Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pulmonary Medicine

Background:

• Multi-drug-resistant tuberculosis (MDR-TB) poses a significant global health challenge.
• Current MDR-TB treatment involves prolonged chemotherapy with second-line drugs like capreomycin, which have severe adverse effects.
• Capreomycin requires frequent intramuscular or intravenous administration, limiting patient compliance and increasing systemic toxicity risks.

Purpose of the Study:

• To develop an inhaled dry powder formulation of capreomycin for targeted pulmonary delivery.
• To optimize the formulation and spray-drying process for effective aerosolization and lung deposition.
• To evaluate the pharmacokinetic profile of inhaled capreomycin in a preclinical model.

Main Methods:

• Spray drying technique was employed to create capreomycin dry powder formulations.
• Sixteen different formulations were designed and evaluated.
• The optimal formulation was characterized by its mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF).
• Pharmacokinetic studies were conducted in mice following intratracheal administration.

Main Results:

• A formulation containing 25% capreomycin (w/w) spray-dried at 90 °C exhibited optimal performance (MMAD 3.38 μm, FPF ~65%).
• Intratracheal administration achieved lung drug concentrations approximately 8-fold higher than the minimum inhibitory concentration (MIC) for over 24 hours.
• Inhaled capreomycin demonstrated significantly higher area under the curve, slower clearance, and longer mean residence time in lungs and plasma compared to intravenous injection.

Conclusions:

• Inhaled dry powder capreomycin is a promising non-invasive alternative for MDR-TB treatment.
• Pulmonary delivery enhances lung drug exposure and potentially reduces systemic side effects.
• This novel delivery system warrants further investigation for clinical application in MDR-TB therapy.