Design and evaluation of inhalable nanocrystals embedded microparticles with enhanced redispersibility and bioavailability for breviscapine

The purpose of this study was to design novel inhalable nanocrystals embedded microparticles for pulmonary delivery of breviscapine (BVC). The TPGS modified BVC nanocrystals (BVC-NC@TPGS) were fabricated by high pressure homogenization. And the BVC-NC@TPGS was further converted into nanocrystals-embedded microparticles (BVC-NEP) via spray-drying. The influence of matrix formers and concentration on the properties of BVC-NEP for inhalation was investigated. The particle size, morphology, drug crystal state, in vitro aerodynamic performance, in vitro release behavior and pharmacokinetic behaviors were characterized. It was demonstrated that the morphology, lung deposition as well as in vitro drug release from the microparticles were significantly influenced by matrix formers type and concentration. BVC-NEP with 10% TPGS as stabilizer and 200% MN as matrix formers presented the highest FPF value and most excellent flowability as well as redispersibility. Further the in vivo pharmacokinetic studies demonstrated that the AUC((0-infinity)) of the inhalable BVC-NEP/MN (1411.099 +/- 334.62 mu g/L h) was 6.29 times (p < 0.05) as high as that of the coarse BVC (224.21 +/- 59.47 mu g/L h), and not significantly from that of BVC injection. Therefore, inhalable nanocrystals-embedded microparticles could be a promising strategy for pulmonary delivery of poorly soluble drugs that was unfittable for oral administration. (C) 2020 Elsevier B.V. All rights reserved.