Ann Med Med Res | Volume 2, Issue 1 | Research Article | Open Access

Cyclodextrin Affects Distinct Tissue Drug Disposition as a Novel Drug Delivery Vehicle

Ying Fei Li1, Yan Li1, Becky Reed2, Xiaole Shen3, Duxin Sun2 and Simon Zhou1*

1Translational Development and Clinical Pharmacology, Celgene Corporation, USA2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, USA3Formulation Development Drug Product Development, Celgene Corporation, Summit, USA

*Correspondance to: Simon Zhou 

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Introduction: Cyclodextrin is a novel solubilizing agent for parenteral administration of drugs with poor aqueous solubility, and it is commercially available as drug formulation excipient from different manufacturers. Its ability to dissolve drugs into stable aqueous solution in vitro and in vivo is well-established. However, tissue dispositions of drugs encapsulated in Cyclodextrin have not been extensively studied, and it is assumed to follow the same pattern of simple co-solvents. This study aims to assess the plasma and tissue drug disposition of Cyclodextrin by two different manufactures, in comparison to a liquid co-solvent formulation. Methods: Two Cyclodextrin formulations (Captisolor Dexolve) or a co-solvent formulation (free solution) of an investigational drug were subcutaneously or intravenously administered to 3 cohorts of normal mice. Following a single SQ/IV dose of 5 mg/kg of treatment, 10 organs as well as plasma and blood were collected at a serial of time points from 0.17 h to 24 h post dose. The total concentrations of investigational drug in all tissue specimens were measured with LC-MS/MS. Results: Compared to SQ administration of free solution, both Cyclodextrin formulations produced distinct tissue concentration-time profiles, and exposure (Cmax and AUC) of the investigational drug in most of measured tissues, except for blood and plasma, wherein all three treatments had similar concentration-time profiles. In addition the pattern of drug tissue exposure over time by Captisol was drastically different from that of Dexolve, especially in the bone and fat pat. Such difference was more pronounced following SQ administration than IV administration, suggesting a firstpass filtering effect of the Cyclodextrin formulations. Furthermore, our analysis also showed that predominate driver for drug tissue distribution is the Cyclodextrin-drug complex and free drug, for the two Cyclodextrin formulations and free solution, respectively. Conclusion: In addition to improving the solubility of the poorly soluble drugs, the Cyclodextrin formulations alter the drug position in tissue, which is largely governed by the interplay between the Cyclodextrin and the drug, and subsequently the uptake of Cyclodextrin-drug complex in tissue. The distinct tissue distribution of Cyclodextrin drug complex, but similar plasma total drug exposure challenges the traditional bioequivalence concept based on similar plasma drug exposure, calling for direct drug measurement in target organs for equivalence assessment.


Cyclodextrin; Parenteral formulation; Bioavailability; Bioequivalence; Drug carrier


Fei Li Y, Li Y, Reed B, Shen X, Sun D, Zhou S. Cyclodextrin Affects Distinct Tissue Drug Disposition as a Novel Drug Delivery Vehicle. Ann Med Medical Res. 2019; 2: 1021. .

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