In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug

Changzhi Shi, Jelisaveta Ignjatović, Tingting Liu, Meihua Han, Dongmei Cun, Jelena Đuriš, Mingshi Yang*, Sandra Cvijić

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

13 Citations (Scopus)
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Abstract

This study aims to understand the absorption patterns of three different kinds of inhaled formulations via in silico modeling using budesonide (BUD) as a model drug. The formulations investigated in this study are: (i) commercially available micronized BUD mixed with lactose (BUD-PT), (ii) BUD nanocrystal suspension (BUD-NC), (iii) BUD nanocrystals embedded hyaluronic acid microparticles (BUD-NEM). The deposition patterns of the three inhaled formulations in the rats’ lungs were determined in vivo and in silico predicted, which were used as inputs in GastroPlus™ software to predict drug absorption following aerosolization of the tested formulations. BUD pharmacokinetics, estimated based on intravenous data in rats, was used to establish a drug-specific in silico absorption model. The BUD-specific in silico model revealed that drug pulmonary solubility and absorption rate constant were the key factors affecting pulmonary absorption of BUD-NC and BUD-NEM, respectively. In the case of BUD-PT, the in silico model revealed significant gastrointestinal absorption of BUD, which could be overlooked by traditional in vivo experimental observation. This study demonstrated that in vitro-in vivo-in silico approach was able to identify the key factors that influence the absorption of different inhaled formulations, which may facilitate the development of orally inhaled formulations with different drug release/absorption rates.

Original languageEnglish
JournalAsian Journal of Pharmaceutical Sciences
Volume16
Issue number3
Pages (from-to)350-362
ISSN1818-0876
DOIs
Publication statusPublished - 2021

Keywords

  • Budesonide
  • In silico physiologically-based pharmacokinetic modeling
  • Nanocrystal suspension
  • Nanocrystal-embedded microparticles
  • Pulmonary drug delivery

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