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Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization
Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded soli...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704533/ https://www.ncbi.nlm.nih.gov/pubmed/34946619 http://dx.doi.org/10.3390/molecules26247538 |
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author | Dudhipala, Narendar Ettireddy, Swetha Youssef, Ahmed Adel Ali Puchchakayala, Goverdhan |
author_facet | Dudhipala, Narendar Ettireddy, Swetha Youssef, Ahmed Adel Ali Puchchakayala, Goverdhan |
author_sort | Dudhipala, Narendar |
collection | PubMed |
description | Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded solid lipid nanoparticles (IR-CD-SLNs) for enhanced solubility, sustained release behavior, and subsequently improved bioavailability through oral administration. Based on phase solubility studies, solid complexes were prepared by the coacervation followed by lyophilization method and characterized for drug content, inclusion efficiency, solubility, and in vitro dissolution. IR-CD inclusion complexes demonstrated enhancement of solubility and dissolution rate of IR. However, the dissolution efficiency was significantly increased with hydroxypropyl-βCD (HP-βCD) inclusion complex than beta-CD (βCD). SLNs were obtained by hot homogenization coupled with the ultrasonication method with IR/HP-βCD inclusion complex loaded into Dynasan 112 and glycerol monostearate (GMS). SLNs were evaluated for physicochemical characteristics, in vitro release, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and physical stability at room temperature for two months. The optimized SLNs formulation showed particle size, polydispersity index, zeta potential, assay, and entrapment efficiency of 257.6 ± 5.1 nm, 0.21 ± 0.03, −30.5 ± 4.1 mV, 99.8 ± 2.5, and 93.7 ± 2.5%, respectively. IR-CD-SLN and IR-SLN dispersions showed sustained release of IR compared to the IR-CD inclusion complexes. DSC results complimented PXRD results by the absence of IR endothermic peak. Optimized IR-CD complex, IR-SLN, and IR-CD-SLN formulations were stable for two months at room temperature. Thus, the current IR oral formulation may exhibit improved oral bioavailability and prolonged antihypertensive activity, which may improve therapeutic outcomes in the treatment of hypertension and heart failure. |
format | Online Article Text |
id | pubmed-8704533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87045332021-12-25 Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization Dudhipala, Narendar Ettireddy, Swetha Youssef, Ahmed Adel Ali Puchchakayala, Goverdhan Molecules Article Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded solid lipid nanoparticles (IR-CD-SLNs) for enhanced solubility, sustained release behavior, and subsequently improved bioavailability through oral administration. Based on phase solubility studies, solid complexes were prepared by the coacervation followed by lyophilization method and characterized for drug content, inclusion efficiency, solubility, and in vitro dissolution. IR-CD inclusion complexes demonstrated enhancement of solubility and dissolution rate of IR. However, the dissolution efficiency was significantly increased with hydroxypropyl-βCD (HP-βCD) inclusion complex than beta-CD (βCD). SLNs were obtained by hot homogenization coupled with the ultrasonication method with IR/HP-βCD inclusion complex loaded into Dynasan 112 and glycerol monostearate (GMS). SLNs were evaluated for physicochemical characteristics, in vitro release, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and physical stability at room temperature for two months. The optimized SLNs formulation showed particle size, polydispersity index, zeta potential, assay, and entrapment efficiency of 257.6 ± 5.1 nm, 0.21 ± 0.03, −30.5 ± 4.1 mV, 99.8 ± 2.5, and 93.7 ± 2.5%, respectively. IR-CD-SLN and IR-SLN dispersions showed sustained release of IR compared to the IR-CD inclusion complexes. DSC results complimented PXRD results by the absence of IR endothermic peak. Optimized IR-CD complex, IR-SLN, and IR-CD-SLN formulations were stable for two months at room temperature. Thus, the current IR oral formulation may exhibit improved oral bioavailability and prolonged antihypertensive activity, which may improve therapeutic outcomes in the treatment of hypertension and heart failure. MDPI 2021-12-13 /pmc/articles/PMC8704533/ /pubmed/34946619 http://dx.doi.org/10.3390/molecules26247538 Text en © 2021 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 Dudhipala, Narendar Ettireddy, Swetha Youssef, Ahmed Adel Ali Puchchakayala, Goverdhan Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization |
title | Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization |
title_full | Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization |
title_fullStr | Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization |
title_full_unstemmed | Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization |
title_short | Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design, Development, and In Vitro Characterization |
title_sort | cyclodextrin complexed lipid nanoparticles of irbesartan for oral applications: design, development, and in vitro characterization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704533/ https://www.ncbi.nlm.nih.gov/pubmed/34946619 http://dx.doi.org/10.3390/molecules26247538 |
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