Chemicals & raw materials
But there are some parameters: all excipients share a number of key properties. As Bashir outlines, excipients must be inert (they do not react with the active pharmaceutical); non-toxic (they do not cause damage to cells and tissues); cheap; and stable in high relative humidity and moisture conditions for storage purposes. Excipients have no medicinal properties, then, but their application in drug formulation is wide ranging.
“Although research has demonstrated positive responses and future promise, the biggest issue is the scaling up of these specialised advance formulations and the cost of manufacturing.”
For tablets, Bashir explains, excipients are “primarily used as bulking agents, since the active drug is in very small quantities. They are also used to prevent the drug from adhering to tableting machines during production, as flavouring agents, as sweetening agents, and as disintegrating agents”. It’s this last function – the excipient as disintegrating agent – that explains the transformation from hard tablet into active drug in the stomach. “Disintegrating agents are really important,” Bashir explains. “They mix in with the formulation, the formulation is compacted into a tablet, you take the tablet, and in the stomach the disintegrating agent will absorb water and swell, so that the tablet breaks up very quickly and releases the active ingredient.”
Inertness in common It’s not only tablet formulations that include excipients – liquid preparations, both oral and injectable, require
them too. In oral solutions, Bashir explains, excipients can be used as “preservatives to increase shelf-life, as thickening agents, for flavouring, or for pH adjustment, to reduce chemical degradation and unwanted hydrolysis”, while injectable drugs need excipients for sterilisation, preservation and as a tonicity adjuster, to prevent pain at the point of injection. Arguably, the single unifying property of all excipients is inertness; but that doesn’t mean that excipients can’t cause reactions. “Side-effects can occur from certain excipients”, Bashir says. “Cheaper generic products can contain excipients such as lactose that can cause diarrhoea. Excipients that contain sugar and sweeteners have to be taken with caution by diabetics. Certain formulations have very high salt content (such as Gaviscon), so must be taken with caution by patients with heart failure or hypertension.” It is imperative, therefore, that formulation scientists, producers, and regulators of excipients are mindful of potential reactions and side effects like these. As Bashir notes, “pharmaceutical manufacturers must put patients above profit and ensure that the excipients used are not known to cause reactions or side-effects” and it is vital that scientists “check various guidelines” issued by regulatory bodies like MHRA, European Medicines Agency or FDA, before selecting an excipient for use.
One of the most important regulatory bodies for excipients is the International Pharmaceutical Excipients Council (IPEC). Established in 1991, and now with divisions in the Americas, Europe, Japan, China and India, IPEC is the global industry association that develops, implements, and promotes the use of appropriate quality, safety, and functionality standards for pharmaceutical excipients and excipient delivery systems. Working with member companies that span the whole excipient chain – from producers to developers, manufacturers, and users – IPEC’s mission is to develop and promote harmonised and internationally accepted guidelines to improve patient safety.
Disintegrating agents enable the transformation from hard tablet into active drug in the stomach.
Brave new world
The growth of IPEC in the past 30 years indicates the extent to which attitudes are changing towards excipients in the pharmaceutical industry. Today, the excipient market is huge, with suppliers around the world including Evonik, BASF, Dupont and Merck, to name a few. According to the 2021 ‘Excipients in Pharmaceuticals: Global Markets to 2026’ report, the global market for pharmaceutical excipients is predicted to grow from $8.3bn in 2021 to $10.6bn by 2026.
Part of the reason for this growth may be because excipients could hold the key to the future of innovation in drug formulations. As Bashir explains, “solid dosage forms that are taken orally are the ideal formulation both from a
34 World Pharmaceutical Frontiers /
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