Excipients

Background: 

Apart from active substances and/or functional ingredients, pharmaceuticals, food supplements and cosmetics also contain numerous excipients. These may constitute the physical matrix for the value-adding ingredients, enable technical processability, control the release of active ingredients, increase shelf life or improve flavour, for example. Ascertaining physicochemical and functional quality is therefore just as important for excipients as it is for active ingredients in order to ensure that promises of efficacy are met and patient/consumer safety is assured.

Strategic evaluation

Recent examples are once again emphasising the fact that greater attention must be given to the quality of excipients. Diethylene glycol and Ethylene glycol are known to be process-related impurities, which are not only found in such widely used excipients as propylene glycol, polyethylene glycol, sorbitol and glycerol, but also in macrogols. They are metabolised in the body to form the highly reactive metabolites glycolaldehyde, glyoxal and glyoxylic acid, which cause symptoms of poisoning and severe kidney damage. Following warnings in 2022 and 2023 ^[1], the WHO again drew attention to batches of propylene glycol contaminated with ethylene glycol in October 2024. (WHO 10/2024) ^[2]. Excipients obtained from natural sources, such as cellulose derivatives, can contribute directly or indirectly to the nitrosamine contamination of finished medicinal products to the same extent as synthetic excipients. Lipophilic excipients, such as waxes, oils or fats, can be contaminated with PAHs (polycyclic aromatic hydrocarbons), and toxic degradation products, such as peroxides, can be formed during storage. Many excipients may contain heavy metals, which can be attributed to the use of catalysts or heavy mechanical treatment during the manufacturing process. Limits for certain impurities may or may not have been defined for nominally identical excipients according to the respective markets (pharmaceuticals, foodstuffs, cosmetics). Some of the limits required for excipients in food supplements are derived indirectly from limits for the finished products.^[3] Manufacturers are therefore facing growing demands for assessments of the risk of impurities in their excipients and the implementation of specifications and tests as and when necessary.

Excipient analysis

Excipient quality is specifically tested in accordance with the relevant pharmacopoeia monographs and official conventional methods. Standardised methods from such collections as the ISO and EN standards. Although conventional methods may be less complex in technical terms, a high level of experience and stringent quality management in accordance with GMP and/or ISO 17025 are required in order to apply them for reliable, reproducible results. Whether identification testing as per pharmacopoeia monographs, testing for elemental impurities in accordance with ICH-Q3D, for diethylene glycol or ethylene glycol by means of gas chromatography, testing microbiological purity or for potential substance-specific impurities such as PAHs – trust in quality and security for your excipients!

We would also be happy to conduct a risk assessment for possible impurities, such as nitrite/nitrosamines, in your excipients and give you advice regarding the development of specifications.

Your contacts at PhytoLab:

Analysis:

DR. MONA ERNST
Phone +49 9163 88-784
mona.ernst@phytolab.de

Sales:

MARTIN MÜLLER
Phone +49 9163 88-5534
sales@phytolab.de

Sources:
[1] https://cdn.who.int/media/docs/default-source/substandard-and-falsified/n6_2022_contaminated-pediatric-syrups_en.pdf?sfvrsn=e8e0175c_6
[2] https://www.who.int/teams/regulation-prequalification/incidents-and-SF/full-list-of-who-medical-product-alerts
[3] https://kinderformularium.de/Hilfsstoffe