In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug
Authors
Shi, ChangzhiIgnjatović, Jelisaveta
Liu, Tingting
Han, Meihua
Cun, Dongmei
Đuriš, Jelena
Yang, Mingshi
Cvijić, Sandra
Article (Published version)
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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.
Keywords:
Budesonide / In silico physiologically-based pharmacokinetic modeling / Nanocrystal suspension / Nanocrystal-embedded microparticles / Pulmonary drug deliverySource:
Asian Journal of Pharmaceutical Sciences, 2021, 16, 3, 350-362Publisher:
- Elsevier B.V.
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200161 (University of Belgrade, Faculty of Pharmacy) (RS-MESTD-inst-2020-200161)
- National Natural Science Foundation of China (Nos.81302720 and No.81573380)
- European Cooperation in Science and Technology
DOI: 10.1016/j.ajps.2020.12.001
ISSN: 1818-0876
WoS: 000669676300008
Scopus: 2-s2.0-85102878238
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Institution/Community
PharmacyTY - JOUR AU - Shi, Changzhi AU - Ignjatović, Jelisaveta AU - Liu, Tingting AU - Han, Meihua AU - Cun, Dongmei AU - Đuriš, Jelena AU - Yang, Mingshi AU - Cvijić, Sandra PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3902 AB - 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. PB - Elsevier B.V. T2 - Asian Journal of Pharmaceutical Sciences T1 - In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug VL - 16 IS - 3 SP - 350 EP - 362 DO - 10.1016/j.ajps.2020.12.001 ER -
@article{ author = "Shi, Changzhi and Ignjatović, Jelisaveta and Liu, Tingting and Han, Meihua and Cun, Dongmei and Đuriš, Jelena and Yang, Mingshi and Cvijić, Sandra", year = "2021", 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.", publisher = "Elsevier B.V.", journal = "Asian Journal of Pharmaceutical Sciences", title = "In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug", volume = "16", number = "3", pages = "350-362", doi = "10.1016/j.ajps.2020.12.001" }
Shi, C., Ignjatović, J., Liu, T., Han, M., Cun, D., Đuriš, J., Yang, M.,& Cvijić, S.. (2021). In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug. in Asian Journal of Pharmaceutical Sciences Elsevier B.V.., 16(3), 350-362. https://doi.org/10.1016/j.ajps.2020.12.001
Shi C, Ignjatović J, Liu T, Han M, Cun D, Đuriš J, Yang M, Cvijić S. In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug. in Asian Journal of Pharmaceutical Sciences. 2021;16(3):350-362. doi:10.1016/j.ajps.2020.12.001 .
Shi, Changzhi, Ignjatović, Jelisaveta, Liu, Tingting, Han, Meihua, Cun, Dongmei, Đuriš, Jelena, Yang, Mingshi, Cvijić, Sandra, "In vitro - in vivo - in silico approach in the development of inhaled drug products: Nanocrystal-based formulations with budesonide as a model drug" in Asian Journal of Pharmaceutical Sciences, 16, no. 3 (2021):350-362, https://doi.org/10.1016/j.ajps.2020.12.001 . .