Improving oral delivery of ciprofloxacin through in situ spray drying and acid counterions

This study explores the application of a novel three-fluid nozzle spray drying technique in formulating in situ ciprofloxacin (CFX) salts for improved oral drug delivery. The used key materials in the study include CFX combined with four different counterions: succinic acid (SA), glutaric acid (GA), adipic acid (AA), and pimelic acid (PA), alongside hydroxypropyl methylcellulose (HPMC) as a matrix agent. The process utilized a three-fluid nozzle spray drying technique to produce CFX salts directly with these acids during the process, creating three types of formulations: pure salts (SALT), solutions of drug and polymer (SOL), and nanoprecipitates of drug within a polymer matrix (SUS). Powder X-ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM) analyses revealed that the formulations predominantly exhibited an amorphous structure with varied particle shapes and sizes. The dissolution profiles of CFX salts show a marked burst release within the initial 5 min, with CFX-GA leading at nearly double the release rate of CFX-AA, after which all formulations rapidly achieve over 90 % dissolution and maintain a stable release up to 30 min. This pattern was attributed to the interactions between the drug salts and HPMC, resulting in a sustained release of CFX. In vivo experiments with rabbits revealed a higher plasma concentration of CFX for CGAH-sus compared to CGAH-sol, highlighting the enhanced bioavailability of the SUS formulation. The amorphous nature of CGAH-sus, with ionization confirmed through Raman spectroscopy, facilitated efficient drug release and absorption in the gastrointestinal tract. This study illustrates the effectiveness of the three-fluid nozzle spray drying method in producing salts with varied physical properties and dissolution profiles, holding potential for advanced oral drug delivery systems.