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

Mohammad Zaidur Rahman Sabuj; Md Abdur Rashid; Tim R Dargaville; Nazrul Islam

doi:10.3390/ph15101223

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

Pharmaceuticals (Basel). 2022 Oct 2;15(10):1223. doi: 10.3390/ph15101223.

Authors

Mohammad Zaidur Rahman Sabuj¹, Md Abdur Rashid², Tim R Dargaville³, Nazrul Islam^{1

4}

Affiliations

¹ Pharmacy Discipline, School of Clinical Sciences, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia.
² Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Aseer, Saudi Arabia.
³ Faculty of Science, School of Chemistry and Physics, Queensland University of Technology, Brisbane, QLD 4000, Australia.
⁴ Centre for Immunology and Infection Control (CIIC), Queensland University of Technology, Brisbane, QLD 4000, Australia.

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.

Keywords: ciprofloxacin; dry powder inhaler; inhalation formulation; nanoparticles; poly(2-ethyl-2-oxazoline); stability.

Grants and funding

This research was supported by Research Training Program (RTP) Scholarship to Mohammad Zaidur Rahman Sabuj granted by the Australian Government through Queensland University of Technology and King Khalid University through the grant number RGP-2/70/43.