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By David Calvert, June 2024

In our last post in this “Design for Formulation” series we discussed what should be done before you go into the laboratory, highlighting technical briefs and sources of previous knowledge. We ended by saying that a preliminary risk assessment should be carried out and here we briefly give an example.

Let’s take a look at a simple gel-based herbicide for consumer use. It has four components, the active ingredient, an adjuvant, a gelling agent (rheology modifier) and water. For the purposes of this example, the customer promise includes the statement “Will work in one application and 100% of the gel is applied to the weed.”.

From this we established that two of the critical quality attributes were the amount and quality of active applied in one dose and that all of the applied product must stay on the weed. An initial risk assessment would establish the role each of the four ingredients would play in delivering the critical quality attribute. The effect/risk would be simply graded “high”, “medium” or “low”.

For the critical quality attribute “Will work in one go”, we assessed that the active ingredient, adjuvant and water were all “high”, whereas the gelling agent would be “low”. What this means is that if something was wrong with the active ingredient or adjuvant, then the “risk” of not delivering on the customer promise was high. The water was deemed as “high” as it is known that the hardness of water can sometimes impact negatively on performance of some actives in herbicides.

For the critical quality attribute “Doesn’t flow off leaf” then we assessed that the gelling agent is deemed “high”, the adjuvant is “medium” and water and active are both “low”. The reason that the gelling agent is “high” is obvious as the primary function of including this is to establish the correct rheology profile. The reason behind the adjuvant being medium is that sometimes these may be a surfactant and that these can help/hinder with structure formation.

So, this preliminary risk assessment highlights the areas to investigate initially with the aim of establishing more quantitative detail on for example impurities in the active ingredient and ranges for acceptable levels of the active and gelling agent. They also serve as troubleshooting guides if in the future there are any issues with efficacy or rheology.

A similar risk assessment would be used to look at process parameters, which in this hypothetical case could be “dispensing”, “Blending”, “Addition of Gelling Agent” and “Packing/Filling”. In our assessment we deemed Dispensing and Addition of Gelling Agent to be high risk relating to “Will work in one go” and “Addition of Gelling Agent” to be high risk for “Doesn’t Flow off Leaf”.

Often risk assessments are presented in a tabular format and these are shown below:

So now we are ready to get to work and in the next post we will look at various approaches to designing experiments.

By Dr David Calvert, iFormulate Ltd, April 2024

For the full article, see  AgroPages 2024 Formulation & Adjuvant Technology magazine and website pages.

Whilst there are many definitions of formulation science, one which is most applicable is “a  technology used to deliver an active ingredient safely and effectively to the right place at the right time″. Looking at this closely it is obvious that this applies to a large number of applications such as pharmaceuticals, inks, coatings, homecare, food, drink, cosmetics and of course agrochemicals. A skilled formulator will often look outside their own industry for solutions and in this article, we examine examples and opportunities where the agrochemical formulator could learn from other sectors.

To read the rest of this article go to AgroPages 2024 Formulation & Adjuvant Technology.

By David Calvert, April 2024

Previously we made the case for a structured approach to “Design for Formulation” and looked at some of the important terms used in the process. Now we look at the important phase of work before you even go in the lab. We mentioned business and technical briefs previously but as these are the formal basis of deliverables and verification of success it is worth some time discussing their content.

It needs to be stated is that these should never be done in isolation by the technical team and that sales, marketing, regulatory and production should be involved. The business brief makes the business case for the project to go forward and would include elements such as market size, projected sales price and margins, competitive landscape, target customers, regions, resource requirements and sales projections. Once the business case has been accepted then the technical team can lead the definition of the technical brief.

From the Customer Promise, claims will be made and included in the technical brief. What is the shelf life and under what environments? What regulations apply to the product and the region where it is to be manufactured and sold? Based on margins and price, are there defined cost targets? Are there any manufacturing requirements/restraints? What type of packing/dosage mechanism is envisaged? Is there a competitive benchmark? What are the performance targets leading from this and are there any new tests that need to be developed? There will be many more elements in the final technical brief which should be quantified as far as possible and signed off by all.

At this stage it is then easy to rush off and start some work in the lab but the first thing you should do is… nothing! Well not quite, but you should start to look at what prior knowledge you have regarding the project. This will be internal looking at previous similar projects, considering what is different and how previous challenges were met. There will of course be internal experts and it is important to take these into account whilst still remembering that a previous project may have not been successful due to lack of materials, or different market conditions for example.

As mentioned in the technical brief, it may be worth looking at competitor products, literature and any patents. The latter can of course provide valuable background but also avoid potential infringement. Further external resource is obviously available from the internet and you may even want to ask some questions of artificial intelligence engines but as we have stated before you need to consider the quality of this information. The final source of the external information is from consultants and of course if you are looking for formulation consultants, then contact us and we may be able to help!

So now you can finally get on with some practical work? Well, not quite – and in the next article we will walk you through an example of a preliminary risk assessment.

By David Calvert, 19th March 2024

We have previously made the case for a structured approach to “Design for Formulation” and in this post we look at some of the important terms used in the process.

The whole process starts with a “Customer Promise”, namely what your customer expects from the product and what you promise to deliver. It may seem blindingly obvious, but we have seen in many instances that, when pressed, companies find it difficult to express in a succinct way what they are going to deliver. Developments are often driven by an internal technology development or a vague perception of what the market needs. At its best the customer promise can be expressed in one, maybe two sentences.

From the “Customer Promise”, business and technical briefs will be developed. We will say  more about those in the next article but these lead to definitions of what are the “Product Quality Attributes”. These are the properties of the final product that can be measured to determine that the product delivers on the “Customer Promise”. From these you start to define “Raw Material Attributes”, which are the properties of the raw material which are required to deliver the “Product Quality Attributes”. It is important to note that these are not necessarily measures you find on the raw material specification. As an example, the specification for the particle size of a powder may include a value for the D50, but you may find that the D10 or D90 are more relevant measures and could discuss this with your supplier.

The full list of these attributes may seem long and daunting and it is here that the “Risk Assessment” exercise is invaluable. This is not the typical risk assessment to decide whether a chemical is safe to use in the laboratory or in manufacturing but is an assessment of the consequences of what would happen to the product, and your promise, if you did not achieve the specific product or raw material attribute. Initially this assessment is based on “Prior Knowledge” (more of this in the next article) but as the process continues it is based on experimental or process data generated. By carrying out the risk assessment exercise, you develop an understanding of what is believed to be “Critical” and in your experiments you focus on quantifying this risk.

A similar exercise covers your formulation and manufacturing process and understanding the “Critical Process Parameters” which we will also cover in a future article.

In the next article, we will outline the five stages in the Design for Formulation process with a focus on the first stage “Getting Started” which is carried out before you even go into the lab. 

By David Calvert 7th March 2024

The topic of AI and systems such as ChatGPT is much discussed and opinions on the validity and value of these approaches varies widely. At iFormulate, Jim Bullock recently gave a video presentation on how AI, Machine Learning (ML) and automation are being used in formulation development and we have even investigated ChatGPT .

A recent article in ChemEurope piqued our interest further when it discussed how to measure the actual value that AI-driven chemistry labs actually deliver by establishing some common metrics. Whilst the article focusses on researchers and chemistry, we think this has significant applicability to those working in the formulation space. The target of “producing trustworthy, reproducible results that make the most of AI programs that capitalize on the large, high-quality data sets produced by self-driving labs” made us reflect on some work we carried out a few years back on open data and how this could be applied to formulations. Whilst there was enthusiasm for using and compiling formulation data from a number of sources, there was considerable concern around quality of data used, and in particular how realistic it was to expect all research to use standardised test methods. Even for something as seemingly “straightforward” as particle size measurement, how could an open data set deal with different techniques? A measure for “stability”, which is still our most common consultancy request, presents more questions than answers.

We do not wish to be viewed as holding back new technology and becoming “luddites” with regard to AI. There are clear signs that using AI for internal data which is well controlled can bring significant benefits. Croda recently published an article how they are using AI to not only improve their formulation development but also reduce carbon footprint and assess business risk. There will no doubt be other examples of applying digital technologies to formulation at the RSC event, Formulation 4.0, in July of this year.

We do believe that AI will be a game changer but as with all new technology there must be some critical evaluation and there will still be room for “non-artificial intelligence” in formulation! 

By David Calvert 6th March 2024

At iFormulate, we have long been proponents of a structured, yet flexible, approach to formulation which we have commonly called the “Design for Formulation” approach. This has been embraced by many of our clients and has formed a part of a number of customised training and workshop sessions. During these projects, we have taken clients through the approach with specific reference to their products (frequently with a Non-Disclosure Agreement in place).

Over the next few weeks, we thought it would be of value to go through the process and its different stages. Before delving into these, it is important to make the case for a structured process in the first place and that is the purpose of this first article.

In many mature organisations the development of formulations has taken an organic, evolutionary approach and often when you step back and take an objective view of the process the phrase “if I were you, I wouldn’t start there” can come to mind. Whilst this can lead to a successful development, there can often be issues such as:

·      A late product launch
·      High production costs
·      An unreliable process
·      Batch failures due to formulation not being robust
·      Inability to change manufacturing site or equipment
·      No flexibility in raw material suppliers
·      Loss of expertise and experience  

Whilst there is no guarantee that our preferred development process will eliminate all of these issues, it will minimise the risk of these occurring.

When outlining the process, we aim to remove some of the mystique and perceived bureaucracy of a well-structured approach. It cannot be denied that knowing what you did, why you did it and what the results were is not valuable and can be of significant benefit when starting new projects. Even with developments such as artificial intelligence (AI), there will always be the need for experience and subjecting decisions to some friendly scrutiny.

Through the next few weeks, we will expand on how to maximise benefits from the “Design for Formulation” approach and the next article will look at some of the terminology and how these help to drive the process  

The publication is Open Source (CC-BY 4.0) and can be read and downloaded at the ACS website or viewed below.

Following her M.Chem, which included the experimental project supported by iFormulate, Ana has gone on to complete a PhD at the University of Nottingham.

January 2024

With Professor Steven Abbott

At iFormulate we know that formulation challenges are rarely simple, requiring multiple pieces of science to be brought together. But formulators cannot know every key principle or be expected to do the calculations behind those principles.

So we are delighted that Professor Steven Abbott – a good friend of iFormulate – has produced for the formulation community an extensive “Formulation Scientist’s Toolkit” containing the tools, and links to his many apps that bring the tools to life. Best of all it’s a free and open-source PDF that you can simply download here. Any time you have a problem, you open it and find the tools you need, along with explanations, equations and links to the apps. At the top of this article you can view a video of Steven explaining the Toolkit.

How do you find what you want? The book is built on a matrix of Products and Sciences. You find a Product that’s relevant to your needs, and it contains links to the different Sciences you need to formulate in that space. Click on any of the Science links and you see other Products for which it’s relevant. Now you can get formulation inspiration from other domains. That’s one way to use the FST. You can also use the PDF Search function, or use the Thumbnail bar or Bookmark bar, whatever gets you to the information you need.

Some will use it to find the thing they need right now. Others will choose to get lost in the interconnections between Products and Sciences. Some will spend a lot of time exploring apps. It’s a toolkit, not a book. And it’s your toolkit so you can use it any way you like.

Having taken a look ourselves we think that you will enjoy re-discovering things you’ve forgotten you knew, and learning things you didn’t know that you didn’t know! If the science gets heavy going, Steven lightens things with stories from his own formulation life, including learning from his mistakes.

As Steven freely admits, the FST is imperfect. But it’s been designed to be easy to update. Anyone with a complaint, correction, suggestion can email him and things will be fixed. Steven has also asked our help to identify what should be priorities for new Product and Science chapters, so we welcome your views. As he said to us recently “The more the community helps the FST to grow, the more tools we have for creating better formulations, faster.”

Happy exploring, and it will be great to hear your feedback – please let us know what you think.

iFormulate’s Dr Jim Bullock interviewed for Azo Materials at ChemUK 2023

This year, we were once again pleased to be attending and speaking at ChemUK at the NEC in Birmingham. The event has rapidly established itself as being the premier meeting point for the UK’s chemical industry and its supply chain. This time, I had the pleasure of being interviewed by Skyla Baily of Azo Materials and was able to explain a little about how we work to help our clients with their challenges in formulation. You can find the full interview here.

ChemUK returns to the NEC on 15th and 16th May 2024.

By Dr Jim Bullock, iFormulate Ltd.

For the full article, see  AgroPages 2023 Formulation & Adjuvant Technology magazine and website pages.

In recent years, much attention has been paid to the environmental problems caused by plastic pollution and in particular, by microplastics – small pieces of plastics which may be found in the environment and in the food chain. The EU defines microplastics as being:

″Particles containing solid polymer, to which additives or other substances may have been added, and where at least 1% w/w of particles have all dimensions between 0.1µm and 5mm, or for fibres, a length of between 0.3µm and 15mm and a length to diameter ratio of more than 3.″

After a period of fact-finding and consultation lasting several years, the European Commission published a draft Regulation (amendment to REACH) in 2022. This would place restrictions on microplastics intentionally added at 0.01% or more by weight. Excluded from the restrictions would be natural polymers, biodegradable polymers and polymers with at least 2 g/l solubility in water. ECHA published the draft amendment to the REACH Regulation in August 2022. The proposal is going to the EU Parliament, and it is expected that there will be a transitional period of five years after entry into force for uses of agricultural and horticultural products.

Although much of the microplastic contamination we see in the environment has its origin in packaging materials and car tyres, product formulation plays a role too. These restrictions will be especially relevant for cosmetics, household products and agrochemicals. However, with the elimination of plastic microbeads from cosmetics, the spotlight has moved onto other industries and application areas. So first, let’s take a look at the challenges for formulators of agrochemicals who may be tasked with removing many of the polymer materials used in products such as microencapsulated formulations, seed treatments and slow-release fertilisers…

To read the rest of this article go to AgroPages 2023 Formulation & Adjuvant Technology.