Cyclodextrins (CDs) have long been known and used as functional excipients in different pharmaceutical dosage forms. The last 40 years in CD technology has witnessed the successful utility of CDs for stabilisation, solubilisation and bioavailability improvement of poorly soluble APIs. At present more than 40, CD-enabled human pharmaceutical products are on the market.<br/>Recently, the therapeutic uses of “empty” non-occupied CD nano cavities have been emphasized. The first such application was published in 1983, where empty CDs were used to selectively remove toxic retionoids from the circulation in A vitamin intoxication.<br/>Based on this recognition, AKZO-Organon initiated a program aiming at selective removal of neuromuscular blocking agent during anesthesia using a taylor-made CD that binds target API. These efforts resulted in the approval of a uniquely modified gammaCD nano-cavity. The fist cyclodextrin as a drug, a selective binding agent was marketed recently in USA, EU and Japan (Bridion® by Merck, Co.)<br/>The safe and potent solubilizing excipient, 2-hydroxypropyl-b-CD (HPBCD) listed in both the US and EU Pharmacopoeias, has an Orphan Drug designation, due to its selective cholesterol binding property. It has been established that HPBCD improves the clinical status of patients suffering from a deadly lysosomal storage disease, called Nieman-Pick-Type C (NPC). Soon, after clinical trials, in 2010, first US FDA, later EU granted Orphan drug designation for HPBCD to treat NPC. Currently more than 30 patients world-wide are treated using this cyclodextrin derivative with promising results. Similar lipid complexing properties were recently used to apply HPBCD as a lead drug candidate for two orphan kidney indications (Focal Segmental Glomerulosclerosis and Alport Syndrome) by Variant Pharmaceuticals. A number of further therapeutic applications of CDs themselves are expected to come.<br/>A unique, diagnostic application of a CD has been developed and the method marketed by Oxford Nanopore Ltd for automatized DNA sequencing. A bacterial protein nanopore is combined with CD as analyte-recognizing adapter sensor. This enables quick, reliable and cheap DNA sequencing. The devices named MinON®, SmigdION® are currently in practical use.

Cyclodextrins from toy to tool: Excipients and therapeutic agents

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.