Simulation of respiratory tract lining fluid for in vitro dissolution study.

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.