ABSTRACT

Introduction: Drug particles inhaled via the respiratory system must first dissolve in the respiratory tract lining fluid (RTLF) that lies on the surfaces of airways and alveoli, so that they are absorbed and have therapeutic action. Artificial simulated RTLFs are often used for in vitro dissolution studies to determine the solubility and dissolution of inhaled drug particles. Such studies can be used to predict bioavailability minimizing the requirement for in vivo studies. Numerous studies have been conducted to develop bio-relevant simulated RTLFs; however, to date, there is no singular simulated RTLF that closely resembles human RTLF.

Areas covered: This review focuses on the composition of natural and simulated RTLFs and their use in in vitro dissolution studies.

Expert opinion: There is variation in the composition and thickness of RTLF along the respiratory tract. Identification of the actual concentration of components of endogenous RTLF present in different areas of the respiratory tract helps in the development of region-specific simulated RTLFs. It is recommended that region-specific simulated RTLFs can be prepared by varying concentration of major RTLF components like mucus/gel simulants, lipids/surfactants, peptides/proteins, and inorganic/organic salts.

摘要

简介：通过呼吸系统吸入的药物颗粒，必须首先溶解在位于气道和肺泡表面的呼吸道衬里液（RTLF）中，才能被吸收并发挥治疗作用。人工模拟 RTLF 通常用于体外溶出度研究，以确定吸入药物颗粒的溶解度和溶出度。此类研究可用于预测生物利用度，从而最大限度地减少对体内研究的需求。已经进行了大量研究来开发与生物相关的模拟 RTLF；然而，迄今为止，还没有与人类 RTLF 非常相似的单一模拟 RTLF。

涵盖的领域：本综述侧重于天然和模拟 RTLF 的组成及其在体外溶出度研究中的应用。

专家意见：沿呼吸道的 RTLF 成分和厚度存在差异。确定存在于呼吸道不同区域的内源性 RTLF 成分的实际浓度有助于开发特定区域的模拟 RTLF。建议可以通过不同浓度的主要 RTLF 成分（如粘液/凝胶模拟物、脂质/表面活性剂、肽/蛋白质和无机/有机盐）来制备特定于区域的模拟 RTLF。