Development of an In Vitro System To Emulate an In Vivo Subcutaneous Environment: Small Molecule Drug Assessment

• DOI: 10.1021/acs.molpharmaceut.2c00490
• Publication Date: 2022-10-24T19:56:06Z
• Authors: Hao Lou; Michael J. Hageman
• Keywords: IVIVC; Bioequivalence

A reliable in vitro system can support and guide the development of subcutaneous (SC) drug products. Although several systems have been developed, they some limitations, which may hinder them from getting more engaged SC product development. This study sought to develop a novel system, namely, Emulator SubCutaneous Absorption Release (ESCAR), better emulate vivo environment predict fate drugs delivery. ESCAR was designed using computer-aided design (CAD) software fabricated three-dimensional (3D) printing technique. has two acceptor chambers representing blood uptake pathway lymphatic pathway, respectively, although only investigated for small molecules this study. Via conducting DoE factor screening acetaminophen solution, relationship output (drug release "SC" chamber "blood circulation" chamber) input parameters could be modeled variety methods, including polynomial equations, machine learning Monte Carlo simulation-based methods. The results suggested that hyaluronic acid (HA) concentration critical parameter, whereas influence injection volume position not substantial. An vitro-in correlation (IVIVC) developed griseofulvin suspension explore feasibility applying formulation bioequivalence studies. LEVEL IVIVC model demonstrated PK profile correlated with profile. Therefore, model, new formulations, studies need conducted ESCAR, might waived. In conclusion, had important implications research quality control Future work would focused on further optimizing expanding its applications via assessing types formulations.