The Biological Fate of Pharmaceutical Excipient beta-Cyclodextrin: Pharmacokinetics, Tissue Distribution, Excretion, and Metabolism of beta-Cyclodextrin in Rats

beta-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing drug stability. As a bioactive molecule, the metabolism of beta-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of beta-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient beta-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of beta-cyclodextrin after oral administration in rats. Results showed that beta-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of beta-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact beta-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that beta-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO2 and H2O. Results proved that beta-cyclodextrin, with relative low accumulation in the body, had good safety. The results will assist further study of the design and safety evaluation of adjuvant beta-cyclodextrin and promote its clinical development.