Preparation, Characterization and Evaluation of Nintedanib Amorphous Solid Dispersions with Enhanced Oral Bioavailability

doi:10.1208/s12249-024-02902-x

科研成果详情

题名	Preparation, Characterization and Evaluation of Nintedanib Amorphous Solid Dispersions with Enhanced Oral Bioavailability
作者	Liu, Shuyin1,2; Chen, Hui 2; Zhou, Feng 2; Tiwari, Sandip 3; Zhuang, Kai 4; Shan, Yudong 5; Zhang, Jiantao 1,2
发表日期	2024-08-13
发表期刊	AAPS PHARMSCITECH 影响因子和分区
语种	英语
原始文献类型	Article
关键词	amorphous solid dispersion hot melt extrusion nintedanib oral bioavailability
其他关键词	HOT-MELT EXTRUSION ; PHYSICAL STABILITY ; DELIVERY SYSTEM ; DRUG ; DISSOLUTION ; SOLUBILITY ; PERMEABILITY ; TELMISARTAN ; ABSORPTION ; CHALLENGES
摘要	The dissolution and bioavailability challenges posed by poorly water-soluble drugs continue to drive innovation in pharmaceutical formulation design. Nintedanib (NDNB) is a typical BCS class II drug that has been utilized to treat idiopathic pulmonary fibrosis (IPF). Due to the low solubility, its oral bioavailability is relatively low, limiting its therapeutical effectiveness. It is crucial to enhance the dissolution and the oral bioavailability of NDNB. In this study, we focused on the preparation of amorphous solid dispersions (ASD) using hot melt extrusion (HME). The formulation employed Kollidon (R) VA64 (VA64) as the polymer matrix, blended with the NDNB at a ratio of 9:1. HME was conducted at temperatures ranging from 80 degrees C to 220 degrees C. The successful preparation of ASD was confirmed through various tests including polarized light microscopy (PLM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). The in-vitro cumulative release of NDNB-ASD in 2 h in a pH 6.8 medium was 8.3-fold higher than that of NDNB (p < 0.0001). In a pH 7.4 medium, it was 10 times higher (p < 0.0001). In the in-vivo pharmacokinetic experiments, the area under curve (AUC) of NDNB-ASD was 5.3-fold higher than that of NDNB and 2.2 times higher than that of commercially available soft capsules (Ofev (R)) (p < 0.0001). There was no recrystallization after 6 months under accelarated storage test. Our study indicated that NDNB-ASD can enhance the absorption of NDNB, thus providing a promising method to improve NDNB bioavailability in oral dosages.
资助项目	Natural Science Foundation of Zhejiang Province [HDMZ23H300005]
出版者	SPRINGER
ISSN	1530-9932
卷号	25 期号:6
DOI	10.1208/s12249-024-02902-x
页数	13
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001291148700004
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39138765
SCOPUSEID	2-s2.0-85201246925
通讯作者地址	[Zhang, Jiantao]Wenzhou Med Univ, Cixi Biomed Res Inst, Cixi 315300, Peoples R China. ; [Zhang, Jiantao]Chinese Acad Sci, Ningbo Inst Mat Technol & Engn, Lab Adv Theranost Mat & Technol, Ningbo 315201, Peoples R China.
Scopus学科分类	Pharmaceutical Science
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/217367
专题	其他_温州医科大学慈溪生物医药研究院
通讯作者	Zhang, Jiantao
作者单位	1.Wenzhou Med Univ, Cixi Biomed Res Inst, Cixi 315300, Peoples R China; 2.Chinese Acad Sci, Ningbo Inst Mat Technol & Engn, Lab Adv Theranost Mat & Technol, Ningbo 315201, Peoples R China; 3.BASF Corp, Pharma Solut, 500 White Plains Rd, Tarrytown, NY 10591 USA; 4.BASF China Co Ltd, Pharm Solut Nutr & Hlth, 333 Jiang Xin Sha Rd, Shanghai 200137, Peoples R China; 5.Hangzhou Zhongmeihuadong Pharmaceut Co Ltd, 866 Moganshan Rd, Hangzhou 310011, Peoples R China
第一作者单位	其他_温州医科大学慈溪生物医药研究院
通讯作者单位	其他_温州医科大学慈溪生物医药研究院
第一作者的第一单位	其他_温州医科大学慈溪生物医药研究院
推荐引用方式 GB/T 7714	Liu, Shuyin,Chen, Hui,Zhou, Feng,et al. Preparation, Characterization and Evaluation of Nintedanib Amorphous Solid Dispersions with Enhanced Oral Bioavailability[J]. AAPS PHARMSCITECH,2024,25(6).
APA	Liu, Shuyin., Chen, Hui., Zhou, Feng., Tiwari, Sandip., Zhuang, Kai., ... & Zhang, Jiantao. (2024). Preparation, Characterization and Evaluation of Nintedanib Amorphous Solid Dispersions with Enhanced Oral Bioavailability. AAPS PHARMSCITECH, 25(6).
MLA	Liu, Shuyin,et al."Preparation, Characterization and Evaluation of Nintedanib Amorphous Solid Dispersions with Enhanced Oral Bioavailability".AAPS PHARMSCITECH 25.6(2024).