{"title":"Binary and Ternary Inclusion Complexes of Niflumic Acid: Synthesis, Characterization, and Dissolution Profile","authors":"Zohra Bouchekhou, Amel Hadj Ziane-Zafour, Florentina Geanina Lupascu, Bianca-Ștefania Profire, Alina Nicolescu, Denisse-Iulia Bostiog, Florica Doroftei, Ioan-Andrei Dascalu, Cristian-Dragoș Varganici, Mariana Pinteala, Lenuta Profire, Tudor Pinteala, Bachir Bouzid","doi":"10.3390/pharmaceutics16091190","DOIUrl":null,"url":null,"abstract":"Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug–cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects.","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/pharmaceutics16091190","RegionNum":3,"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
Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug–cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects.
尽管硝氟酸(NA)是最常用的非甾体抗炎药物之一,但它的溶解性差、生物利用度低、不良反应大。为了解决这些局限性,NA 与环糊精(CD)的复配是一种很有前景的策略。然而,将 CD 与 NA 等低分子量药物络合会导致低 CE。本研究探讨了NA与2-羟丙基-β-环糊精(2HP-β-CD)包合复合物的开发,包括将NA转化为其钠盐(NAs)和添加羟丙基甲基纤维素(HPMC)对复合物形成的影响。利用共蒸发溶剂法和冷冻干燥法制备了包合物,并通过相溶解度研究确定了它们的CE和Ks。利用傅立叶变换红外光谱(FT-IR)、扫描电镜(DSC)、电子显微镜(SEM)、X 射线衍射(XRD)、激光光散射(DLS)、紫外可见光谱(UV-Vis)、1H-核磁共振(1H-NMR)和 1H-ROESY 等理化分析对复合物进行了表征。此外,还对复合物的溶解曲线进行了评估。分析结果表明,所有体系都形成了复合物,显示出药物与环糊精之间的相互作用、无定形药物状态、形态变化以及溶解度和溶解曲线的改善。NAs-2HP-β-CD-HPMC 复合物的 CE 值和 Ks 值最高,主客体摩尔比为 1:1,溶解情况最好。结果表明,NAs-2HP-β-CD-HPMC 复合物具有递送 NA 的潜力,可提高 NA 的疗效并减少副作用。
PharmaceuticsPharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.90
自引率
11.10%
发文量
2379
审稿时长
16.41 days
期刊介绍:
Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.