In vivo pharmacokinetic and pharmacodynamic study of inhalable pirfenidone microparticles prepared via high-energy bead milling
Purpose Pirfenidone (PRF) is the first FDA-approved active pharmaceutical ingredient for the treatment of idiopathic pulmonary fibrosis (IPF). However, it has severe adverse effects such as photophobia and gastrointestinal disorder. Administration of PRF through the pulmonary route requires a relatively low effective dose and has few adverse effects. We evaluated the efficacy of inhalable PRF microparticles, which we manufactured via wet bead milling, to examine their bioavailability and efficacy when delivered through the pulmonary route as dry powder inhaler. Methods Bead milled microparticles of PRF were prepared using high-energy dry or wet bead milling. Bioavailability of PRF was confirmed via in vivo pharmacokinetic (PK) experiments; in vivo pharmacodynamic experiments were performed using a bleomycin induced IPF rat model. Results Wet bead milling was more efficient than dry bead milling owing to the high crystallinity and cohesiveness of PRF. Furthermore, in vivo PK experiments demonstrated that administering PRF via the pulmonary route was more than twice as effective as the oral route. Similarly, the therapeutic impact of PRF delivered via the pulmonary route was more optimized than that of PRF delivered via the oral route. Conclusion These findings indicate that the bioavailability, distribution in the lungs, and therapeutic effect of PRF are superior when administered via the pulmonary route compared to the oral route..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Journal of pharmaceutical investigation - 53(2023), 6 vom: Nov., Seite 869-879 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kang, Ji-Hyun [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Bead mill |
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| Anmerkungen: |
© The Author(s) under exclusive licence to The Korean Society of Pharmaceutical Sciences and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s40005-023-00640-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR053899741 |
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| 100 | 1 | |a Kang, Ji-Hyun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a In vivo pharmacokinetic and pharmacodynamic study of inhalable pirfenidone microparticles prepared via high-energy bead milling |
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| 520 | |a Purpose Pirfenidone (PRF) is the first FDA-approved active pharmaceutical ingredient for the treatment of idiopathic pulmonary fibrosis (IPF). However, it has severe adverse effects such as photophobia and gastrointestinal disorder. Administration of PRF through the pulmonary route requires a relatively low effective dose and has few adverse effects. We evaluated the efficacy of inhalable PRF microparticles, which we manufactured via wet bead milling, to examine their bioavailability and efficacy when delivered through the pulmonary route as dry powder inhaler. Methods Bead milled microparticles of PRF were prepared using high-energy dry or wet bead milling. Bioavailability of PRF was confirmed via in vivo pharmacokinetic (PK) experiments; in vivo pharmacodynamic experiments were performed using a bleomycin induced IPF rat model. Results Wet bead milling was more efficient than dry bead milling owing to the high crystallinity and cohesiveness of PRF. Furthermore, in vivo PK experiments demonstrated that administering PRF via the pulmonary route was more than twice as effective as the oral route. Similarly, the therapeutic impact of PRF delivered via the pulmonary route was more optimized than that of PRF delivered via the oral route. Conclusion These findings indicate that the bioavailability, distribution in the lungs, and therapeutic effect of PRF are superior when administered via the pulmonary route compared to the oral route. | ||
| 650 | 4 | |a Idiopathic pulmonary fibrosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Dry power inhaler |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Bead mill |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Bleomycin-induced idiopathic pulmonary fibrosis model |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Choi, Jae‑Cheol |4 aut | |
| 700 | 1 | |a Song, Woo Yul |4 aut | |
| 700 | 1 | |a Choi, Jihoon |4 aut | |
| 700 | 1 | |a Lee, Sung-Hoon |4 aut | |
| 700 | 1 | |a Park, Chun-Woong |0 (orcid)0000-0001-5329-8443 |4 aut | |
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