New chromatographic insights on drug:cyclodextrin inclusion complexes and their potential use in drug delivery

ABSTRACT

Objectives

Cyclodextrins (CDs) play a pivotal role in the controlled release of drugs; however, their ability to gradually release drugs is here interrogated: can cyclodextrins, even those that form strong inclusion complexes, sustain a prolonged release of drugs?

Methods

An original chromatographic approach was developed and accordingly we classified and determined drugs that form the most stable inclusion complexes with cyclodextrins. β-CD and hydroxypropyl-β-CD (HP-β-CD) were coupled to pullulan (Pul) microspheres and packed into a chromatographic column. Then, different drugs or model compounds were eluted, and values of the retention time (RT) were determined. In vitro release studies were performed for drugs that form the most stable inclusion complexes.

Results

The drugs with the longest RT value form the most stable inclusion complexes with Pul/β-CD and Pul/HP-β-CD microspheres. Pul/β-CD microspheres form more stable inclusion complexes than Pul/HP-β-CD microspheres. However, in spite of their high stability, they were not able to gradually release the included drug (15 min release time). The cross-chromatographic experiments confirmed the hypothesis that in aqueous solution, drug/cyclodextrin complexes are continuously associated and dissociated.

Conclusions

If the dissociation of the guest molecule is very rapid, why is it expected that these complexes gradually release the drug?

KEYWORDS:

• Β-cyclodextrin
• drug delivery
• hydroxypropyl-β-cyclodextrin
• inclusion complex
• liquid chromatography

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception and design: G Fundueanu. Analysis and interpretation of data: M Constantin, B Cosman, G Fundueanu. Drafting of the paper: Marieta Constantin, G Fundueanu. Revising of the paper, final approval of the version to be published, agree to be accountable for all aspects of the work: All authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by a grant of the the Ministry of Research, Innovation and Digitization, CNCS/CCCDI-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0050, within PNCDI III.