A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation

Abstract

Inhaled drug delivery is a promising approach to achieving high lung drug concentrations to facilitate efficient treatment of tuberculosis (TB) and to reduce the overall duration of treatment. Rifampicin is a good candidate for delivery via the pulmonary route. There have been no clinical studies yet at relevant inhaled doses despite the numerous studies investigating its formulation and preclinical properties for pulmonary delivery. This review discusses the clinical implications of pulmonary drug delivery in TB treatment, the drug delivery systems reported for pulmonary delivery of rifampicin, animal models, and the animal studies on inhaled rifampicin formulations, and the research gaps hindering the transition from preclinical development to clinical investigation. A review of reports in the literature suggested there have been minimal attempts to test inhaled formulations of rifampicin in laboratory animals at relevant high doses and there is a lack of appropriate studies in animal models. Published studies have reported testing only low doses (≤ 20 mg/kg) of rifampicin, and none of the studies has investigated the safety of inhaled rifampicin after repeated administration. Preclinical evaluations of inhaled anti-TB drugs, such as rifampicin, should include high-dose formulations in preclinical models, determined based on allometric conversions, for relevant high-dose anti-TB therapy in humans. Graphical abstract

Development of natural polymers-based inhaled microspheres for tuberculosis

“…Several anti-TB drugs have been researched for their inhalable formulation using in vitro and in vivo studies. These studies inform that inhaled drugs for TB treatment assure therapeutic benefits by delivering drugs directly to the lungs at higher concentrations (Khadka et al, 2022).…”

“…TB therapy is recommended with regimens of four anti-TB first-line drugs for six months, which are isoniazid (INH), rifampin (RIF), ethambutol (ETH), and pyrazinamide (PZA) (Khadka et al, 2022). They are prescribed during the first two months of treatment and continued for the next four months with rifampicin and isoniazid only.…”

Proposing Intranasal Rifampin for Alzheimer’s Disease and the Other Age-Related Neurodegenerative Proteinopathies

“…By 1968, it was clear that rifampin had an important role in therapy for mycobacterial infections [12]. Rifampin is delivered orally [15.16], intravenously [16], topically [17], by inhalation for pulmonary mycobacterial infection [18,19], as eye drops [20] and as nose drops [21,22].…”

Liposomal Forms of Fluoroquinolones and Antifibrotics Decorated with Mannosylated Chitosan for Inhalation Drug Delivery

“…Recently several papers were published devoted to the inhaled liposomal form of some antituberculosis drugs such as rifampicin [17,18]. An in vivo test with small animals reported that almost 65% of the dose was achieved in the lungs.…”