT) amongst other QbD techniques. Interestingly around half of the applications were considered to still use the traditional empirical approach but around 20% were towards the higher end of the spectrum. During the examination process, the majority of the major objections came where the empirical approach was taken with only one major objection in the top two categories.

Whilst the sample size was small, it does offer some proof towards the logical conclusion that a good design will lead to a better defined product. Even in this study though it is worth considering if a full blown QbD approach is always the best approach. In our training course on “Design for Formulation” which we ran last year, Ian Jolliffe and our other speakers demonstrated how a structured approach to the formulation design process is the best one, but that this must be tailored towards each specific industry – and a risk management approach is key. You can view a webinar recording of Ian discussing what you need to do before you go in the lab on our web-site  and Ian’s forthcoming webinar “iFormulate introduces Powderology – An Introduction to the Mysteries of Powders”, you will also hear how this approach can be key in working with powders in all types of formulations. You can register for this on the webinar page.

By David Calvert, March 2016

Having attended the Making Cosmetics Exhibition recently at the Ricoh Arena in Coventry I thought I would share my observations on what seem to be the key issues in this industry and what makes it different, or not, to other formulating industries.

As you would expect from this consumer retail driven market, there is a great emphasis on the brand and how to develop it. As well as the exhibition, there was an extensive seminar programme (too many to attend in my short time there) with a number of presentations looking at realising ideas, developing and enhancing brands and how to identify what retailers are looking for in a  successful brands. Branding is of course a key element in a number of other formulating markets such as FMCG, coatings, healthcare  and even pharma to some degree, but I have the impression that in cosmetics it is of utmost importance.

Of course a good brand is based on good claims and a number of presentations looked at testing and substantiating these claims. This topic is a key element of the forthcoming SCS Annual Conference “Science in a Bottle” in May. What perhaps impressed me at the exhibition were the large number of portable devices which were being demonstrated allowing in-particular measurements of skin properties to be taken quickly and non-invasively at the consumer. Maybe this “off-site” measurement is a trend that we will see spreading into other industries.

Clearly, product claims are based on the ingredients themselves and not surprisingly there were a number of new ingredients which were natural or bio-based and could claim to be clean ingredients. Away from the exhibition I was intrigued by a recent e-mail I received from DuPont Tate and Lyle promoting their new Zemea® propanediol for cosmetics as an alternative to petroleum-based glycols. Looks interesting and wonder if it will be taken up by the formulators.

Of course ingredients need to be combined or formulated into the products and as you would infer from the name of the exhibition there were a number of processing and contract manufacturing companies exhibiting. The processing companies were familiar ones from other markets with Silverson, Netzsch, IKA and the ever expanding Ytron Group exhibiting. I must admit I did not see that the equipment differed too much from that used in other industries with mixing, suspending, dissolving and aerating being common unit operations for all formulators.

Cleaning is also a common operation but I was struck by both Doronwell and Ecolab exhibiting and making presentations on their cleaning solutions. This has spread from the food industry and the need for CIP in the pharma industry but increased emphasis could be down to the expanding number of ingredients in cosmetic formulations and also some extra scrutiny on sweating assets and looking for less down time due to cleaning. I recently listened in on a webinar from Croda on industrial cleaning where they outlined the use of HLB to match cleaning solution with the product needing to be cleaned. Although this may seem old science to some, it appears to have been effective and the offers on show at Making Cosmetics were also clearly built around good science.

Two final observations, good to see the National Formulation Centre talking about their programme and interesting that Chemspeed were exhibiting and talking about automation of processes for faster product development in cosmetics. Again, a trend we have seen in other formulating industries.

The next “sister” exhibition is “Making Pharmaceuticals” on 26-27 April in Birmingham. We will be there on the 26^th running a workshop on Open Innovation with our Associate Partner, Malcolm McKechnie. Please come along if you are going to the exhibition. If you are unable to make it but are interested in Open Innovation, then you can download our White Paper on Open innovation from our web-site.

By Jim Bullock, March 2016

It’s a natural human tendency to divide people into heroes or villains, and things into good or bad. Reality is more nuanced than that as I was reminded of recently when I learned a little about the illustrious 20^th century crystallographer J.D.Bernal. Bernal studied under Nobel prize winner William Bragg and two of his own students, Dorothy Hodgkin and Max Perutz, also won Nobel prizes, with Perutz’s student Francis Crick also picking up the prize of course for his part in solving the double helix structure of DNA. Bernal’s work helped to lay the foundations of the modern science of “crystal engineering”, the deliberate design of specific crystal structures in order to create solid materials with desired application properties. The science has moved on in recent years and the many applications for crystal engineering now include more effective medicines, as well as using metal organic frameworks, which are “cage” or “sponge” structures which have the potential to carry out energy-efficient chemical separation or to mop up and capture that 21^st century villain, carbon dioxide [1]. Except that carbon dioxide isn’t always a villain of course. This week I also caught up with progress in developing methods which use supercritical carbon dioxide in carefully controlled crystallisation processes. Supercritical CO₂ is used as an antisolvent to produce highly uniform engineered crystals from pharmaceutical active ingredients. The process can lead to medicines which are more effective, quicker acting and easier to take than conventionally produced formulations [2]. So sometimes, CO₂ can be a bit of a hero as well.

Crystal engineering works best if you can predict the crystal structure of the organic sold which you are designing. In 1994, Angelo Gavezzotti tried to answer the question “are crystal structures predictable?” and was tempted to write a one word scientific paper (“no”) in response [3]. Fortunately science, moves forward and the regular “blind test” challenge in crystal structure prediction (led by the Cambridge Crystallographic Data Centre [4]) has stimulated developments in modelling and simulation. Judging by Dr John Kendrick’s recent comments [5] the answer to Gavezzotti’s question is now “often yes, sometimes no”, which I think counts as progress.

So scientific opinions change, as do political ones. And what of Bernal? In common with many of his time, he was a committed communist and was awarded the Stalin Peace Prize in 1953, an award which turned a scientific hero into a political villain to those who didn’t sympathise with Bernal’s politics. But this story of heroes and villains doesn’t stop there. Bernal’s Nobel-winning student Dorothy Hodgkin shared many of his political views and later, in one of those interesting twists of fate, one of Hodgkin’s own students was none other than a certain Margaret Roberts. Roberts was later known as Margaret Thatcher of course and as a famous enemy of communism you’d have thought that she would have seen Hodgkin as a villain. On the contrary, the Iron Lady respected Hodgkin’s scientific prowess and reputedly remained on good terms with her after becoming Prime Minister – even seeking her advice on the Soviet Union.

At iFormulate we won’t advise you on politics but we do offer consultancy services in technology scouting and profiling in the area of formulation science and technology. We use our extensive industrial and academic network to stay up to date with developments of industrial relevance. Contact us at info@iformulate.biz if you think you have a challenge for us.

(Image credit: Dooris E, McAnally CA, Cussen EJ, Kennedy AR, Fletcher AJ. A Family of Nitrogen-Enriched Metal Organic Frameworks with CCS Potential. Crystals. 2016; 6(1):14. reproduced under Creative Commons Attribution License)

[1] Professor Michael Zaworotko “Crystal Engineering: From Form to Function” at “Fundamentals of the Solid Form”, March 2016: https://www.formulation.org.uk/sf16home.html

[2] Professor Peter York “Designed particles for optimised formulations using supercritical fluid technologies” at “Fundamentals of the Solid Form”, March 2016: https://www.formulation.org.uk/sf16home.html

[3] Angelo Gavezzotti “Are Crystal Structures Predictable” Acc. Chem. Res., 1994, 27 (10), pp 309–314 https://pubs.acs.org/doi/abs/10.1021/ar00046a004

[4] Sixth Blind Test of Organic Crystal Structure Prediction Methods: https://www.ccdc.cam.ac.uk/Community/initiatives/cspblindtests/

[5] Dr John Kendrick, Elizabeth Colbourn Memorial Lecture at “Fundamentals of the Solid Form”, March 2016: https://www.formulation.org.uk/sf16home.html

If you’ve ever considered looking outside your own organisation for new ideas to boost your R&D, or if you’ve thought about collaborative innovation activities then you’ve probably come across the principles of Open Innovation (OI). External partnerships can really help bring in new ideas, opportunities, technologies and understanding into your organisation. But what are the best ways of engaging in OI, what are the common pitfalls and how do you avoid them?

Well, together with iFormulate’s Associate Partner, Malcolm McKechnie, we’ve written a White Paper which shows how you can gain maximum value from Open Innovation by taking a look outside your own sector in order to find new opportunities, new technologies and new partnerships. Formulation is a great area to take this approach because companies in pharmaceuticals, cosmetics, homecare, foods, agrochemicals, paints and inks are often faced with similar challenges and can make use of a common set of technologies.

To receive a copy of the iFormulate White Paper “Open Innovation Across Sectors for Pharma, Health and FMCG” then simply email us at info@iformulate.biz.

By David Calvert

As commentators discuss the innovation process and cite the most successful, and profitable, examples of innovation they may mention a disruptive technology which changed an entire market. One example we all recognise from our daily lives would be digital photography and how this completely changed the way we looked at preserving our memories.

Often though, innovation is driven by a regulatory change. For example, in the 1980s we saw the Montreal Protocol leading to a ban on the use of Chlorofluorocarbons (CFCs) due their causing thinning of the ozone layer. This ban led to innovation as more benign chemicals were introduced. An interesting and unforeseen potential benefit has been recently claimed – the CFC ban may also have caused a pause in global warming.

Moving closer to home for product formulators, there has been a recent regulatory move in the USA which is leading to some forced innovation. At the end of last year President Obama signed  the “Microbead-Free Waters Act of 2015” which will ban the manufacture of the plastics from 2017 and will be followed by further product-specific manufacturing and sales bans in the following years. The pressure on these products does not show a sign of stopping and further bans in the EU and other regions appear likely.

The microbeads in question are used in a variety of products such as cleansers, scrubs, body washes and toothpastes – so the market for sustainable alternatives is significant. Bamboo powder, rice, apricot seeds, walnut shells, powdered pecan shells are now being promoted as natural options. The fact that a large number of major companies are now committed to stop using microbeads in their products will no doubt lead to some further innovations and there is no reason to assume that these solution won’t be synthetic as well as naturally derived.

When you’re faced with an external change which forces a change, you may look for innovations from outside of your own market. The process of “Open Innovation” and engaging with partners outside your own company and industry can present some challenges, but in a recent webinar and brochure we demonstrate how to make it work and stimulate innovation. We have also published a white paper on this subject and this can be obtained by sending an e-mail to info@iformulate.biz . So if you are in need of a “cleaned up innovation”, then please get in touch!

February 2016

As 2015 draws to a close we thought we would share some of our “video highlights” in the form of recordings of our free webinar series which we launched this year. Follow the links below to view the recordings.

First up, Dr. Ian Jolliffe introduced us to the subject of “Design for Formulation”.

Then Prof. Ian Scowen focused on aspects of “Formulating Particles in Suspensions”.

Finally Dr. Malcolm McKechnie took us through the subject of “Open Innovation Across Sectors”.

If you’ve enjoyed one or more of our webinars this year, or if they are new to you, then keep an eye out for the next one in our series. This will be “Crystallisation Science and Agrochemical Formulation” (sponsored by Technobis Crystallisation Systems). It will take place on 4th February 2016 and we will publish registration details shortly – so watch this space.

As ever, contact info@iformulate.biz if there’s anything you’d like to discuss with us.

December 2015

For the thrill seekers among you the sinking feeling that you experience on a roller coaster – when your stomach is suddenly very light due to less force being exerted on it – is a pleasurable one. For a formulator of suspensions though, that “sinking feeling” is not a good one as you come in to the lab one morning to find that your particles have well and truly sunk. The option of “just shake them up” is often unacceptable to your customers, so what do you do?

Our popular “Suspensionology” one-day training course – being run in partnership with the University of Lincoln on June 17^th – will provide you with many of the answers to your problems and will also give you some of the theoretical background to understand what is happening in your formulation.

One of the pioneers in the theory that describes suspensions was Sir George Gabriel Stokes (1819-1903) who made numerous contributions to the advancement of science in fluid dynamics, optics and mathematical physics. His well known “Stokes’ Law” gave the first insight into the factors influencing the stability of solids in fluids and the principles still apply today. His law states that the velocity of sedimentation increases proportionally with the square of the particle size – i.e larger particles sink more quickly than smaller ones – and also that particles will sink more quickly in lower viscosity media. Despite some restrictions since his work was first published, these findings are still valid today. As well as helping formulators with their products, Stokes’ law also explains why small water droplets can remain suspended in air (as clouds) until they reach a critical size and start falling as rain – or as snow and hail of course!

It is not well known that Stokes was, like all scientists, a true romantic. In a letter to his fiancée Stokes spoke of his plans for the honeymoon and wrote”:

“If we are married at the time we are at present thinking of, and go to Switzerland as we talked of, I think I will bring a couple of quartz prisms, a quartz lens, and a piece of uranium glass with me, to observe the spectrum on top of the Rigi or Faulhorn!”

The good news is that you don’t need to bring any prisms along to the Suspensionology training course in Lincoln, but you can bring along your problems as there will be ample time during the programme to ask questions and gain some valuable insights into the science behind suspensions, as well as a large number of practical tips.

For full details of  Suspensionology and how to register, see the course web page.

David Calvert, March 2015

Attribution: This item is taken from the KTN Newsletter of December 16th, 2014

In the 2014 Autumn Statement, Chancellor of the Exchequer George Osborne announced the funding of a £28m National Formulation Centre, which the Knowledge Transfer Network (KTN) has been instrumental in developing.

The new £28m Centre, to be based at CPI in Sedgefield, will form a hub and spoke model bringing together an existing strong knowledge base of the UK. The spokes of the new centre will include universities, innovation centres and will provide facilities and expertise to help companies to develop, prove, prototype and scale up formulated products and processes.

Complex formulated products are abundant in everyday and industrial life; examples include perfumes, medicines, cosmetic creams, washing powder, processed foods, paints, adhesives, lubricants, composite materials and pesticides and underpin many sectors in the UK economy. The new centre will focus specifically on the areas of product and process design, delivery, stability and sustainability as identified by UK industry in a 2013 consultation report.

The UK formulation industry is underpinned by a strong academic and industrial infrastructure involving particle design and colloid science, modelling and simulation, bespoke measurement and high-throughput automation. The centre will build on CPI’s existing expertise in both formulated product and process design, and will collaborate closely with universities and companies to create a strong route to commercialisation.

There is an existing strong UK knowledge base in formulation but it is fragmented, disconnected and is notoriously difficult to navigate. The KTN will work with the new national innovation centre to help lever, connect and build on these activities to the benefit of the UK supply chain.

Formulation has been a priority area for the KTN after being charged by Innovate UK to identify ways to support UK innovation and growth through investment in formulation. This led the KTN to define an Innovate UK Collaborative R&D competition on ‘Formulated Products: Meeting the Product and Process Design Challenges’ in 2013, and help broker partnerships between members, which subsequently resulted in a public investment of £9.2m.

The success of the Formulated Products competition demonstrated the industry appetite in formulation and added weight to the process of preparing a model and business case for a National Formulation Centre. The KTN engaged industry from multiple sectors, and of various sizes, to align the centre to their needs and with the existing academic and knowledge base.

The KTN worked closely with BIS, CPI, Innovate UK, the HVM Catapult, and the Chemistry Growth Partnership, to maximise the chances of success, through strong lobbying and strengthening of the business case, and is delighted with the announcement that the centre is now to be funded.

For more information and to discuss further, please contact Darren Ragheb, NFC Project Lead at CPI: Darren.Ragheb@uk-cpi.com.

Image: Serge Bertasius Photography at freedigitalphotos.net

By Dr Ian Jolliffe, iFormulate Associate Partner, December 2014

A fascination with the way things are put together, a pharmacy degree and inspiring leadership in pharmaceutics led me to a career in formulation. There are some amazing materials available to use in formulations, both synthetic and natural. The diverse functionality of natural ingredients, especially polymers, is stunning.  That functionality can be physical functionality as seen in the formation and strength of spider’s webs; stalks to hold up the fronds of seaweed to allow them to capture the sun’s energy or actual biological action such as the healing properties of hyaluronic acid. How do we formulate these materials to exploit these functional properties? There are so many exciting challenges and opportunities like these. It’s up to formulators to take these materials and use these to support the generation of ideas and innovative products and then work out how best to turn them into products that can be successfully realised commercially.

An understanding of particle and materials properties is essential for a formulation. I discovered  what strange materials powders were during my PhD and this has haunted me since. For instance, at breakfast time there is muesli; how unfair it is that my wife pours out a bowl of fruit and nuts but the bowl I pour for myself consists mainly of boring oat and wheat flakes! Of course this is due to segregation and separation during product mixing, storage and pouring. This behaviour is typical of many things that we formulate. For example, if we make a powder product for treating colds that has to be reconstituted in hot water, how would it be if some of the sachets get all the drug while other sachets contain little drug and mainly  fillers?

Segregation in bulk powders and other collections of particulates can be assessed at the early stages of formulation design and segregation behaviour is an important parameter when justifying the choice of a specific grade of an ingredient.  Often visual inspection (as in the case of my muesli) will if tell you if gross segregation is occurring at the early stages of formulation design. Eventually an analytical evaluation is required to detect the fine detail of the extent of segregation or if particles of different composition cannot be readily distinguished . This is especially true for critical products such as medicines.

If you haven’t tried it, you may find that the sampling of powders is fraught with difficulties. Just putting a scoop into the powder bed will induce differential flow of particles and the development of slip planes which can cause segregation at the sample point and result in a non-representative sample. For an illustration we can go back to my breakfast – if I put a spoon into a tilted box of muesli I will find it filling up with larger particles which have a higher propensity to roll – hazel nuts being an obvious example. Today more in-situ analytical techniques may be used to remove the need for sampling but it is still important to ensure that the detection point does not induce segregation.

So, how do you prevent segregation? Careful selection of material grades so that the physical properties of particles of the different components match each other as far as possible can reduce the propensity to segregate. In this case the particle size, the shape and the density are typical parameters to be assessed. These can be tricky to determine, for instance in the case of particle size what is the diameter of an irregularly shaped particle? In the case of shape, what shape factor should be used? How can you change density – perhaps by changing the particle porosity? Should you also consider differences in the surface frictional properties, surface charge  and surface moisture.

The most robust formulations are the ones that stay homogeneous through processing, dosing into consumer units, storage, transport and consumer use. So we do the best with the materials we have and if we need to we can use process techniques such as agglomeration or milling to achieve a more uniform size and shape. One popular manufacturer of muesli seems to adopt the latter approach has milled up of all the components together. So I guess that consumers consider the benefit of  having a consistent mixture of  ingredients throughout the packet  is more important that experiencing the varied texture of conventional muesli, the composition of which may vary between the bowls of different members of the family!