Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-09-14 DOI:10.1016/j.ijpx.2024.100284
{"title":"Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model","authors":"","doi":"10.1016/j.ijpx.2024.100284","DOIUrl":null,"url":null,"abstract":"<div><p>Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t<sub>1/2</sub> problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, <em>in vitro</em> release, release kinetics mathematical modeling, and an <em>in vivo</em> pain model in dogs undergoing orthopedic surgeries, followed by <em>in vivo</em> pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved <em>in vitro</em> controlled release pattern and an enhanced <em>in vivo</em> pharmacokinetic behavior as manifested by higher t<sub>1/2</sub> and AUC<sub>0</sub><sub>–</sub><sub>24</sub> and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156724000562/pdfft?md5=eceec16a3d26a2520d27669657dd08b7&pid=1-s2.0-S2590156724000562-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics: X","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590156724000562","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

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC024 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

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
开发新型肌肉注射脂质体,用于美洛昔康的高级给药:骨科疼痛模型的制备、表征、体内药代动力学、药效学和疼痛评估
疼痛会产生多种生理和退行性并发症。本研究旨在将美洛昔康(MLX)配制成脂质体,以增加其溶解度,并以可控方式递送 MLX,从而克服其水溶性差和 t1/2 较短的问题。脂质体的制备方法是薄膜水合,然后进行超声处理。表征制剂特性的测试包括粒度、跨度、夹持效率、载药量、稳定性、差示扫描量热法(DSC)、傅立叶变换红外光谱法(FT-IR)、形态学、体外释放、释放动力学数学建模,以及在接受骨科手术的狗身上进行的体内疼痛模型试验,随后进行了体内药代动力学、药效学和疼痛评估研究,并与参考标准 Mobitil® 进行了比较。脂质体 MLX 的粒径约为 100 纳米,包埋效率为 82%,药物负载率为 4.62%。稳定性研究、DSC 和傅立叶变换红外光谱显示,脂质体具有很高的稳定性。与 Mobitil® 相比,该制剂的体外控释模式得到了改善,体内药代动力学行为也得到了增强,表现为更高的 t1/2、AUC0-24 和更低的 Cl/F。药效学研究和疼痛量表显示,脂质体 MLX 比 Mobitil® 能更好地控制术后疼痛。总之,在脂质体中加入 MLX 可提高其溶解度和稳定性,以及镇痛特性。
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
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
期刊最新文献
From design to 3D printing: A proof-of-concept study for multiple unit particle systems (MUPS) printed by dual extrusion fused filament fabrication Augmented glycerosomes as a promising approach against fungal ear infection: Optimization and microbiological, ex vivo and in vivo assessments Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8-O-methylfusarubin for breast cancer treatment Effect of wound dressing porosity and exudate viscosity on the exudate absorption: In vitro and in silico tests with 3D printed hydrogels
×
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