Case Study With Chloroquine And Hydroxychloroquine By Using A Thermal Aerosolization Process Coupled To Super Sesi-Hrms

T. Zivkovic Semren, M. Fatarova,S. Majeed,A. R. Kolli, A. Mazurov,F. Martin,A. Kuczaj,J. Hoeng,M. C. Peitsch,N. Ivanov, P. A. Guy

INTERNATIONAL JOURNAL OF TOXICOLOGY(2021)

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摘要
Severe acute respiratory syndrome coronavirus 2 was identified in January 2020 as the cause of the SARS-like atypical pneumonia called coronavirus disease 2019 Recent publications have brought attention to the possible benefit of chloroquine (CQ) and its analog hydroxychloroquine (HCQ) in treatment of patients infected by this coronavirus Previous research has demonstrated a narrow margin between the therapeutic and toxic doses of CQ and HCQ In this study, we investigated the feasibility of developing inhalable forms of the antiviral drugs CQ and HCQ The drugs were solubilized in an appropriate carrier and subjected to thermal aerosolization to generate an aerosol The liquid formulation was evaporated by heating and subsequently cooled, which triggered nucleation and condensation processes that lead to aerosol formation The aerosol was generated and assessed by using a programmable dual syringe pump coupled to the aerosol generation device, which guaranteed active drawing of a specified volume of air The chemicals were detected by using secondary electrospray ionization interfaced with a Q Exactive mass spectrometer (MS) Transfer rate was assessed by analyzing the chemicals present in aerosol particles trapped in a Cambridge filter pad, by using liquid chromatography coupled to MS detection Both CQ and HCQ solutions showed good potential for thermal aerosolization These formulations are currently undergoing further improvements in parallel with transfer rate optimization related to thermal aerosol generation and gas/liquid phase partitioning The developed methods and protocol for thermal drug aerosolization could have potential applications in treatment of infected people
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