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.

中文翻译：

---

设计含有依维莫司的口分散膜，以提高顺应性和生物利用度

摘要

介绍

依维莫司（EVR）已被批准用于治疗各种晚期癌症，其适应症也在不断扩大。因此，对于吞咽困难的患者，例如小儿和老年患者，获得方便的制剂至关重要。由于EVR在水中的溶解度低，通过CYP3A4酶引起的肠道代谢，P-gp介导的外排以及肝脏中的代谢，因此其口服吸收受到限制。这项研究的目的是开发一种新型的舌下含口腔分散膜的依维莫司，可改善患者的依从性并增强EVR的口服生物利用度。

研究设计与方法

负载EVR的舌下口腔分散膜通过溶剂流延法制备，并通过体外和体内研究进行评估。

结果

膜的性质通过扫描电子显微镜，差示扫描量热法，X射线衍射和傅里叶变换红外光谱法测定。相思树胶的添加对于保护药物免受氧化至关重要。药代动力学研究表明，加载到舌下口腔分散膜中可显着提高EVR的口服生物利用度。

结论

加载EVR的舌下口腔分散性薄膜是一种有前途，经济且方便的方法，可以以固体剂型有效地递送EVR。