The College of Pharmacy discussed the PhD dissertation entitled “Preparation and In Vitro/In Vivo Evaluation of Bromhexine Hydrochloride Loaded Nanomicelles for Nebulized Pulmonary Delivery”, by the student Hayder Imad Jabar and the supervisor, Professor Dr. Mowafaq Mohammed Ghareeb, at the Pharmaceutics Department.
The study aimed to prepare and evaluate bromhexine hydrochloride-loaded mixed nanomicelles as a nebulizable pulmonary drug-delivery system to improve local pulmonary delivery and reduce unnecessary gastrointestinal and systemic exposure.
The study included the preparation of 27 nanomicelle and mixed-micelle dispersions by thin-film hydration using Soluplus, Tyloxapol, Tween 80, and TPGS; their optimization based on particle size, PDI, zeta potential, entrapment efficiency, and drug loading; characterization of the optimized formula by physicochemical, thermal, and morphological studies, in vitro release, and stability studies; aerosol performance evaluation using a Next Generation Impactor; and an in vivo pharmacokinetic and lung distribution study in mice with bioimaging and histopathological examination.
The results showed that the optimized formula (drug:Soluplus:Tyloxapol at a ratio of 1:10:5) exhibited a particle size of 71.96 nm and an entrapment efficiency of 97.90%, suitable aerosol performance (MMAD = 3.987 µm, FPF = 60.25%), and at a nebulized dose of 0.20 mg/kg (one tenth of the oral dose) achieved a markedly higher lung Cmax, prolonged the lung half-life to 20.5 h versus the oral route, raised the lung-targeting index from 1.13 to 3.61 with a relative lung bioavailability of 3646%, and showed predominant lung localization by bioimaging with confirmed initial biosafety on histopathology, in addition to a Level A in vitro–in vivo correlation.
The study recommended conducting long-term stability studies and scale-up studies assessing batch reproducibility, performing chronic inhalation studies in respiratory disease animal models for long-term pulmonary safety and extended mucolytic efficacy, carrying out deeper mechanistic studies on drug release, cellular uptake, and biodistribution of the carriers, and completing a comprehensive preclinical regulatory package including validated analytical procedures and GLP-compliant repeat-dose toxicity studies as a prelude to clinical trials.
