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.
Highlights
Pharmaceutical excipients are defined as any substance in drugs possessing pharmacological inertia, except for active pharmaceutical ingredients (API)
A specific and accurate Liquid chromatography–Mass spectrometry (LC-MS)/MS approach was developed for the quantitative measurement of dextromethorphan hydrobromide and β-CD
The results showed that the effect of inclusion compounds changed the biological process, elimination rate, and exposure amount of β-CD and dextromethorphan hydrobromide in vivo
Summary
Pharmaceutical excipients are defined as any substance in drugs possessing pharmacological inertia, except for active pharmaceutical ingredients (API). Excipients can influence the absorption, distribution, metabolism, and elimination process (ADME) of drugs administered jointly, and can improve oral bioavailability by controlling drug dissolubility or penetrability [2]. Studies have shown that it is necessary to check the quality and performance of excipients, as well as their safety in vivo [5,6]. HP-β-CD is used for injection administration, but its analogue, β-cyclodextrin (β-CD), can only be used for oral administration; whether β-CD could have similar or opposing behavior in vivo relative to HP-β-CD, especially regarding its influence on API absorption, was the primary purpose of this study
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