Chloramphenicol/sulfobutyl ether-β-cyclodextrin complexes in an ophthalmic delivery system: prolonged residence time and enhanced bioavailability in the conjunctival sac

ABSTRACT

Objective: Conventional chloramphenicol (CHL) eye drops are widely used anti-infection formulations for acute bacterial conjunctivitis. However, the therapeutic effects are limited by insufficient concentration in the conjunctival sac. Hence, the objective of this study is to formulate and develop novel CHL eye drops with improved topical concentrations by increasing the solubility and decreasing the transcorneal penetration.

Research design and methods: CHL was included in the sulfobutyl ether-β-cyclodextrin (SBE-β-CD) using the freeze-drying method. Eye drops containing CHL/SBE-β-CD complexes were prepared and evaluated for in vitro and in vivo studies.

Results: The formation of CHL/SBE-β-CD inclusion was confirmed by DSC, XRD, NMR, and SEM. The aqueous solubility of CHL was significantly enhanced, and the drug transcorneal penetration was inhibited after inclusion. The CHL/SBE-β-CD displayed sustained release profiles. The tear fluid elimination kinetic study showed that the CHL/SBE-β-CD eye drops had better ability to prolong the residence time, and significantly increase CHL concentration in the conjunctival sac. Besides, it was shown that CHL/SBE-β-CD eye drops were nonirritating to rabbits’ eyes.

Conclusions: The SBE-β-CD inclusions offer a potential alternative strategy for ocular administration of poorly water-soluble drugs in the conjunctival sac.

KEYWORDS:

• Chloramphenicol
• sulfobutyl ether-β-cyclodextrin
• ocular administration
• conjunctival sac
• inclusion complexes

Author contributions

Y Xu and C Zhang were involved in the preparation and characterization of CHL/SBE-β-CD inclusions, in vitro and in vivo studies of formulations, and writing of the manuscript.

X Zhu was involved in drawing of graphs and analysis of data.

X Wang was involved in the in vivo evaluation of formulations.

H Wang was involved in the breeding and care of laboratory animals.

G Hu was involved in the checking and correction of language.

Q Fu was involved in the design, and guidance of this study.

Z He was involved in the guidance of this study.

All authors agree to be accountable for all aspects of the work.

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.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was financially supported by the National Science and Technology Major Project (No. 2017ZX09101001), the National Nature Science Foundation of China (No. 81502993), the Nature Science Foundation of Liaoning Province (No. 20170540842), the Basic Research Projects of Universities of Liaoning Provincial Department of Education (2017LQN02), and the Science and Technology Innovation Projects for Young and Middle-aged Talents of Shenyang (RC180261).