Development of Co-Amorphous Systems for Inhalation Therapy-Part 2: In Silico Guided Co-Amorphous Rifampicin-Moxifloxacin and -Ethambutol Formulations.

ABSTRACT: Background/Objectives: Tuberculosis (TB) remains a global health challenge due to long treatment durations, poor adherence, and growing drug resistance. Inhalable co-amorphous systems (COAMS) offer a promising strategy for targeted pulmonary delivery of fixed-dose combinations, improving efficacy and reducing systemic side effects. Methods: Our in-house-developed machine learning (ML) tool identified two promising API-API combinations for TB therapy, rifampicin (RIF)-moxifloxacin (MOX) and RIF-ethambutol (ETH). Physiologically based pharmacokinetic (PBPK) modeling was used to estimate therapeutic lung doses of RIF, ETH, and MOX following oral administration. Predicted lung doses were translated into molar ratios, and COAMS of RIF-ETH and RIF-MOX at both model-predicted (1:1)

SUBMITTER: Frohlich E 

PROVIDER: S-EPMC12567144 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature