کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
237524 465711 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Optimizing aerosolization efficiency of dry-powder aggregates of thermally-sensitive polymeric nanoparticles produced by spray-freeze-drying
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی مهندسی شیمی (عمومی)
پیش نمایش صفحه اول مقاله
Optimizing aerosolization efficiency of dry-powder aggregates of thermally-sensitive polymeric nanoparticles produced by spray-freeze-drying
چکیده انگلیسی

Dry powder inhaler (DPI) delivery of therapeutic nanoparticles requires the nanoparticles to be transformed into inhalable micro-scale aggregate structures (i.e. nano-aggregates). The present work details the spray-freeze-drying (SFD) production of dry-powder aggregates of thermally-sensitive polymeric nanoparticles. Specifically, the aim is to optimize the aerosolization efficiency of the nano-aggregates, while keeping the morphology, production yield, flowability, and aqueous reconstitution in the desirable range. For this purpose, the effects of SFD process parameters (i.e. atomization rate, feed concentration, and feed rate) and freeze-drying adjuvant formulation on the nano-aggregate characteristics are examined. Low melting-point poly (caprolactone) (PCL) nanoparticles are used as the model nanoparticles. Mannitol and leucine are used as the hydrophilic and hydrophobic adjuvants, respectively. Large spherical porous nano-aggregates, where PCL nanoparticles are physically dispersed in the porous adjuvant matrix, have been produced. The presence of mannitol is crucial in ensuring that the nano-aggregates readily reconstitute into individual nanoparticles upon exposure to an aqueous environment, so that they can perform their intended therapeutic functions. The presence of leucine, on the other hand, is mandatory to obtain high aerosolization efficiency as its presence reduces the nano-aggregate tendency to agglomerate. At the optimal condition, nano-aggregates exhibiting ED (Emitted Dose) ≈ 95%, FPF (Fine Particle Fraction) ≈ 30%, and MMAD (Mass Median Aerodynamic Diameter) ≈ 5.3 μm, which are comparable to the values obtained in commercial DPI, have been produced. The results signify the potential of SFD to be employed in the production of inhalable dosage form of thermally-sensitive therapeutic nanoparticles.

Inhalable dry-powder aggregates of thermally-sensitive nanoparticle are produced by spray freeze drying. The influences of drying parameters and adjuvant formulation on particle morphology, flowability, production yield, aqueous reconstitution, and aerosolization efficiency are examined.Figure optionsDownload as PowerPoint slideHighlights
► Feed concentration, atomization rate are important spray-freeze-drying parameters.
► Mannitol to leucine ratio, not morphology, governs aerosolization efficiency.
► Spray-freeze-dried nano-aggregates can be aerosolized without carrier particles.
► Leucine increases fine particle fraction by reducing interparticle agglomeration.
► High fine particle fractions comparable to commercial DPI are obtained.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Powder Technology - Volume 214, Issue 1, 25 November 2011, Pages 169–176
نویسندگان
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