Abstract
Dry powder inhalers (DPIs) provide an effective route for pulmonary drug delivery, enabling localized treatment of respiratory infections while reducing systemic exposure. Levofloxacin, a second-generation fluoroquinolone antibiotic, is widely used in the management of bacterial lung infections and represents a promising candidate for inhalation therapy. In carrier-based DPI formulations, lactose monohydrate is commonly employed to enhance powder flowability, improve dose uniformity, and facilitate drug dispersion during inhalation.
The present study aimed to assess the in vitro aerosolization behavior and deposition characteristics of binary powder mixtures composed of levofloxacin and lactose intended for pulmonary administration. Powder blends were prepared using geometric mixing at a drug-to-carrier ratio of 2:1 (w/w) to ensure adequate homogeneity. The resulting formulations were filled into hard gelatin capsules and tested using a Cyclohaler® dry powder inhaler.
The aerodynamic properties of the powders were investigated using a Next Generation Impactor (NGI), which enabled evaluation of particle deposition patterns across impactor stages corresponding to different aerodynamic particle sizes under controlled airflow conditions simulating various inspiratory efforts. The emitted dose was determined using a Dosage Unit Sampling Apparatus (DUSA). Quantitative determination of levofloxacin deposited on each NGI stage was performed using a validated ultra-performance liquid chromatography (UPLC) method.
The investigated formulations exhibited stable and reproducible emission from the inhaler device. The emitted dose exceeded 70% of the nominal dose, indicating efficient release of the powder from the capsules. The fine particle dose remained above 25%, demonstrating the formation of respirable particles capable of reaching the lower regions of the lungs. Higher airflow rates resulted in enhanced powder dispersion and improved aerosolization efficiency, leading to increased drug deposition within NGI stages corresponding to aerodynamic particle sizes below 5 µm.
Overall, the results indicate that lactose-based carrier systems provide suitable performance characteristics for levofloxacin dry powder inhalation formulations. The observed aerodynamic behavior and emission efficiency confirm the potential applicability of these binary mixtures for pulmonary drug delivery. Further optimization of formulation parameters may contribute to improved lung deposition and enhanced therapeutic outcomes in inhaled antibacterial therapy.
Funding: levofloxacin, dry powder inhaler, lactose carrier, pulmonary delivery, NGI
Funding: This research is funded by a research grant from the Medical Research Agency (ABM), Poland, under the National Recovery and Resilience Plan, project number KPOD.07.07-IW.07-0216/24.
Keywords: ciprofloxacin, lactose, dry powder inhaler, APSD, NGI
References:
1. Coates, M.S.; Chan, H.K.; Fletcher, D.F.; Raper, J.A. Influence of Air Flow on the Performance of a Dry Powder Inhaler Using Computational and Experimental Analyses. Pharm. Res. 2005, 22, 1445–1453.
- Shur, J.; Lee, S.; Adams, W.; Lionberger, R.; Tibbatts, J.; Price, R. Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers. AAPS J. 2012, 14, 667–676.
- Jõgi, R.; Mattila, L.; Vahteristo, M.; Takala, A.; Lähelmä, S.; Vartiainen, V.A.; Lindqvist, A. Inspiratory Flow Parameters through Dry Powder Inhalers in Healthy Volunteers and Patients with Chronic Obstructive Pulmonary Disease (COPD): Device Resistance Does Not Limit Use in COPD. Int. J. COPD 2021, 16, 1193–1201.
Biography:
Marta Mazurowska is a pharmacy student at the Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University in Toruń, Poland, and an emerging researcher in the field of pharmaceutical technology. Her work focuses on inhalation drug delivery systems, particularly the formulation and evaluation of dry powder inhalers containing antibacterial agents such as levofloxacin. She is involved in experimental studies related to capsule-based inhalation formulations and aerodynamic performance testing using cascade impactor methods. Her research interests include pulmonary drug delivery, inhalation formulation development, and advanced pharmaceutical dosage forms for respiratory therapy.