Stability of Inhaled Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticle Dry Powder Inhaler Formulation in High Stressed Conditions

Abstract

In this study, the stability of ciprofloxacin (CIP)-loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) was investigated at normal and high stressed conditions. The blank NPs were used to understand the intrinsic physicochemical properties of the polymer NPs under these storage conditions. The formulated NPs were prepared by a coassembly reaction and dried by lyophilization. The powder NPs were stored at controlled room temperature (25 °C) with normal relative humidity (RH) (43%) and high temperature (40 °C) and RH (75%). The stored samples were analyzed by determining the particle sizes, morphology, solid-state properties, thermal behavior, drug-polymer interactions, and aerosol performances over six months. The chemical stability of the formulations was determined by X-ray diffraction, attenuated total refection-Fourier transform infrared (ATR-FTIR), and high-performance liquid chromatography (HPLC) over six months under both conditions. The particle size of the blank PEtOx NPs significantly (p < 0.05) increased from 195.4 nm to 202.7 nm after 3 months at 40 °C/75% RH due to the moisture absorption from high RH; however, no significant increase was observed afterward. On the other hand, the sizes of CIP-loaded PEtOx NPs significantly (p < 0.05) reduced from 200.2 nm to 126.3 nm after 6 months at 40 °C/75% RH. In addition, the scanning electron microscopy (SEM) images revealed that the surfaces of CIP-loaded PEtOx NPs become smoother after 3 months of storage due to the decay of surface drugs compared to the freshly prepared NPs. However, transmission electron microscopy (TEM) images could not provide much information on drug decay from the nanoparticle’s surfaces. The fine particle fraction (FPF) of CIP-loaded PEtOx NPs dropped significantly (p < 0.05) after three months at 25 °C/43% RH and 40 °C/75% RH conditions. The reduced FPF of CIP-loaded PEtOx NPs occurred due to the drug decay from the polymeric surface and blank PEtOx NPs due to the aggregations of the NPs at high temperatures and RH. Although the aerosolization properties of the prepared CIP-loaded PEtOx NPs were reduced, all formulations were chemically stable in the experimental conditions.

Investigation of Physico-Chemical Stability and Aerodynamic Properties of Novel “Nano-in-Micro” Structured Dry Powder Inhaler System

“…Throughout the testing period, they showed no signs of aggregation. A slightly rougher surface can be observed because the humidity caused moisture absorption [ 60 ]. The results of the laser diffraction method were similar to the results of the ImageJ 1.53e software, which was utilized to determine the particle size based on the pictures ( Table 4 ).…”

“…Throughout the testing period, they showed no signs of aggregation. A slightly rougher surface can be observed because the humidity caused moisture absorption [60].…”

Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide

“…The formulations were also studied to determine the drug-loading and drug-release characteristics of the PEtOx polymer. We have recently investigated the stability of the CIP-loaded PEtOx NPs DPI formulation in highly stressed conditions [43]. In this present study, the bactericidal effects of the formulated CIP-loaded PEtOx NPs were determined compared to free CIP against S. aureus and P. aeruginosa.…”

High-resolution short-term prediction of the COVID-19 epidemic based on spatial-temporal model modified by historical meteorological data

“…Studies have also confirmed the important role of sewer transmission due to fecal aerosols in community outbreaks through case-by-case analysis [27] . Since polymeric aerosols undergo a decay process differing from the general composition of pollution gases [28] , research simulated the diffusion transport process of solid-liquid droplets in an outdoor environment by CFD to demonstrate that droplet transmission of virus-carrying droplets can lead to the outdoor spread of respiratory infections [29] . Under the influence of boundary layer turbulence characteristics and meteorological processes, their concentrations of droplets exhibit complex spatial and temporal distributions.…”