Improving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation
Hongfei Liu,1 Jiaao Mei,1 Ying Xu,1 Lei Tang,1 Daquan Chen,2 Yating Zhu,1 Shuguang Huang,1 Thomas J Webster,3 Hui Ding4 1College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2School of Pharmacy, Yantai University, Yantai 264005, People’s Republic...
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Dove Medical Press
2019
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oai:doaj.org-article:0f8b7c1c65c9461c81685d7d79d9d6122021-12-02T06:56:50ZImproving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation1178-2013https://doaj.org/article/0f8b7c1c65c9461c81685d7d79d9d6122019-11-01T00:00:00Zhttps://www.dovepress.com/improving-the-oral-absorption-of-nintedanib-by-a-self-microemulsion-dr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hongfei Liu,1 Jiaao Mei,1 Ying Xu,1 Lei Tang,1 Daquan Chen,2 Yating Zhu,1 Shuguang Huang,1 Thomas J Webster,3 Hui Ding4 1College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2School of Pharmacy, Yantai University, Yantai 264005, People’s Republic of China; 3Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 4Department of Respiratory and Critical Care Medicine, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, People’s Republic of ChinaCorrespondence: Hui DingDepartment of Respiratory and Critical Care Medicine, The Affiliated Yixing Hospital Of Jiangsu University, Yixing, Jiangsu 214200, People’s Republic of ChinaTel +8601370656506Email dh1350519@163.comThomas J WebsterDepartment Of Chemical Engineering, Northeastern University, Boston, MA 02115, USA, Tel +1 617 373 6585Email th.webster@neu.eduObjective: Nintedanib (NDNB) is a triple receptor tyrosine kinase inhibitor with poor solubility in neutral conditions and low bioavailability. A self-microemulsifying drug delivery system (SMEDDS) of NDNB was developed to improve drug solubility in physical conditions and absorption in vivo.Methods: The NDNB-SMEDDS formulation was optimized via pseudo-ternary phase diagrams. The physicochemical properties of NDNB-SMEDDS, viz., morphological observation, droplet size, stability, compatibility and in vitro release were investigated. The permeability of NDNB-SMEDDS was detected using both a Caco-2 cell monolayer in vitro and an intestinal perfusion study in vivo. Furthermore, the pharmacokinetic characteristics of NDNB-SMEDDS were evaluated.Results: The optimal formulation was composed of MCT as an oil phase, RH 40 as a surfactant and ethylene glycol as a co-surfactant. The average droplet size of the microemulsion was about 23 nm with good stability within 30 days. The formulation did not exhibit any obvious cytotoxic effect on Caco-2 cells. Permeability of nintedanib in a Caco-2 cell monolayer was enhanced by 2.8-fold upon incorporation in SMEDDS compared with the drug solution. The intestinal perfusion study demonstrated that the Papp of NDNB-SMEDDS increased by 3.0-fold in the entire intestine and 3.2-fold in the colon in comparison with the drug solution. The pharmacokinetics study showed that the AUC of the NDNB-SMEDDS increased significantly.Conclusion: This study showed that the self-microemulsion formulations could improve the absorption of nintedanib, and can thus serve as a promising carrier for the oral delivery of nintedanib.Keywords: nintedanib, self-microemulsion drug delivery system, solubility, permeability, Caco-2 cell, intestinal perfusion, pharmacokinetics, bioavailabilityLiu HMei JXu YTang LChen DZhu YHuang SWebster TJDing HDove Medical Pressarticlenintedanibself-microemulsion drug delivery systemsolubilitypermeabilitycaco-2 cellintestinal perfusionpharmacokineticsbioavailability.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8739-8751 (2019) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
nintedanib self-microemulsion drug delivery system solubility permeability caco-2 cell intestinal perfusion pharmacokinetics bioavailability. Medicine (General) R5-920 |
| spellingShingle |
nintedanib self-microemulsion drug delivery system solubility permeability caco-2 cell intestinal perfusion pharmacokinetics bioavailability. Medicine (General) R5-920 Liu H Mei J Xu Y Tang L Chen D Zhu Y Huang S Webster TJ Ding H Improving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation |
| description |
Hongfei Liu,1 Jiaao Mei,1 Ying Xu,1 Lei Tang,1 Daquan Chen,2 Yating Zhu,1 Shuguang Huang,1 Thomas J Webster,3 Hui Ding4 1College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2School of Pharmacy, Yantai University, Yantai 264005, People’s Republic of China; 3Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 4Department of Respiratory and Critical Care Medicine, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu 214200, People’s Republic of ChinaCorrespondence: Hui DingDepartment of Respiratory and Critical Care Medicine, The Affiliated Yixing Hospital Of Jiangsu University, Yixing, Jiangsu 214200, People’s Republic of ChinaTel +8601370656506Email dh1350519@163.comThomas J WebsterDepartment Of Chemical Engineering, Northeastern University, Boston, MA 02115, USA, Tel +1 617 373 6585Email th.webster@neu.eduObjective: Nintedanib (NDNB) is a triple receptor tyrosine kinase inhibitor with poor solubility in neutral conditions and low bioavailability. A self-microemulsifying drug delivery system (SMEDDS) of NDNB was developed to improve drug solubility in physical conditions and absorption in vivo.Methods: The NDNB-SMEDDS formulation was optimized via pseudo-ternary phase diagrams. The physicochemical properties of NDNB-SMEDDS, viz., morphological observation, droplet size, stability, compatibility and in vitro release were investigated. The permeability of NDNB-SMEDDS was detected using both a Caco-2 cell monolayer in vitro and an intestinal perfusion study in vivo. Furthermore, the pharmacokinetic characteristics of NDNB-SMEDDS were evaluated.Results: The optimal formulation was composed of MCT as an oil phase, RH 40 as a surfactant and ethylene glycol as a co-surfactant. The average droplet size of the microemulsion was about 23 nm with good stability within 30 days. The formulation did not exhibit any obvious cytotoxic effect on Caco-2 cells. Permeability of nintedanib in a Caco-2 cell monolayer was enhanced by 2.8-fold upon incorporation in SMEDDS compared with the drug solution. The intestinal perfusion study demonstrated that the Papp of NDNB-SMEDDS increased by 3.0-fold in the entire intestine and 3.2-fold in the colon in comparison with the drug solution. The pharmacokinetics study showed that the AUC of the NDNB-SMEDDS increased significantly.Conclusion: This study showed that the self-microemulsion formulations could improve the absorption of nintedanib, and can thus serve as a promising carrier for the oral delivery of nintedanib.Keywords: nintedanib, self-microemulsion drug delivery system, solubility, permeability, Caco-2 cell, intestinal perfusion, pharmacokinetics, bioavailability |
| format |
article |
| author |
Liu H Mei J Xu Y Tang L Chen D Zhu Y Huang S Webster TJ Ding H |
| author_facet |
Liu H Mei J Xu Y Tang L Chen D Zhu Y Huang S Webster TJ Ding H |
| author_sort |
Liu H |
| title |
Improving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation |
| title_short |
Improving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation |
| title_full |
Improving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation |
| title_fullStr |
Improving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation |
| title_full_unstemmed |
Improving The Oral Absorption Of Nintedanib By A Self-Microemulsion Drug Delivery System: Preparation And In Vitro/In Vivo Evaluation |
| title_sort |
improving the oral absorption of nintedanib by a self-microemulsion drug delivery system: preparation and in vitro/in vivo evaluation |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/0f8b7c1c65c9461c81685d7d79d9d612 |
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