Objective:

To conduct an assessment of cyclodextrins used as excipients in pharmaceutical formulations, considering compounding, biopharmaceutical-pharmacokinetic, toxicological, regulatory, economic and commercial aspects.

Method:

A literature search was performed of highly cited review and original articles. Regulatory and legislative documents and well-established pharmacopoeias were also consulted.

Results:

Solubility, resistance to hydrolysis and complexation efficiency are variables that depend on the cyclodextrin itself and on the drug to be complexed. In some cases, addition of excipients is necessary to improve complexation efficiency. Complexation of drugs with cyclodextrins at laboratory scale tends to be rather inconsistent. Moreover, wide variations exist for the same cyclodextrin across different suppliers and even across batches from the same supplier. This means more control analyses must be carried out of pharmaceutical preparations. Problems with the stability of cyclodextrin-drug complexes could affect the oral bioavailability of the drugs. Additionally, some cyclodextrins may optimize the drug's permeability through specific biological membranes and the length of time it remains in contact with them. Despite the safety profile of cyclodextrins, exceeding certain dosing thresholds and administration times might cause adverse effects. Only cyclodextrins recognized as excipients by well-established pharmacopeias should be used in pharmaceutical compounding. Cyclodextrins lead to an increase in the global costs of compounding and their purchase through recognized suppliers is often unfeasible.

Conclusions:

Despite their interesting properties as excipients due to inclusion complex formation, the need to carry out more quality control analyses and stability constant studies, combined with the high cost and difficulty to purchase cyclodextrins, may explain why their use in pharmaceutical compounding is currently not a viable alternative.