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