Use of cyclodextrins as excipients in pharmaceutical products: why not in extemporaneous preparations?

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

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

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-esta blished 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.

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.