Design and development of Fujicalin-based axitinib liquisolid compacts for improved dissolution and bioavailability to treat renal cell carcinoma

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-09-19 DOI:10.1016/j.ejpb.2024.114506
Priyanka S. Yadav , Ashok A. Hajare , Kiran S. Patil
{"title":"Design and development of Fujicalin-based axitinib liquisolid compacts for improved dissolution and bioavailability to treat renal cell carcinoma","authors":"Priyanka S. Yadav ,&nbsp;Ashok A. Hajare ,&nbsp;Kiran S. Patil","doi":"10.1016/j.ejpb.2024.114506","DOIUrl":null,"url":null,"abstract":"<div><div>Poor dissolution of axitinib (AXT) limits its effectiveness through the oral route. The present study investigated, prospective of liquisolid (LS) technology to improve dissolution rate and oral bioavailability of AXT to treat renal cell carcinoma. LS compacts were fabricated with PEG 200, Fujicalin SG, and Aerosil 200 as solvent, carrier, and coat material, respectively. The behavior of LS-systems during tabletting was investigated using Kawakita, Heckel, and Leuenberger analysis. LS compacts were examined for <em>P</em>-XRD, DSC, SEM, and <em>in vitro</em> drug dissolution. For optimization, a 3<sup>2</sup> full factorial design was utilized. Cell line A498 was utilized for <em>in vitro</em> cytotoxicity study. A bioavailability study was performed using rabbits. DSC and <em>P</em>-XRD analysis confirmed the transition of crystalline AXT to its partial amorphization and molecular dispersion. Consequently, LS6 demonstrated a significantly rapid drug dissolution (Q<sub>20</sub>; &gt;99 %) than the directly compressed tablets (18.05 %). Additionally, 2.03-fold increase in oral bioavailability, and inhibited dose-dependent cell growth with 1.75-fold increased apoptosis rate. Overall, an LS6 compact consisting of 15 % AXT concentration in PEG 200 and a 20 w/w ratio of Fujicalin SG: Aerosil 200 exhibited improved formulation properties, enhanced dissolution rate, and bioavailability. Thus developed potential product may contribute low-cost production with patient-improved survival expectations.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"204 ","pages":"Article 114506"},"PeriodicalIF":4.4000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutics and Biopharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0939641124003321","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Poor dissolution of axitinib (AXT) limits its effectiveness through the oral route. The present study investigated, prospective of liquisolid (LS) technology to improve dissolution rate and oral bioavailability of AXT to treat renal cell carcinoma. LS compacts were fabricated with PEG 200, Fujicalin SG, and Aerosil 200 as solvent, carrier, and coat material, respectively. The behavior of LS-systems during tabletting was investigated using Kawakita, Heckel, and Leuenberger analysis. LS compacts were examined for P-XRD, DSC, SEM, and in vitro drug dissolution. For optimization, a 32 full factorial design was utilized. Cell line A498 was utilized for in vitro cytotoxicity study. A bioavailability study was performed using rabbits. DSC and P-XRD analysis confirmed the transition of crystalline AXT to its partial amorphization and molecular dispersion. Consequently, LS6 demonstrated a significantly rapid drug dissolution (Q20; >99 %) than the directly compressed tablets (18.05 %). Additionally, 2.03-fold increase in oral bioavailability, and inhibited dose-dependent cell growth with 1.75-fold increased apoptosis rate. Overall, an LS6 compact consisting of 15 % AXT concentration in PEG 200 and a 20 w/w ratio of Fujicalin SG: Aerosil 200 exhibited improved formulation properties, enhanced dissolution rate, and bioavailability. Thus developed potential product may contribute low-cost production with patient-improved survival expectations.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
设计和开发基于藤黄素的阿西替尼利尿固化物,提高其溶解度和生物利用度,以治疗肾细胞癌。
阿西替尼(AXT)的溶解度较低,限制了其通过口服途径的有效性。本研究探讨了利用Liquisolid(LS)技术提高阿西替尼溶解率和口服生物利用度以治疗肾细胞癌的前景。研究人员分别以 PEG 200、Fujicalin SG 和 Aerosil 200 作为溶剂、载体和包衣材料,制成了液相固体。使用 Kawakita、Heckel 和 Leuenberger 分析法研究了 LS 系统在压片过程中的行为。此外,还对 LS 紧凑型产品进行了 P-XRD、DSC、SEM 和体外药物溶解度检测。在优化方面,采用了 32 全因子设计。体外细胞毒性研究采用了 A498 细胞系。利用兔子进行了生物利用度研究。DSC 和 P-XRD 分析证实了 AXT 结晶向部分非晶化和分子分散的转变。因此,与直接压片(18.05%)相比,LS6 的药物溶出速度(Q20;>99%)明显更快。此外,LS6 的口服生物利用度提高了 2.03 倍,并能抑制剂量依赖性细胞生长,使细胞凋亡率提高了 1.75 倍。总之,由 15 % AXT 浓度的 PEG 200 和 20 w/w 比率的藤黄素 SG: Aerosil 200 组成的 LS6 密实剂具有更好的制剂特性、更高的溶出率和生物利用率。因此,所开发的潜在产品可实现低成本生产,并提高患者的存活率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
期刊最新文献
A multifaceted approach to understanding protein-buffer interactions in biopharmaceuticals Continuous twin-screw melt granulation of drug-loaded electrospun fibers Homogeneity analysis of medicine tablets by laser induced breakdown spectroscopy combined with multivariate methods Antifungal peptide-loaded alginate microfiber wound dressing evaluated against Candida albicans in vitro and ex vivo Challenges in the development of long acting injectable multivesicular liposomes (DepoFoam® technology)
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1