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

Abstract

β-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 β-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of β-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient β-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of β-cyclodextrin after oral administration in rats. Results showed that β-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of β-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact β-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that β-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO2 and H2O. Results proved that β-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 β-cyclodextrin and promote its clinical development.

A rotaxane-based platform for tailoring the pharmacokinetics of cancer-targeted radiotracers

“…Experiments reported that a fraction between 10% and 20% of administered β-CD is digested in the small intestine after 24 h. 63,64 Major degradation of β-CD occurs in the microflora of the intestine or colon. 55,64 β-CD also showed a trend towards renal enrichment, 55 . We thank all members of the Holland group for helpful discussions and continuous support.…”

“…49,50 Further hydrolysis results in smaller molecules, mainly maltotriose, maltose, and glucose, which are eventually absorbed and metabolised into CO 2 and H 2 O. [51][52][53][54][55] Known CD-hydrolysing enzymes include cyclomaltodextrinases and a-amylases. 49,50 Chemical conditions, including low pH with Brønsted acids, or the use of Lewis acids, were also reported to catalyse the hydrolytic ring-opening of CDs.…”

“…[56][57][58] The three most common cyclodextrins, a-CD (n = 6 glucose monomers), b-CD (n = 7), and g-CD (n = 8) were found to display different rates of degradation when exposed to gastric acid, or amylases from saliva or pancreatic tissue in vivo. 55,[59][60][61][62] While a-CD displays resistance and negligible degradation, and g-CD is essentially completely digested in the small intestine, b-CD (as employed in our radiotracer design for [ 89 Zr]ZrFe-2) follows an intermediate degradation pathway. Experiments reported that a fraction between 10% and 20% of administered b-CD is digested in the small intestine aer 24 h. 63,64 Major degradation of b-CD occurs in the micro-ora of the intestine or colon.…”

Cyclodextrin nanoparticles for diagnosis and potential cancer therapy: A systematic review

“…Cyclodextrins are generally not metabolizable by gastric acids or amylase. When CDs are administered orally, it was observed that CDs rapidly hydrolyze in the intestine and get excreted via feces ( Mu et al, 2022 ). While in parenteral administration, the primary excretion of CDs occurs via urine ( Loftsson et al, 2016 ).…”

Strategic developments in the drug delivery of natural product dihydromyricetin: applications, prospects, and challenges

“…Therefore, inclusion technology may be an effective strategy to improve the low water solubility of DHM. Particularly, the hydroxypropyl-β-cyclodextrin (HP-β-CD) not only has the good properties of β-cyclodextrin (β-CD) such as low price and good safety but also has the characteristics of biodegradability and high solubility (Mu et al., 2022 ). Ruan et al.…”