Call for feedback by EMA on plans to require drug makers to state whether their drugs contain solubility-enhancing cyclodextrin excipients

Cyclodextrins are ring like assemblies of sugar units that are used to solubilise active pharmaceutical ingredients (API) to boost bioavailability and improve stability. They also act as barriers to separate actives in combination products to prevent drug-drug interactions as well as to mask the taste of bitter actives and to convert liquid drug into powders.

The European Medicines Agency (EMA) said that it is considering to introduce the requirement that the presence of Cyclodextrins be stated as a precaution “because of limited information and possible interaction with active substances". Therefore it is under the rolling review of excipient labelling requirements undertaken by EMA since 2011 following revisions to the guideline on CPMP/463/00 introduced by the European Commission. The EMA is thus inviting feedback from the industry by February 28, 2015.

Special regulatory concerns point out that high oral doses of cyclodextrins have been found in animals causing temporary diarrhoea and damage of epithelial cells of rectum. It has also been found that at certain concentrations the alpha CD and RM-Beta-CD forms of cyclodextrins are toxic to the corneal cells of test animals. Therefore based on the above facts the EMA said that "although oral bioavailability of cyclodextrins is very low but high doses may cause reversible diarrhoea and cecal cell enlargement in animals and to some extent to humans also and depending on their amount the cyclodextrins may the bioavailability of active substances given topically.