Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy

We previously reported that the bioavailability (BA) of irbesartan (IRB), a BSC class II drug, was improved by preparing nanocrystalline suspensions. However, nanocrystalline suspensions have chemical and physical instabilities and must be converted into tablets through drying approaches in order to...

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Autores principales: Nagai, Noriaki, Ogata, Fumihiko, Ike, Ayari, Shimomae, Yurisa, Osako, Hanano, Nakazawa, Yosuke, Yamamoto, Naoki, Kawasaki, Naohito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875686/
https://www.ncbi.nlm.nih.gov/pubmed/35214118
http://dx.doi.org/10.3390/pharmaceutics14020387
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author Nagai, Noriaki
Ogata, Fumihiko
Ike, Ayari
Shimomae, Yurisa
Osako, Hanano
Nakazawa, Yosuke
Yamamoto, Naoki
Kawasaki, Naohito
author_facet Nagai, Noriaki
Ogata, Fumihiko
Ike, Ayari
Shimomae, Yurisa
Osako, Hanano
Nakazawa, Yosuke
Yamamoto, Naoki
Kawasaki, Naohito
author_sort Nagai, Noriaki
collection PubMed
description We previously reported that the bioavailability (BA) of irbesartan (IRB), a BSC class II drug, was improved by preparing nanocrystalline suspensions. However, nanocrystalline suspensions have chemical and physical instabilities and must be converted into tablets through drying approaches in order to overcome such instabilities. In this study, we attempted to design a molded tablet based on nanocrystalline IRB suspensions (IRB-NP tablet) and investigated the effects of this IRB-NP tablet on blood pressure (BP) in a stroke-prone spontaneously hypertensive (SHR-SP) rat. The IRB-NP tablet (with a hardness of 42.6 N) was developed by combining various additives (methylcellulose, 2-hydroxypropyl-β-cyclodextrin HPβCD, D-mannitol, polyvinylpyrrolidone, and gum arabic) followed by bead-milling and freeze-drying treatments. The mean particle size in the redispersions of the IRB-NP tablet was approximately 118 nm. The solubility and intestinal absorption of IRB in the IRB-NP tablet were significantly enhanced in comparison with the microcrystalline IRB tablet (IRB-MP tablet), and both solubility and clathrin-dependent endocytosis helped improve the low BA of the IRB. In addition, the BP-reducing effect of the IRB-NP tablet was significantly higher than that of the IRB-MP tablet. These results provide useful information for the preservation of nanocrystalline suspensions of BCS class II drugs, such as IRB.
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spelling pubmed-88756862022-02-26 Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy Nagai, Noriaki Ogata, Fumihiko Ike, Ayari Shimomae, Yurisa Osako, Hanano Nakazawa, Yosuke Yamamoto, Naoki Kawasaki, Naohito Pharmaceutics Article We previously reported that the bioavailability (BA) of irbesartan (IRB), a BSC class II drug, was improved by preparing nanocrystalline suspensions. However, nanocrystalline suspensions have chemical and physical instabilities and must be converted into tablets through drying approaches in order to overcome such instabilities. In this study, we attempted to design a molded tablet based on nanocrystalline IRB suspensions (IRB-NP tablet) and investigated the effects of this IRB-NP tablet on blood pressure (BP) in a stroke-prone spontaneously hypertensive (SHR-SP) rat. The IRB-NP tablet (with a hardness of 42.6 N) was developed by combining various additives (methylcellulose, 2-hydroxypropyl-β-cyclodextrin HPβCD, D-mannitol, polyvinylpyrrolidone, and gum arabic) followed by bead-milling and freeze-drying treatments. The mean particle size in the redispersions of the IRB-NP tablet was approximately 118 nm. The solubility and intestinal absorption of IRB in the IRB-NP tablet were significantly enhanced in comparison with the microcrystalline IRB tablet (IRB-MP tablet), and both solubility and clathrin-dependent endocytosis helped improve the low BA of the IRB. In addition, the BP-reducing effect of the IRB-NP tablet was significantly higher than that of the IRB-MP tablet. These results provide useful information for the preservation of nanocrystalline suspensions of BCS class II drugs, such as IRB. MDPI 2022-02-10 /pmc/articles/PMC8875686/ /pubmed/35214118 http://dx.doi.org/10.3390/pharmaceutics14020387 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nagai, Noriaki
Ogata, Fumihiko
Ike, Ayari
Shimomae, Yurisa
Osako, Hanano
Nakazawa, Yosuke
Yamamoto, Naoki
Kawasaki, Naohito
Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy
title Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy
title_full Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy
title_fullStr Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy
title_full_unstemmed Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy
title_short Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy
title_sort oral formulation based on irbesartan nanocrystals improve drug solubility, absorbability, and efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875686/
https://www.ncbi.nlm.nih.gov/pubmed/35214118
http://dx.doi.org/10.3390/pharmaceutics14020387
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