Cyclodextrins are ring-like assemblies of sugar units that are used to solubilize active pharmaceutical ingredients (API) to boost bioavailability and improve stability.
They are also used as barriers to seperate actives in combination products to prevent drug-drug interactions as well as to mask the taste of bitter actives and to convert liquid drugs into powders.
At present cyclodextrins do not have to be listed on drug information leaflets.
However, the EMA said it is considering introducing the requirement that their presence be stated as a precaution “because of limited information and possible interaction with active substances.”
Animal studies
Specific regulatory concerns range from the slight risk that high oral doses of cyclodextrins have been found, in animals, to cause temporary diarrhoea and to the damage the epithelial cells of the rectum.
Cyclodextrins in ocular drug formulations are also the subject of the review following the discovery that, at certain concentrations, the alpha-CD and RM-beta-CD forms of these chemicals are toxic to the corneal cells of test animals.
The EMA said that: “Although the oral availability of cyclodextrins is very low, high doses may cause reversible diarrhoea and cecal enlargement in animals, and therefore also in humans to some minimum extent.
“Depending on their amount, cyclodextrins may influence the permeability of tissues and therefore the bioavailability of active substances given topically. Cyclodextrins can cause nephrotoxic effects in animals at high systemic exposure.”
The deadline for industry comments is February 28. No deadline for adoption has been set.
The cyclodextrin consultation is part of a rolling review of excipient labelling requirements undertaken by the EMA since 2011 following revisions to guideline on CPMP/463/00 introduced by the European Commission (EC).
The EMA also released a similar Q&A document on a second excipient propylene glycol, which is used as humectant, solvent and preservative in a wide range of medicinal products.