Designing orodispersible films containing everolimus for enhanced compliance and bioavailability

ABSTRACT

Introduction

Everolimus (EVR) has been approved for the treatment of various advanced cancers and its indications are increasingly expanding. Therefore, it is crucial for patients who have difficulty in swallowing, such as pediatric and elderly patients, to obtain a convenient formulation. The oral absorption of EVR is limited due to its low solubility in water, intestinal metabolism by CYP3A4 enzyme, P-gp-mediated efflux, and metabolism in the liver. The aim of this study was to develop a novel sublingual orodispersible film loading everolimus for improving patient compliance and enhancing oral bioavailability of EVR.

Research design and methods

Sublingual orodispersible films loading EVR were prepared by the solvent casting method and evaluated by in vitro and in vivo studies.

Results

The properties of films were determined by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectrometry. The addition of acacia gum appeared to be crucial for protecting the drug from oxidation. Pharmacokinetic studies showed that loading into the sublingual orodispersible films significantly increased the oral bioavailability of EVR.

Conclusion

The EVR-loaded sublingual orodispersible films are a promising, economical, and convenient approach for delivering EVR efficiently in a solid dosage form.

KEYWORDS:

• Acacia gum
• everolimus
• orodispersible film
• oral bioavailability
• patient compliance
• stability

Author contributions

Y Ma was involved in the preparation and characterization of sublingual orodispersible film loading everolimus, in vitro and in vivo studies of formulations and writing of the manuscript. R Guan was involved in drawing of graphs and analysis of data. S Gao was involved in the in vivo evaluation of formulations. W Song was involved in the checking and correction of language. Y Liu was involved in the breeding and care of laboratory animals. H Liu and Y Yang were involved in the design, and 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

Additional information

Funding

This paper was not funded.