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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.

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!

By Paul Mahon, iFormulate Associate Partner, November 2014

Most of the science needed to predict, control and define the stability of solutions was defined by scientists of the Victorian era such as Ostwald and Arrhenius. Nevertheless, as formulation chemists, we still regularly encounter poor stability in liquid solution products. The reason for this, I believe, is that solubility and stability studies are still sometimes regarded as trivial and so are not properly thought out and executed.

So how do we ensure that our solutions remain stable? Firstly, we need to measure the true solubility of our solutes, then we need to assess the physical and chemical stability of any solutions we make with them.

The solubility of a material is the concentration of the solute in a steady state, saturated solution at any given temperature. The solubility of a solid generally increases with increasing temperature and is often (but not always) greater when the melting point is lower and the latent heat of melting is smaller.

In practice real-world solubility measurements are not usually absolute and many things can influence the apparent solubility, important factors are:

1. Supersaturation: Simply dissolving a solute in solvent, especially if you use agitation, heat or ultrasound will usually create an thermodynamically unstable “supersaturated” solution.

2. Purity: generally speaking the purer the (solute) material is then the lower its solubility will be.

3. Measurement method: The apparent solubility can sometimes vary depending on how you measure it.

4. Polymorphic form: Most solutes will have many different polymorphic (crystal) forms, with widely differing solubilities.

5. Particle size: Very small particles can be much more soluble than larger particles.

6. Nucleation & growth: In the absence of heterogeneous nucleation sites metastable solutions can be indistinguishable from true solutions.

7. Chemical stability: Reactions can occur between the solutes, solvents or environment.

1 Supersaturation:

The supersolubility limit is the concentration at which spontaneous crystallisation occurs in the absence of heterogeneous nuclei. Heterogeneous nuclei can be anything from scratches on the container walls to bits of foreign matter, dust etc.

The metastable region in the diagram below is the area lying between the solubility and supersolubility concentrations. In this area, a crystal will grow but spontaneous nucleation will not occur (over reasonable time periods).

TYPICAL SOLUBILITY PHASE DIAGRAM

In the case above the solute has an equilibrium solubility of 1% at 25⁰C, and 2% at 35⁰C. A clean 2% solution cooled from 35⁰C to 25⁰C will still appear to be stable because there are no crystals to grow. However, the introduction of any nuclei would cause a rapid precipitation of half the material from solution. For this reason we do not normally use heat, ultrasound or high shear when measuring solubilities and we would usually ensure that there are nucleation sites present in the vessel.

2 Purity

High purity materials tend to have lower solubility than slightly impure materials, this is because impurities can get into the crystal lattice causing dislocations which change the chemical potential of the solid – in the same way that impurities lower the melting point. However, different types of impurity can have different effects, some can increase solubility but others can decrease solubility. For this reason if the source, grade or purity of the solute or solvent is changed in any way, the solubility and/or stability of the solute will need re-assessing.

3 Measurement Method

This is particularly important if the solute is a mixture – either by design or because it contains impurities. If we make a supersaturated mixture of solute and solvent and then measure how much is in solution we will be measuring the most soluble components of the mixture. However, if we take clean solvent and add solute to it until we see material out of solution then we would be measuring the least soluble component of the mixture.

4 Polymorphic Form

Polymorphism is all about minimising free energy.

Gibbs free energy equation: 

If ΔG is negative then crystals will always form as this is thermodynamically favoured. What is more difficult to derive is how long this might take, i.e. the kinetics. Almost all organic molecules are known to exist in many different polymorphic forms. By definition, the most stable polymorphic form of any material is the one with the lowest chemical potential. This means that the most stable polymorphic form must always be the least soluble. In practice what this means is that the supplied solute may often be in a more soluble polymorphic form, but it may change to a less soluble form when in solution via a process known as solvent mediated polymorphic phase transformation.

If we measure the wrong (less stable) polymorph we will always get too high a result for our solubility. For this reason we need to convert the solute to its most stable polymorphic form. This can usually be achieved by temperature cycling a saturated solution. The temperature cycling conditions required depend upon the solvent but usually a -10^oC to +40^oC daily cycle for a few days will suffice.

 

5 Particle Size

The same Gibbs free energy equation tells us that solubility is dependent on particle size, i.e. their surface area to volume ratio. It only really makes a difference when the particles are very small – 0.1 micron or less. Again we have the problem that measuring solubility of very small particles will give too high a result, and the solution will be unstable long-term because a process called Ostwald ripening will occur. The small crystals may well dissolve easily, but at some later stage large crystals will grow because they will have lower solubility and the solution will be supersaturated with respect to the larger crystals. For this reason we need to convert sub-micron solutes to larger crystal sizes via Ostwald ripening. This can also usually be achieved by temperature cycling a saturated solution as above.

 

 

6 Nucleation & Growth

Nucleation and growth are thermodynamically distinct processes, with nucleation being the initial formation of a crystallite of a critical size and then growth being the subsequent exponential increase in the crystal size.

Homogeneous vs Heterogeneous Nucleation

Again, this has practical implications for us. Homogeneous nucleation (in the absence of any nucleation sites) usually has a much higher free energy barrier than heterogeneous nucleation. The implication is that if we measure stability or solubility in clean laboratory glassware for instance, then we may be looking at a supersaturated solution. This may act like a true solution until the introduction of foreign nuclei results in sudden catastrophic crystallisation. On an industrial scale there will almost always be foreign bodies or rough surfaces to act as a scaffold for nucleation. For this reason we need to ensure that sufficient nucleation sites are available, this can be from scratching glassware or metal containers or by the intentional introduction of seed crystals.

7 Chemical Stability

Chemical stability refers to the propensity of the solute(s) or solvents to react or decompose in solution. The kinetics of the chemical reactions can be zero, first, or higher order. However, generally speaking, the observed responses for zero and first order reactions are indistinguishable for products that decompose relatively slowly.

Like all chemical reactions the decomposition rate decreases by a constant factor when the temperature is lowered. The relationship between temperature and the decomposition rate has been well characterized by the Arrhenius and related equations:

Given data on concentration vs. time data at two or more different temperatures we can calculate the rate constants for the reactions and the activation energy. This data then allows us to calculate the degree of decomposition at any other time/temperature as long as the following conditions are met:

(a) A zero- or first-order kinetics reaction takes place at each elevated temperature as well as at the real-life storage temperature. Theoretically, the Arrhenius equation does not apply when more than one kind of molecule is involved in reactions. However, if the decomposition rate and temperature are linearly related, the prediction of shelf life can still be approximated reasonably well.

(b) The same model is used to fit the decomposition patterns at each temperature, i.e. the temperature is not raised sufficiently high to enable new reaction paths.

We can therefore usually use short temperature stability studies at elevated temperatures to accurately predict long-term stability at lower temperatures.

References:

(1) Robert T Magari: “Assessing Shelf Life Using Real-Time and Accelerated Stability Tests”: BioPharm International Nov 1, 2003

(2) Geoffrey Anderson and MIlda Scott: “Determination of Product Shelf Life and Activation Energy for Five Drugs of Abuse”: Clin Chem 37/3, 398-402 (1991)

(3) Maria Nicoletti et al “Shelf-life of a 2.5% sodium hypochlorite solution as determined by Arrhenius equation”.   Braz. Dent. Journal vol.20 no.1: 27-31 (2009)

Is your company carrying out Formulation work in Scotland? If so, please get in touch, your country needs you!

On behalf of Scottish Enterprise, iFormulate is carrying out a project to map the industrial formulation capabilities and needs in Scotland. This involves assessing capabilities of companies in Scotland and looking for opportunities where Scottish Enterprise could support these companies as they grow.

If your company is involved in Formulation activities in Scotland, we would very much like to speak to you to understand your existing activities and explore options for this assistance. Please contact info@iformulate.biz and we can give you more details and arrange a time to talk further.

Latest: Download the new Modular Masters brochure here.

The Science Industry Partnership (SIP) is pleased to announce the launch of its new Modular Masters qualification in Formulation Science and Technology. With Government co-investment of up to £500 per individual module, and delivery via a combination of lectures, e-learning, distance learning, practical laboratory sessions and teamwork exercises, these modules will provide an in depth understanding of formulation science and technology and its industrial importance.

The innovative Modular Masters is designed for employers to address the lack of specific and coherent training provision in Formulation Science and Technology. It will provide employees with the highly sought after skills required for scientific, technical and production functions at all levels. Employees can study part time and select individual modules to form a fully accredited Masters qualification or alternatively select individual modules to support their Continuing Professional Development.

Brief documentation on the Modular Masters in Formulation can be found here. Details of the first three modules have now been announced as follows:

• Design Principles for Formulation;
• Characterisation for Formulation;
• Preformulation Studies – Biopharmaceuticals.

iFormulate and Cogent, on behalf of the SIP, are encouraging any employers or prospective students to register their interest on the course as soon as possible. To reserve your place please email HEOperations@cogentskills.com.

For further information on the Modular Masters you can see below a recording of a short information webinar which was held on 12th January 2015.

Information Webinars for Providers 10^th and 13^th October 2014

 

You may have already heard about the Science Industry Partnership (SIP) and the innovative new Modular Masters Programme in Formulation Science and Technology. If not, you will find further details on the SIP website: http://www.scienceindustrypartnership.com/modular-masters/.

The process to select the provider or provider consortium which will deliver the full programme in collaboration with the SIP has now begun. There are opportunities for Higher Education Institutions (HEIs) as well as private sector and other educational providers to become involved. So if you are interested in finding out how you could become part of this exciting new programme then register now for one of our short briefing webinars to be held on Friday 10^th October at 11.00 AM or Monday 13^th October at 12.30 PM.

To register to attend, simply e-mail info@iformulate.biz with your full contact details and preferred webinar date. We will send webinar joining details to registrants ahead of time.

We expect the formal application process to open at the end of October and close at the end of November. Final selection of the provider or provider consortium will be made in early January 2015.

We will also be helping provider consortiums to form by sharing contact details and areas of expertise of interested parties. If you would like your details to be shared in this way, please provide (by e-mail to info@iformulate.biz) a short description of topics, expertise and existing or planned relevant educational provision. If you are considering leading a consortium, you may also wish to indicate in which areas you require partners to fill any gaps in provision.

We look forward to speaking with you at one of the webinars.

By Dr. John Duffy, Product Marketing Manager, Rheology, Malvern Instruments, September 2014

Achieving product stability is a critical aspect of ink formulation. Modern inks are typically colloidal suspensions of multiple components in an organic or aqueous continuous phase. The functionality of the finished product relies on maintaining suspended ingredients in a dispersed state, for the life time of the ink, under all the conditions that will be encountered.

Controlling the size of pigment particles is especially critical. Particle size influences the way in which light interacts with a particle and consequently affects the hue or tint of the finished print. Particle size and size distribution may also impact other important features such as print transparency, level of gloss, weather resistance and stability.

Clearly ink ingredients can be added to a formulation as particles of a defined size. The more difficult issue is how to maintain that particle size once all the ingredients of the ink are combined. Stability studies are often not only one of the most important aspects of ink formulation but also one of the most time-consuming.

Understanding the mechanisms of stability

The factors that contribute to the stability of a suspension may be classified as either kinetic or thermodynamic in origin:

– Kinetic stability is associated with particle motion. Increasing the viscosity of a suspending medium slows down particle movement thereby reducing the likelihood of aggregation and sedimentation. Increasing viscosity therefore increases kinetic stability.

– Thermodynamic stability, on the other hand, is related to steric and electrostatic effects. Generally speaking thermodynamic stability is induced by encouraging particle repulsion, either through size or shape modification, or by altering electrostatic charge. However, in certain systems it is possible to increase thermodynamic stability by encouraging particle attraction and the formation of a stable network structure¹.

Many inks contain suspended particles in the sub-micron region. For such small particles Brownian motion is usually significant in maintaining the dispersion. However, as particles become larger the effect of gravity becomes more significant. Gravitational forces will also dominate if there is a significant difference between the density of the dispersed and continuous phase. This is often the case with pigment particles which can be extremely dense, relative to the solvent.

The ratio of gravitational to Brownian forces directly correlates with the likelihood of sedimentation, a defining feature of instability, which can be predicted from equation 1.

[where a is the particle radius, Δρ is the density difference between the dispersed and continuous phases, g is acceleration due to gravity, k_B is the Boltzmann constant and T is the temperature.]

This equation is very helpful for determining a strategy for improving the stability of an ink:

– If the value of the ratio represented by equation 1 is greater than unity then some degree of sedimentation can be expected. This suggests that kinetic stabilisation is required.

– A ratio of less than one is indicative of a stable system. However, any potential for flocculation/aggregation risks an increase in a, the particle size, and a swing towards kinetic instability. A ratio of less than one therefore puts the focus on safeguarding thermodynamic stability.

The power of three

This rationalization of stability highlights three properties of an ink formulation that can be manipulated to control ink stability:

– particle size of the dispersed phase

– viscosity of the continuous phase or the suspension

– zeta potential of the system

These parameters are inter-related and cannot be manipulated in isolation. For example, changing particle size will impact the viscosity of the overall suspension. Furthermore these parameters influence not just stability but also other aspects of ink performance such as jet-ability (which is related to suspension viscosity) and finish (particle size). Achieving the desired stability is therefore a complex optimization challenge ring fenced by multiple constraints.

An efficient analytical strategy helps formulators to tackle this challenge in a systematic and effective way. In combination, particle size analysis, rheological characterization and zeta potential measurement provide a foundation for such a strategy.

Particle size analysis: Particle size measurements are helpful during the production of ingredients for an ink, during milling for example, as well as supporting stability studies. The particle size range of ink components spans the nanometer/micrometer range and can be met through the application of laser diffraction particle size analysis or dynamic light scattering (DLS) techniques. A modern laser diffraction analyzer will robustly measure from the 0.01 to 3500 µm while DLS instruments offer measurement in the 1 nm to 1 micron range.

Rheological characterization: Simple viscosity measurements will support stabilization studies but more broadly rheological studies can help with a number of other aspects of ink formulation. For example, rheological data support the formulation of inks that jet and break up into droplets in a precisely defined way, under the shear conditions applied by a specific nozzle design. Equally importantly, rheological measurements enable a formulator to engineer shear thinning behaviour. An ink that shear thins jets easily but then becomes more viscous when deposited on the substrate, resisting dripping.

Accessing relevant rheological information relies on measuring under the conditions that will be applied during product use. Low shear measurements are most relevant for stability studies, while high shear data more closely reflect behaviour in a jet or nozzle. State of the art rotational rheometers enable the application of different test strategies over a very wide range of shear stress/strain and are routinely applied in ink formulation. However, there are relatively new complementary techniques that usefully extend rheological measurements into areas not accessible with rotational rheometry.

Microrheology, for example, supports the rheological characterization of low viscosity, weakly-structured complex fluids at very high frequencies. It provides detailed insight into the viscoelastic response of a complex fluid, which for inks can be valuable for evaluating jet-ability. Microfluidic rheometry, on the other hand, is an efficient method for measuring viscosity in the ultra high shear region. Again such data is highly relevant to performance at the print head

Measuring zeta potential: In an electrically charged suspension, particles will only approach one another, and cohere, if they have sufficient energy to overcome the repulsive forces that act to keep them separate. Zeta potential is the potential at the slipping plane, the interface between the particle and associated double layer, and the surrounding solvent. Zeta potential measurements therefore quantify the magnitude of repulsive forces in system and the impact of strategies applied to modify it, such as changing pH.

If a suspension has a large negative or positive zeta potential then the particles within it will tend to successfully repel each other. Low zeta potential values, in contrast, increase the likelihood of flocculation. The dividing line between stable and unstable suspensions is generally taken as ±30 mV. Systems with zeta potentials outside of these limits tend to be thermodynamically stable. Zeta potential measurements therefore support the development of thermodynamically stable inks in the same way as rheological characterization supports the formulation of inks that are kinetically stable.

One final point to note when investing in instrumentation to measure zeta potential is that the combination of optical components that make up a highly specified DLS system also lend themselves to the measurement of both zeta potential and microrheology. Advanced DLS instruments such as the Zetasizer Nano ZSP from Malvern Instruments can therefore deliver a trio of measurement types that are relevant for ink formulation.

Further reading

To find out more about analytical strategies that are helpful in ink stability studies please refer to: ‘Keeping you in suspense’ by John Duffy and Steve Carrington an article published in August 2012 in Paints and Coatings Industry magazine. This can be viewed at the Malvern Instruments website.

For an introduction to microrheology see the Malvern website.

For help with understanding the capabilities of DLS systems:

An Introduction to Dynamic Light Scattering (DLS) | Malvern Panalytical

Zeta potential – An introduction in 30 minutes | Malvern Panalytical

By Jan Gorgol, Surface Measurement Systems Ltd, July 2014

Moisture affects a huge range of diverse materials in formulation research areas. For example, drug formulation performance can be critically affected by humidity changes leading to phase changes, hydration, crystallization and deliquescence of pharmaceutical powders.Other areas affected by humidity include solubility, hydrate/solvate formation, packaging, powder flow, tablet testing, aerosol and inhalers.

One of the many tools used to characterise the effects of moisture in formulation is microscopy , ranging from common microscopy using dark-field, bright field or cross-polarisation through to Raman, FTIR microscopy and more esoteric imaging techniques such as Atomic Force Microscopy , 3D X-Ray Tomography or even photo-acoustic microscopy (PAM).

In this article we present some case studies to highlight how different kinds of microscopy can be effectively used to study the effects of moisture humidity on real life formulation situations.

1. Crystallisation

Studies of crystallisation of amorphous samples under humidification include hydration of stable and unstable hydrates, deliquescence and liquefaction of hygroscopic samples, co-crystallisation and solvate desorption at high humidities. Polarized light microscopy and birefringence can be used effectively to study crystal morphological growth. Polymorphism can be studied by Raman, FTIR, and light microscopy (ref 1).  Light microscopy of amorphous lactose crystallisation with humidification can be combined with Raman data to show the change from amorphous to crystal state with increasing RH.

Raman Spectra of Amorphous Lactose Crystallisation:

2. Drug Development Studies

The behaviour and stability of potential drug candidates on exposure to water are critical in deciding which candidates are taken forward in drug development studies. Gravimetric techniques such as Dynamic Vapor Sorption (DVS) can be combined with FT-IR and a humidity cell to gain deeper understanding of the molecular changes occurring. This helps in the development of drug candidates with optimal stability / performance.

Naloxone HCL (an anti-narcotic substance) was used as a model system to study the effects of moisture sorption on active drugs.The water sorption and desorption isotherms showed jumps in the water uptake at 10% and 60% RH corresponding to formation of the mono and dihydrate. IR Intensity versus RH plots of these two peaks corresponding to the asymmetric water stretching frequencies at 3518 cm-1 and 3421 cm-1 showed a jump in intensity at 10% and 60% RH. These two jumps correspond to formation of the mono- and dihydrate forms and agree well with the gravimetric data.

3. Food

Effects of humidity on flowability of lactose due to changing amorphous and crystalline content were studied using Raman and light microscopy. Effects of humidity on dry milk powders were measured using light microscopy (ref 2).

R: Photographs of Milk powder at 64%, 81% and 85% RH:

4. Skin:

Using Raman microscopy combined with a humidity cell it is possible to image skin sections of skin/drug preparations to determine speed of adsorption of the drug, evaluate wound healing therapeutics and study skin ageing related to hydration.

5. Carriers:

Adhesion between drugs and their carriers with amorphisation due to humidity have been studied using atomic force microscopy.

R: Light microscopy of PVP drug carrier showing swelling and coalescence at humidity

Summary:

These are just a few areas where microscopy can be usefully used to study the effects of changing humidity on real life formulation samples. To help meet the many needs of scientists and technicians in these areas, Surface Measurement Systems have developed an environmental microscopy cell GenRH-Mcell (ref 3) to enable precise critical humidity microscopy studies in situ. Additionally, humidity critical studies can be undertaken via a variety of instrumentation by providing humidity generation as an add-on to other techniques such as XRD, 3D X-Ray Tomography, DMA, TGA, DSC, rheology, contact angle, aerosol EDB, optical tweezers, traps, particle sizing, and QCM. Conditioning regimes such as mechanical and texture testing, ball-milling, powder compaction, spray drying, freeze drying, and powder flow can also be emoployed.

If you have any humidity generation needs or questions in such areas please feel welcome to contact the author or join our Open LinkedIn discussion group on Humidity generation as an add-on.

About the author: Jan Gorgol (jgorgol@surfacemeasurementsystems.com) studied Physics at Bristol University followed by a Masters at Brunel University while working with XPS & SEM at the Experimental Techniques Centre. After working extensively in surface science instrumentation globally he now is Product Manager for the GenRH series of humidity generation products at Surface Measurement Systems.

References

 1. Dependence of cocrystal formation and thermodynamic stability on moisture sorption by amorphous polymer. David Good, Crystal Miranda and Naír Rodríguez-Hornedo: CrystEngComm, 2011,13, 1181-1189.

2. Surface Measurement Systems, Application Note 503 – Investigating Dried Milk Powders Using Optical Microscopy at Different Humidity Conditions.

 3. Surface Measurement Systems, Application Note 501 – Environmental Microscopy using the GenRH-A Humidity Generator and Mcell Accessory.

As scientists, all formulators have an inherent trust of data. As long as the data has been validated, then we expect objective decisions to be made and a project to proceed, or not, on the basis of hard data. However, a number of recent events have called into question, in my mind at least, the absolute validity of this when it comes to regulation and I am coming round to the view that emotions play just as large a role in some arenas.

So I’ve stepped onto my soap box and decided to explore the role of trust in subjects such as fracking, probiotics, GM crops, REACh and, most topically, the World Cup.

Fracking is a very hot topic in the UK with the government pushing hard for initial survey work which if promising, they would hope will lead to perhaps lower gas prices, but probably more importantly more energy security. Those vehemently against fracking claim that it will pollute water courses, initiate earthquakes and blight the countryside amongst other issues. One company local to where I live, has an exploratory permit to drill for oil and have issued a press release stating that they will not, and indeed are not permitted to “frack”. The environment agency and politicians have also said that there is no permission to “frack” but has this stopped a camp being set-up? Of course not! I am planning a press release saying that I am not going to build a nuclear power plant in my back garden, so am expecting some visitors in the near future!

In a recent article for “News and Views”,we explored issues that the producers of probiotic products have had with the European Food Standards Agency (EFSA) and the lack of accepted health claims for these products. Many reasons have been given for this, and the real problem is that, in the view of EFSA, the claims are not yet substantiated. They are not saying that the claims are incorrect, just that they are not proven, but I am now left to wonder if the consumer in Europe will believe future probiotic claims if they are ever granted. Does the consumer now believe that probiotics are “not safe”? A long battle lies ahead I believe. Will the probiotic industry in Europe be affected by delays in a similar way to the GM industry when the EU dithered over the GM potato, resulting in BASF stopping commercial activities in Europe in 2012?

One of the reasons for the introduction for the harmonised chemical regulation REACh in Europe was to prevent each country, or company in some cases, producing their own arbitrary blacklist of chemicals. The European Chemical Agency (ECHA) is intended to be the final arbiter and to be trusted to make correct decisions based on an agreed set of data. Has this happened?

What is my point in this “rant”? I’m not sure myself but I am convinced that scientists and formulators can no longer simply rely upon data and the regulators to come to a decision about their products. They must make their case to a wider audience and play on “softer” issues with the public, or some significant developments will not make it to the market.

Finally on the element of trust. We come to the World Cup. Trust in FIFA seems to be at an all-time low but does not seem close to resolution. I can assure you of one fact though for certain over the next month. England will miss a penalty – or two or three or four – and will unfortunately come home saying “Could have been!”

Maybe I will be wrong and you will never trust me again. If that is the case, what a night it will be on Sunday 13^th July!

David Calvert – June 2014

Many professionals involved in product formulation will come across spray drying technology or spray dried products at some stage in their career. Perhaps the physical form of a product needs to be optimised to increase particle size and reduce dust, or perhaps plant capacity utilisation needs to be improved. How can the practitioner start to tackle such problems, especially when he or she may have no formal training in the subject? Delegates at the new two-day training workshop “Spray Drying and Atomisation of Formulations”, run by the University of Leeds on 8^th-9^th April with support from iFormulate and ProCept, were able to answer these questions and many others.

Spray drying may seem a pretty simple process, but in fact there are a large number of factors which can be varied and these will all have an influence on the final product. With spray drying it often helps to start at the end of the process and decide what kind of end-product is needed. For instance, if a granular product is required, then it may be possible to agglomerate finer particles in the spray drying tower. The desired particle morphology and size, as well as productivity concerns, will in turn influence the drying parameters (residence time, temperature) and materials properties (solids content, rheology). Moving further back in the process, the fluid to be dried must have suitable rheology for fluidisation, pumping and atomisation.

With guidance from a diverse group of expert presenters and engaging laboratory demonstrations, attendees at the Workshop benefited from a packed programme that covered each of the main process steps in spray drying and provided case studies of applications from a number of different industries. In fact the wide range of industry applications represented amongst the speakers and attendees was very striking and included pharmaceuticals, food/beverages, detergents, catalysts and agrochemicals.

The training workshop was highly rated by both attendees and speakers and it is planned to hold it again in March 2015. Meanwhile the programme for the 2014 event is available on https://iformulate.biz/training-and-events/spray-drying-and-atomisation-of-formulations/.

Jim Bullock, May 2014

E: jim@iformulate.biz