Nanoporous mannitol carrier prepared by non-organic solvent spray drying technique to enhance the aerosolization performance for dry powder inhalation

Tingting Peng,Qiuying Liao,Jing Xu,Ying Huang,Chuan-Yu Wu,Chuanbin Wu,Ziyu Zhao,Zhengwei Huang,Xin Pan,Xuejuan Zhang,Jiwen Zhang

doi:10.1038/srep46517

Abstract

An optimum carrier rugosity is essential to achieve a satisfying drug deposition efficiency for the carrier based dry powder inhalation (DPI). Therefore, a non-organic spray drying technique was firstly used to prepare nanoporous mannitol with small asperities to enhance the DPI aerosolization performance. Ammonium carbonate was used as a pore-forming agent since it decomposed with volatile during preparation. It was found that only the porous structure, and hence the specific surface area and carrier density were changed at different ammonium carbonate concentration. Furthermore, the carrier density was used as an indication of porosity to correlate with drug aerosolization. A good correlation between the carrier density and fine particle fraction (FPF) (r2 = 0.9579) was established, suggesting that the deposition efficiency increased with the decreased carrier density. Nanoporous mannitol with a mean pore size of about 6 nm exhibited 0.24-fold carrier density while 2.16-fold FPF value of the non-porous mannitol. The enhanced deposition efficiency was further confirmed from the pharmacokinetic studies since the nanoporous mannitol exhibited a significantly higher AUC0-8h value than the non-porous mannitol and commercial product Pulmicort. Therefore, surface modification by preparing nanoporous carrier through non-organic spray drying showed to be a facile approach to enhance the DPI aerosolization performance.

Highlights

An optimum carrier rugosity is essential to achieve a satisfying drug deposition efficiency for the carrier based dry powder inhalation (DPI)
The local delivery of drug to the lung can be achieved by using nebulizers, pressurized meter dose inhalers, or dry powder inhalers (DPIs)
For this non-organic solvent spray drying technique, the outlet temperature and the concentration of ammonium carbonate were shown to be key factors influencing the pore formation of mannitols

Summary

Introduction

An optimum carrier rugosity is essential to achieve a satisfying drug deposition efficiency for the carrier based dry powder inhalation (DPI). As the surface roughness largely affects particle-particle interactions and aerosolization performance, different attempts to modify the surface roughness of carrier particles to achieve lower adhesion forces and improved inhalation performance were reported These attempts mainly include particle crystallization with different solvents[6], adding fine particles to alter the surface roughness by occupying the active sites[7], particle milling with different time and material[8], polymer coating of particles[9], and spray drying at different drying conditions[10]. The common characteristic lying behind the documented methods was to design carriers with small surface asperities Carrier with such a microstructure meets the requirements for powder particles used in inhalation systems, since it can reduce drug-carrier adhesion forces and ease drug re-entrainment from carriers to allow for tiny airway deposition. Nanoporous carrier was exploited to enhance drug deposition efficiency and attain better aerosolization performance by constructing small surface asperities through the nano-metered pores

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Conclusion