Optimization and Application of an Efficient and Stable Inhalation Exposure System for Rodents

Area of Science:

• Pharmaceutical Science
• Respiratory Medicine
• Toxicology

Background:

• Inhalation drug delivery is a complex but promising method in pharmaceutical research.
• Establishing stable aerosol environments for dynamic inhalation administration presents significant challenges.
• Indacaterol glycopyrronium bromide (IM/GP) mixed powder is a key treatment for chronic obstructive pulmonary disease (COPD).

Purpose of the Study:

• To develop optimized inhalation conditions for IM/GP mixed powder.
• To assess the pulmonary safety and potential toxicity of IM/GP mixed powder in Sprague-Dawley (SD) rats following inhalation exposure.

Main Methods:

• Coordinated control of atomization flow, air pump flow, and scraper speed to stabilize aerosols at 200 ± 20% mg/m³.
• Nose-only administration of IM/GP mixed powder, Ultibro, and a control (lactose-magnesium stearate) to SD rats at 2.6 mg/kg/day for 14 days, followed by a 14-day recovery period.
• Evaluation of hematology, inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and serum, and histopathological examinations.

Main Results:

• Stable powder aerosols were achieved with specific flow rates (atomization: 10 L/min, sampling: 2 L/min, system pumping: 10 L/min) and scraper speed (8-10 L/min).
• No significant adverse effects were observed in body weight, clinical signs, hematology, or pathology in rats exposed to IM/GP mixed powder.
• Pulmonary safety was confirmed at the target dose and aerosol concentration.

Conclusions:

• The study successfully established reproducible inhalation conditions for IM/GP mixed powder.
• IM/GP mixed powder inhalation at 2.6 mg/kg/day, under the specified aerosol concentration, demonstrated no pulmonary toxicity in SD rats.
• The findings support the safe use of IM/GP mixed powder via inhalation for COPD treatment.