Micronization of ciprofloxacin by the Supercritical Antisolvent (SAS) Technique

Abstract

Ciprofloxacin is a broad-spectrum antibiotic that is proposed for pulmonary administration. In this work micronization of ciprofloxacin was performed by the Supercritical Antisolvent Technique (SAS) using ciprofloxacin base (CIP) in ethanol/acetic acid and ciprofloxacin hydrochloride salt (CIP·HCl) in methanol at 40–60 ºC and 100–150 bar. Yields ranged from 40 % to 90 %. CIP precipitated incorporating acetate whilst CIP·HCl precipitated as the AH1 anhydrous form. CIP and CIP·HCl particles exhibited an acicular morphology (0.2–0.9 μm wide × 1–4 μm long). Micronization adding lactose, PVP K-10 and K-30 modified the precipitate morphology. CIP·HCl:lactose and CIP·HCl:PVP K-30 at a 4:1 drug:excipient mass ratio precipitated like flakes. CIP·HCl:PVP K-10 precipitated as submicron globular particles suitable for oral formulation. Increasing the PVP content, the morphology changed to sheets and flakes, which could be used for pulmonary administration. The antibacterial activity of the samples for Staphylococcus epidermidis was confirmed. • CIP and CIP·HCl have been micronized by SAS at 40–60 ºC and 100–150 bar. • The crystal structure of SAS samples changed compared to the starting material. • CIP and CIP·HCl SAS samples show an acicular morphology (1–4 μm long). • Addition of excipients (lactose or PVP) led to flakes, sheets or globular particles. • The antibacterial activity of the SAS samples was confirmed.