Formulation Science: Continued


In a recent blog post, I discussed the essentials of the Formulation Science discipline, using a long explanation involving cake. I am not a Formulation Chemist, but I quite liked writing this post. For my own enjoyment, and to be more technical, here’s a follow up!

The Role of Formulation Science

So, Formulation is an essential discipline, but specifically why? As a synthetic chemist, I deal with chemicals in their purest forms. And the majority of organic chemicals manifest themselves as unassuming white powders. These are not acceptable as consumer products for several reasons. Namely:

  • Regulation
  • Marketing
  • Storage
  • Consumption
  • Delivery

I’d like to explore all these functions in more detail below.


Before a product can go to market, it is regulated by its relevant industry agency – be it the FDA, MHRA or EC. These agencies exist such that consumers know what they are buying is what it says it is, and that it is safe. It’s as simple as that.

Pure chemicals are not good consumer products because they are unlikely to be efficacious. Therefore formulations are necessary to dilute them down to consumable levels. These formulations must be uniform so that the consumer knows exactly what they are getting.


If you know of or remember the Herbal Essences marketing campaigns, you will be aware that scent is an attractive attribute for a shampoo formulation to have. You can mount your entire marketing strategy based on it, it seems.

Marketing can also use appearance or texture to sell their food products. Though whether either is actually central to the marketing in my examples is disputable, what is indisputable is that these are desirable qualities.


Substances, whether they be shampoo, food or medicine, must be storable until they are consumed. The product can smell delicious and have the perfect gooey texture of the perfect shampoo, but if it smells of mould and separates into a liquid and solid after a week it is not acceptable.


You also want the formulation to afford the stability to maintain those desirable qualities that have been instilled in the property. Loss of flavour or texture is not something we want in foodstuffs. Ice cream, for example, contains anti-freeze molecules to ensure it does not turn into a solid block of ice: instead it maintains a soft, scoop-able texture.

Desiccants are substances that absorb moisture. These are often included in packets to avoid the product absorbing the moisture in transit to the consumer, but they are also included in formulations to ensure, for example, that a laundry powder doesn’t clump up. In solid formulations, products are often spheronised (to form sphere) and coated to aid longer storage and slower release.

Finally, medicines. Indisputably, we want these to maintain their medicinal properties even after we have opened the container. Essential reactive ingredients need to be formulated such that they don’t break down when exposed to heat or moisture. Otherwise, medicines would be far more expensive and equally far less useful.


This ties into the marketing section somewhat, as many of the formulated products we buy are for consumption. It is important to instil pleasant scents, textures and flavours into foods and soaps, but also into medicines to enhance patient compliance.

However, it is important that products must be safe to consume as well. Reactive ingredients are included in products simply because they react with the body in some way. But it is undesirable to expose the body to too high a concentration, as they can be irritant or even toxic. Formulations both dilute these chemicals and structure the mixture so that they are released more slowly.


This section I have included predominantly to discuss medicine formulations. And this is the area in which drug companies expend most of their research, so I am unlikely to do more than touch upon it here.


Drugs cannot contain chemicals that are toxic to the body. Unless they need to, for therapeutic purposes.

This is the paradox that drug companies encounter with their products. Any effective drug will alter the activity of a cell, protein or receptor within the body. And therefore we want the drug to do this only where it will help us.

Drug molecules must therefore be formulated to be released only where we need them, and to release at the correct rate so as to be effective. Many tablets are broken down by the acid in the stomach, thereby releasing their drug loads. These drugs are therefore formulated such that they will have a high enough dose to hopefully reach the area of interest even when delivered to everywhere else in the body simultaneously. But equally, they must be formulated such that they will not cause damage when they are non-specifically delivered to areas outside that of interest.

For this, drugs must not have toxic break-down products that will damage the body when they encounter the rest of the gastro-intestinal system or are broken down in the liver. Chemists that know their drug will be broken down in a particular organ can alter them chemically such that only their breakdown product will be reactive (enhancing the slower release profile).

Much of the specificity drug delivery process is covered by the actual structure of the drug lead compound – this is why we have hybrid protein or polymer conjugates on the market. But the role of the Formulation Scientist must not be underestimated.




(1) An excellent online resource on cosmetic chemistry, which is a form of formulation science.

(2) The RSC subgroups pages on formulation.

“What are all these chemicals for?” – aka, a very basic primer on Formulation Chemistry

Formulation Science?

I’m currently studying for a PhD in Chemistry, and yet never during my Chemistry Undergraduate or Postgraduate career have I come across any modules or even seminars touching on formulation science. This is largely because formulation science is seen as an industry staple, something that doesn’t have a place in more blue-sky, academic research such as university is geared towards. Formulation, outside of industry, is considered more something that a good chemist will be able to pick up on the job.

And yet, it is an absolutely crucial discipline. Formulation scientists do exactly what you might expect from the name: formulate the complex mix of chemicals that makes up a tablet, powder, aerosol, gel, cream (etc.). Without them we wouldn’t have shampoos, deodrants, paints, medicines and even some foods.

But why all the chemicals?

Funny how you might ask that, reader, but everything is made up of chemicals. Foods found in nature actually have a colossal number of different chemicals in them. This is because a very delicate balance is required to maintain a stable, pallatable formulation.


Having a mix of chemicals means you can more finely tune the properties of a particular substance. Think of it like a carrot cake.

Formulating a Carrot Cake

In all cakes, you need butter, margarine or oil to lubricate the mixture and enhance the texture of the finished product. For a carrot cake, you also need self-raising flour and baking powder. Proteins within the flour form a network of gluten when mixed with moisture, which allows the cake to rise. Baking powder creates bubbles of air in the mixture which enhances this rise.

To enhance the flavour of our carrot cake, we also add in some cinnamon, nutmeg and ginger. Sugar also enhances the sweet flavour of the cake – but in addition it absorbs moisture from the mix and thus avoids the cake from getting too hard.

Carrots and orange zest are also needed to tune the flavour of the cake (the former giving the cake its name, after all). However, these ingredients also add moisture to the mix that it would not have otherwise. The quantities of the other ingredients must thus be altered to allow for the inclusion of the wet fruit and vegetables to stop the final product being too dense.

Last but certainly not least: eggs. Eggs are an emulsifier, meaning they can help in the combining of oily and watery mixtures. In cake, they help to combine the liquid and solid ingredients into an even mix. And this is even without thinking about the icing!


So you see, it is essential to consider the exact properties you need for your final product, and to tailor the ingredients to ensure you achieve this. I’ve found that chemists are well-suited to baking for precisely this reason: they appreciate the complexity and intricacy of a good formulation.



(1) An excellent online resource on cosmetic chemistry, which is a form of formulation science.

(2) The RSC subgroups pages on formulation.

(3) Article showing three naturally occurring foods’ chemical “ingredients list”.

Let’s have a talk about homeopathy

A note from the author: As this is an emotive subject, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.


As my first post in a very, very long while, I thought I’d post an extended discussion about some aspects of homeopathy.

Homeopathy is an alternative medicine (as stated in Tim Minchin’s famous song), based on the theory that “like cures like”.(1) This means that “a substance taken in small amounts will cure the same symptoms it causes if it were taken in large amounts”.(2-5)

As I work as a research Chemist, I have to state that I am biased when it comes to alternative medicine. To me, science must be evidence-based to have value; and thus medical practice, which is based on the science, should also be inherently evidence-based. By “evidence-based, I mean there is insufficient scientific research to justify the inclusion of homeopathic method in the standard library of standard medical treatments.(4)

However, in order to fully examine the potential of this theory, I believe it is worth discussing some instances where the homeopathic approach might actually be successful. In doing so, perhaps we can find a reason for the use of alternative medicine by so many people.


Successes: X-rays


In the modern age, cancer treatment is either through the use of chemicals (chemotherapy) or radiation (radiotherapy). X-rays were discovered in 1895, soon after which scientists unlocked their use in therapeutic applications. In 1986, Emil Grubbé (a physician with training in homeopathy) assembled an x-ray machine and used it to treat a recurrent breast carcinoma.(6)

Though unsuccessful at first, Grubbé’s treatments were potentially more successful than others due to his use of lower exposures for less time, and throughout the rest of his life he taught many others his techniques. X-ray radiation therapy today actually uses a “fractionated” process where low doses are administered over a longer course of time to minimise side-effects.(7)

Homeopathic theory in the case of X-rays works because they kill cells. Therefore it stands to reason that a low dose is best to avoid killing the desired cells. Our intrepid homeopathic physician, Grubbé, unfortunately, fell foul of the damage that X-rays can do at higher exposures, and himself had to undergo many surgeries to treat recurrent cancers.


Successes: Hay Fever


As another example of homeopathic “success”, let’s look at hay fever.(8-11) The majority of people with hay fever can simply avoid the pollen that triggers it in various ways, or take anti-histamines. Those with more sever allergies may be referred to immunotherapy. Immunotherapy is a treatment where the body’s immune system is exposed gradually to increasing levels of the allergen (pollen), such that their immune cells become tolerant.

The reason to only gradually increase the dose is to minimise side-effects, but this does mean that it takes a long time to reach the point at which the patient is “cured”. At this point, they must take maintenance doses to sustain tolerance. It stands to reason, then, that exposure to allergens (at a homeopathic dose) would potentially reduce the symptoms for some hay fever-sufferers as a form of immunotherapy for those with less severe symptoms.


Why successful?


So what do these two “successes” have in common? Both are situations where the homeopathic approach happens to coincide with what we currently use in medical practice anyway. They work because exposure to X-rays kills cells, and we want that to happen in cancer treatment. Lower doses result in less peripheral cell deaths and thus less side-effects. They work because pollen induces immune cell responses. Lower doses result in less immune cell responses and thus less side-effects (and thus immune cell tolerance). These are both therapies where evidence exists for their success.


As Tim Minchin says, “Do you know what they call alternative medicine that’s been proved to work? Medicine.”(1) But that’s not the appeal of homeopathy.

Stripping down the theory, people like homeopathy because it is “natural”, using the same “natural” cause of a disorder to fix it. And they like it because it has few side-effects. Let’s explore these things.


The Unfortunate truth


Alas, this is where I look less optimistically into homeopathic method. This is because, as a Research Chemist, I am used to spending my days purifying chemicals and diluting them down to acceptable concentrations for use on cells or proteins. Side-effects tend to occur where the given dose of a drug has effects beyond the desirable local effects. The reason that homeopathic remedies have little to no side effects is because the doses are so low as to have no effects in the body.


The homeopathic dilution method uses a logarithmic scale, with C being a dilution by 100 and X being a dilution by 10.(12) A 2C dilution is 1 part in 100, repeated twice (so 1 in 1002 final concentration), 6C is 1 part in 100 repeated 6 times (1 in 1006 final concentration). A 10C dilution is 1 part in 10 repeated 10 times (so 1 in 1010 final concentration) etc etc…

As I have never taken a homeopathic remedy, I had a cursory glance at some online shops to see if anything interesting popped up. I found Mercurious Chloride (Calomel, Hg2Cl2 – I will refer to it as Mercurous Chloride, it’s proper chemical name).(14) This is acutely toxic, causes respiratory sensitization and is hazardous to the aquatic environment according to Sigma-Aldrich, but that is not mentioned on homeopathy suppliers’ websites.(13-14) Not to spoil the surprise, but this is likely because of the very small quantities of active ingredients.

Let’s do some Maths. One supplier offers a pack of 160 g of tablets at 6X potency (for £22.35). 6X potency is 1 in 106 – so 0.00016 g of Calomel is in this 160g. From the shop I looked at, each tablet was approximately 0.11 g.

So, per tablet, we are looking at 0.00000011 g of the chemical. This is a tiny, tiny amount.

The amount of mercury in the water supply (determined to be a entirely safe amount that has no effect) is around 1 microgram per litre.(15) So 1 l contains 0.000001 g of the chemical: or, around ten times as much as in a homeopathic tablet. Frankly, this makes it obvious why people claim that homeopathic remedies are placebos (medicines with no therapeutic benefit).

The cost for this 0.00016 g of Mercurous Chloride is also extortionate: considering that 5 g of the pure chemical would cost less than £30, the mark up is therefore more than 2,300,000%. The numbers speak for themselves.

Natural Remedies

I’d also like to briefly step on the issue of “natural sources”. Some Mercury is purified from mined cinnabar (HgS), and this source gives the most “natural” method (the least steps) of Mercurous Chloride production:

Step 1) Cinnabar ore is heated in air and the resulting Mercury vapour is condensed and collected.

Step 2) Mercuric Chloride is formed by adding Hydrochloric acid to this elemental Mercury.

Step 3) This Mercuric Chloride is then reacted with elemental Mercury to form our Mercurous Chloride.

In the modern age, there is an increasing trend to consume “natural” food and to “detox” your body. It therefore stands to reason that people are concerned about putting potentially harmful substances in their body. I completely understand this and I subscribe to keeping a healthy diet. However, it does not apply when it comes to medicine.

Pure chemicals do not occur in nature, and thus natural remedies are not inherently more safe than those prepared in a lab. Chemical intervention is needed in every case to obtain pure substances, whether for purification or (in this case) to actually make the chemical in which we are interested. Regulated homeopathic remedies are always subject to some form of purification before they are sold on. I would be far more concerned about anything unregulated, as you cannot know whether you are consuming something harmful. If the mood calls for it, I’ll be happy to discuss the natural vs. natural debate at another time, but I have no time for it here.


But what’s the harm?


What is the harm indeed? If people are willing to spend lots of money on something that has no effect, then it is their choice.

This has been discussed before, and I don’t want to retread very well-trodden ground, so I’ll just summarise here. Individuals using homeopathic treatments instead of conventional medicine are spending more money for treatments that, more often than not, do not work.

A good book to read on this issue is “Trick of Treatment?: Alternative Medicine on Trial” by Simon Singh and Edzard Ernst. There are also other articles on the same subject such as here.


What can we learn from homeopathy?


So here’s where I go back to my original thoughts. What is the potential in homeopathy?

The inherent value of alternative therapy is that people are different. Not all people like to be told that there is one, and only one, way of curing your disease or disorder. Being treated by alternative medicine is like being part of an exclusive club, like being a medical hipster – and there are huge online communities dedicated to discussing it. These communities have their own “experts” – people who have tried homeopathic treatments and recommend them to others. Obviously people like to feel like they understand what’s going on in their own life, and health is potentially the most important aspect. And subscribing to alternative therapy is one way of regaining control.

Is it really worth it though? Homeopathy becomes most attractive where patients are at their most vulnerable. Where patients are scared to take a nasty treatment with known side-effects, or when they have no other available treatment. Homeopathy cuts through the jargon of complex medical treatment and uses simplistic theories that anyone can “understand”. But, in doing so, the industry takes advantage of a patient’s vulnerability.

It’s easy to blame your condition on toxic chemicals and unnatural sources. It’s hard to admit that sometimes your body needs outside “unnatural” help in the battle against a disease, especially if it’s a battle you’re losing. But if you broke your leg, you would get it fixed. Internal “breakages” also need medical intervention.




What is my conclusion? Listen to your doctor. They are trained in treating human diseases and disorders; in fact, they have dedicated their lives to it. Talk to them about your concerns. If they dismiss them, then speak with them more: it’s their job to listen to you. Nowadays medicine is more patient-focussed and doctors should be willing to work with their patients. Doctors will be able to determine where a homeopathic treatment may be appropriate for you, as in the above cases.

If your condition is beyond help with conventional methods, by all means homeopathy may help you. If your conviction is strong enough that a placebo is sufficient, try homeopathy. But really nowadays homeopathic treatment is best alongside conventional medicine: there’s a reason it’s sometimes called complementary medicine.

If you want to try homeopathic treatment, just make sure it’s from a reputable source, and that it’s safe.




This blog is my opinion only, and it is largely my personal exploration of homeopathy as a treatment. In the case of X-rays, I have compacted an extremely large amount of information into a short space, so please do have a further look at the literature if you are interested! In particular, I would recommend the book “Strange Glow: The Story of Radiation” by Timothy Jorgensen.

Also, I am aware that I did only one calculation for the homeopathic remedies. So here is another, for fun:


Homepathic remedy:

Alium cepa (red onion)

160 g, 3X potency, £22.35

3X potency is 1 in 103

This is 0.16 g onion in the 160 g

Each tablet is 0.11 g; so, per tablet, we are looking at 0.00011 g of onion


Tesco medium red onion:

1 onion (according to is £0.16, about 220 g

The amount in one tablet is therefore one two millionth of an onion.

The mark up for this remedy is therefore 19,000,000%.

And another, as requested:

Homepathic remedy: Weleda Sulphur 30c 125 Tablets

125 tablets, at £0.05 per 100 mg tablet
30C potency is 1 in 100 to the power of 30
This is 1 x 10^-61 g of sulphur in each tablet

– Please note that the mass of a proton (the smallest chemical element) is 1 x 10^-23 g. This is less than that. This means that, in one tablet of this stuff, there is not even one atom of sulphur present.

Sulphur from Sigma-Aldrich (chemical company):

This is £26.50 for 1 kg.
The mark up for this remedy is 2.65 x 10^64 %. Which is 265 with 62 zeroes after it %.


  1. Tim Minchin’s song, Storm:
  2. British Homeopathic Association Website, accessed 19/06/16:
  3. The Society of Homeopaths’ Website, accessed 19/06/16:
  4. Science and Technology Committee evidence check on homeopathy, 8th February 2010:
  5. Homeopathy on NHS choices, accessed 19/06/16:
  6. Nice article on the use of X-rays in radiation treatment:
  7. The evolution of cancer treatments: Radiation, accessed 19/06/16:
  8. Hay fever on NHS choices, accessed 19/06/16:
  9. Hay Fever on Allergy UK, accessed 19/06/16:
  10. Kim LS, Riedlinger JE, Baldwin CM, Hilli L, Khalsa SV, Messer SA, Waters RF (2005). Treatment of seasonal allergic rhinitis using homeopathic preparation of common allergens in the southwest region of the US: a randomized, controlled clinical trial. Annals of Pharmacotherapy; 39:617–624.
  11. Reilly DT, Taylor MA, McSharry C, Aitchison T (1986). Is homeopathy a placebo response? Controlled trial of homeopathic potency, with pollen in hayfever as model. Lancet; ii: 881–885.
  12. Homeopathic preparations, Wikipedia, accessed 19/06/16:
  13. Mercury(I) chloride on Sigma-Aldrich:
  14. Helios homeopathy shop, accessed 19/06/16:
  15. Water purification standards, accessed 19/06/16: or

Problems in Pharmacology: Clinical Trials and Molecular Markers

This week’s post follows on from something I touched on last week: the issues in the drug design process.

Drug design tends to be stem either from mimicry of molecules the chemist knows that the drug target already interacts with (such as a substrate that binds to an enzyme) or from knowledge of the potential’s drug target’s structure (where computer modelling, for example, can suggest which would be the best structure for a potential drug).Resized

These drugs are synthesized, and then undergo preclinical testing. This involves assessment of their stability and their interaction with an isolated drug target (called in vitro testing), and then testing inside animal models. After these stages, totalling up to 6 years, the drug will go to clinical trials in patients.

Clinical trials are in three stages, with the amount of patients in each stage increasing as confidence in the drug’s capabilities develops. The final stages are then approval by the authorities and marketing. This drug discovery process takes in total anything between 10 and 16 years and will cost the company up to a billion dollars. And yet, there are still issues with drug safety that slip through the net: think of thalidomide as the most popular example! Why is this?

There are a multitude of reasons of course. Once a drug has reached later trials, a company can become invested in it and wish to push it through. There may also be signs that the drug is unsafe missed, which may come from the design of the clinical trial itself.

In clinical pharmacology, a biomarker is a characteristic the patient has that can be measured during clinical trials, and is used as an indicator of their biological state. For example, a biomarker such as glucose or hormone levels can indicate the likelihood that a patient will get better or relapse.

A key issue with clinical trials is that they do not measure all relevant biomarkers. A different drug for the same medical condition will have a different action (mechanism) in the body and therefore will have a different effect on biomarkers. They may effect biomarkers that were unaffected by other drugs.

Therefore, in order to fully understand the effect of the drug in the body and truly assess its safety, trials should be randomised with controls (patients taking “placebo” pills with no drug in them to show how biomarkers might change with no drug present). The system currently unfortunately relies on the validation of biomarkers to display patient health, which is both a lengthy and difficult process.

New clinical trial designs are therefore being considered, such as the “I-SPY 2” trial which uses molecular tests to tailor treatment or “BATTLE” which uses biomarkers to tailor the treatment. These new designs are quite new, so unfortunately I am unable to provide more detail than this!

The future of drug discovery seems to be tending towards the more in silico side of research, which uses computational modelling of drug action to suggest how a drug will act in a given system. The future looks bright here, but again that is a discussion for a later post!

I based this post on a talk at the EACPT 2013 conference by Professor Max Parmar (UCL). This post is entirely my own opinion, based on my own experiences – feel free to disagree and share your thoughts in the comments! I’ll be continuing on the “Problems in Pharmacology” theme next week!


A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Problems in Pharmacology: Definitions and crossing the Biology/Chemistry Border

I thought a good way to begin this blog was with a series of posts dedicated to defining what exactly pharmacology is, and the inherent difficulties in studying  and practicing it. First of all: definitions!

Chemistry is the study of the composition, properties and behaviour of matter, whilst biology is the study of life and living organisms.Resized

Pharmacology is a boundary science, by which I mean it lies firmly on the border of chemistry and biology, dabbling in both but not really studied by scientists within either of these disciplines. Broadly speaking, pharmacology is the science associated with the study of drug action within a living organism.

And therein lies the problem: in order to truly be a pharmacologist, one must not only understand the structure of a drug, one must also be able to ascertain all interactions with the patient’s cells and biological molecules. This is really, really hard.

As a chemistry student, I have also taken modules in biology. The issue with studying biology as a chemist is that modules designed for chemists differ greatly from those the biologists study – imagine the chemistry student looking through a soundproof viewing window into a biology lecture, unable to hear the words, but being able to see some of the diagrams, and given a description of them by a chemist standing next to them.

It is much the same in biology – having taken modules in the life sciences, chemical subjects are approached as though the subject matter should inherently be treated as alien. Unfortunately, at undergraduate level at least, this is unavoidable.

Students on three or four year courses cannot entirely straddle two departments, where lecture modules later on usually depend on some understanding of several modules taken in earlier years. There is just not enough time to learn every module needed, unless a student decides to specialise in a boundary science at the very onset of their degree. This appears to be a massive commitment, which I personally did not wish to make at the age of 18.

These degrees, such as biochemistry, do not tend to entirely cross the boundary either, they tend to be taught predominantly in one department or the other. Chemistry and biology teaching methods require different learning styles. Having done a variety of these modules myself, I find it awkward to switch between the chemistry style of understanding of process and the biology style of memorising definitions and mechanisms.

As the depth of our understanding in these disciplines increases, such boundaries may only widen. But this is not necessarily a bad thing – it is simply a product of progress, which in science is always good!

Though at undergraduate level it may seem that biology and chemistry are miles apart, upon reaching research level this is not so. More and more research groups contain both biologist and chemist specialists, who may benefit from each other’s knowledge. Many universities recognise chemical biology modules as an essential part of a chemist’s degree, more in silico (computation) research focuses on interaction of proteins and enzymes, and more of the more specific areas of chemistry are opening up to biomedical application.

This is a promising start to widening study of pharmacology and other boundary sciences, but it is not the end. Pharmacology in particular seems to be a specialist science studied mainly in hospitals by clinicians.

Picture1Because the science relies on clinical trials (or in silico research, which I’ll discuss later), it is often overlooked by academic researchers and undergraduates. Although pharmacological research would, ideally, be implemented into the earlier stages of drug design, it is often carried out reactively rather than pre-emptively. I think I’ll leave this discussion for now, though: pharmacology in drug design could fill an entire post by itself!

I feel that a solution to undergraduates being underexposed to the more specific areas of chemistry and biology would be to have lecture series for active researchers just to discuss their specific disciplines. Of course, this sounds very basic, and it is! Different universities tend to churn out scientists specialising in the area the university department itself tends to specialise in. Exposing their students to other areas of research could lead to more well-rounded researchers with a greater understanding of the scientific world as a whole.

This post is entirely my own opinion, based on my own experiences – feel free to disagree and share your thoughts in the comments!


A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.