Abstract
Levofloxacin is a fluoroquinolone antibiotic widely used in the treatment of respiratory tract infections and represents a promising candidate for pulmonary drug delivery. However, its crystalline structure and physicochemical properties may limit its aerosolization performance in dry powder inhalation systems. Hot-melt extrusion (HME) is an established pharmaceutical processing technique that enables the preparation of amorphous solid dispersions, thereby improving drug dispersion and modifying physicochemical properties relevant for inhalation delivery.
The aim of this study was to develop and evaluate levofloxacin-based solid dispersions prepared by hot-melt extrusion using selected pharmaceutical polymers intended for pulmonary administration. Binary systems consisting of levofloxacin and polymer carriers were processed using a twin-screw hot-melt extruder under controlled temperature conditions. The resulting extrudates were subsequently milled to obtain powders suitable for inhalation applications. The obtained formulations were filled into hard gelatin capsules and aerosolized using a Cyclohaler® dry powder inhaler.
Differential scanning calorimetry (DSC) was used to assess the thermal properties and physical state of levofloxacin within the polymer matrices. Thermal analysis demonstrated a significant reduction or complete disappearance of the characteristic melting peak of crystalline levofloxacin, indicating reduced crystallinity and the formation of amorphous or partially amorphous solid dispersions. These findings confirm effective incorporation of the drug into the polymer matrices during the extrusion process.
Aerodynamic performance was evaluated using a Next Generation Impactor (NGI) to determine the aerodynamic particle size distribution (APSD). The emitted dose (ED) was assessed using a Dosage Unit Sampling Apparatus (DUSA), while quantitative analysis of drug deposition was performed using validated chromatographic methods. The extruded and milled formulations demonstrated efficient aerosolization and reproducible emission from the inhaler device. The emitted dose exceeded 70% of the nominal dose, while the fine particle dose remained above 25%, confirming the generation of respirable particles suitable for pulmonary delivery. Improved aerosolization performance was observed at higher airflow rates, indicating effective powder dispersion.
The results demonstrate that hot-melt extrusion is a suitable technique for the preparation of levofloxacin solid dispersions intended for inhalation delivery. The combination of polymer carriers and extrusion processing enabled modification of the drug’s physicochemical properties and the production of powders with appropriate aerodynamic characteristics. These findings support the potential application of HME-based formulations in the development of advanced inhaled antibacterial therapies.
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: levofloxacin, hot-melt extrusion, solid dispersion, inhalation, APSD
References:
1. Alshetaili, A.; Alshahrani, S.M.; Almutairy, B.K.; Repka, M.A. Hot Melt Extrusion Processing Parameters Optimization. Processes 2020, 8, 1516.
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Biography:
Adam Sikora, PhD, is a pharmacist and senior researcher at the Department of Medicinal Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland. His research focuses on the development and physicochemical characterization of advanced drug delivery systems, with particular emphasis on dry powder inhalation formulations and polymer-based drug products prepared using hot-melt extrusion. His expertise includes solid-state characterization using thermal techniques such as differential scanning calorimetry, as well as advanced analytical methods, including LC–MS/MS and high-resolution mass spectrometry (IT-TOF), for qualitative and quantitative analysis of pharmaceutical compounds. He is actively involved in the aerodynamic evaluation of inhalation formulations and translational research aimed at improving the performance and manufacturability of inhaled medicines. His scientific interests include pulmonary drug delivery, pharmaceutical technology, and modern analytical techniques in drug development.