It could be seen as a minor aspect of the drug development process, given the time and expense that goes into the discovery of a drug that is effective for a particular condition, but the choice of colour for a capsule or pill holds greater significance than first meets the eye.
Research has shown that switching patients from a branded medicine to a generic pill of a different colour leads to a 34% increase in the risk that they will be non-adherent to their medication regimen.
Choice of colour can also have a significant impact on sales, with some generic manufacturers choosing to follow similar pigment colours to originator products for brand recognition. In this example, AstraZeneca (AZ)’s brand for its Nexium (esomeprazole) product was of such importance to the company that it pursued legal action, resulting in Dr. Reddy’s changing the colour of its generic medication.
In-PharmaTechnologist (IPT) spoke to Nicolas Madit (NM) to discover why such a seemingly small change, in the colour of capsules or tablets, can make all the difference when taking a treatment to the clinic, regulators and patients.
IPT: How is colour utilised in the capsule industry?
NM: First, it is important to understand why colour is important. You have a lot of needs to fulfill. One of the first needs is branding. I'm sure in the US, if you ask people about the purple pill [AZ’s Nexium], they all know its name and that it’s good for stomach acidity.
[For Nexium], the colour is more or less pronounced depending on the dose – you can play on this by giving the lower strength dose a lighter colour and vice versa.
Another important point is security. For example, there was a case that happened in France – a diuretic had to be withdrawn because of suspicion that some packs contained a sedative. In fact, that was not the case at all. What happened was that a geriatric patient had, by mistake, taken the wrong pill because they had two different tablets that were both white and practically the same size. If one of them had been coloured differently than the other, then the problem may have been avoided.
In addition, some colours may be easier for a child to accept rather than a white capsule. So, you see, colour is crucial.
IPT: How does a company usually choose a colour?
NM: When pharma companies want to launch a product, they will have to look carefully at the colours they would like to use. When R&D is requested to develop a new product, their first question will be, “Tell me, what is the colour of the capsule?” The majority of the time they will have not yet decided on a colour. So, in general, they will take a white capsule and test it for stability. Five or six months later, the marketing team will come back and say, “We have chosen this packaging, so we would like this capsule colour.”
What happens then is that R&D has to do everything again, from the beginning, with the correct colour of the capsule. Although they made the first pre-evaluation of stability, this six-month investment is now lost.
IPT: How can this type of time loss be minimised?
NM: By listening to customers facing these problems, we identified its impact on their development time. This challenging situation was an opportunity to come up with new ideas to help them. Our customers have told us about their difficulties with colour development, so we have said: why not give them a capsule that has different pigments and colours, and is chosen in a way that is globally accepted? With this, they can do their stability testing.
Then they can come back to us after six months, even after one year, and based on what they have studied, they can say, “My active ingredient is stable with all these colours at these levels. So, I'm going to choose my colour by combining two or three of these pigments, at this level or less, so that I can have the colour I need without having to do another stability test.”
When they want to choose a colour, in our gelatine Colorista capsules, they can choose from 150 different colours; in our hydroxypropyl methylcellulose Colorista capsules, they have 50 options. In fact, these colour options end up with thousands of different body/cap combinations. With this service, they can save time and resources and go rapidly to the market with only one capsule.
IPT: What other areas does this help with?
NM: In the US, if you test with Colorista then you can come with the finished product to regulators saying, “My final batch was made with Colorista and it has proven that it is stable. The final colour is based on dyes or pigments at the same or at a lower level than used in Colorista.” For the regulators your study is considered valid.
Nicolas Madit is business development manager at Lonza Pharma & Biotech. After graduating with a degree in chemical engineering from Montpellier, Nicolas completed his PhD in organic and polymer sciences, followed by a postdoctoral scholarship on synthesis of co-polymers as specific transportation vector for drugs.