A novel levodopa-carbidopa three-layer gastroretentive tablet for improving levodopa pharmacokinetics

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2025-02-01 DOI:10.1016/j.ejpb.2025.114633

Xiangcheng Zhao , Peng Yan , Hailong Zhang , Wenhu Zhou , Jinsong Ding

{"title":"A novel levodopa-carbidopa three-layer gastroretentive tablet for improving levodopa pharmacokinetics","authors":"Xiangcheng Zhao , Peng Yan , Hailong Zhang , Wenhu Zhou , Jinsong Ding","doi":"10.1016/j.ejpb.2025.114633","DOIUrl":null,"url":null,"abstract":"<div><div>The narrow absorption window of levodopa and the significant impact of peripheral decarboxylase are the most limiting factors in maintaining prolonged and smooth plasma concentration in patients with Parkinson’s disease (PD). Therefore, this study aims to design a novel gastroretentive carbidopa-levodopa three-layer tablet, which consists of an expansion layer, an immediate-release layer, and a sustained-release layer. The expansion layer rapidly expanded with sufficient structural strength and stayed in the beagle’s stomach for more than 10 h, delineating excellent gastric retention effects. The immediate-release layer quickly released the drug and the sustained-release layer maintained a stable drug concentration. Importantly, pharmacokinetic data obtained under fed conditions demonstrated that the duration of efficacy of the three-layer tablets was significantly superior to that of the commercially available product Sinemet® CR, with effective levodopa blood levels remaining for up to 12 h. This is expected to offer more convenient clinical medication options for patients with PD.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"207 ","pages":"Article 114633"},"PeriodicalIF":4.4000,"publicationDate":"2025-02-01","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/S0939641125000098","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

The narrow absorption window of levodopa and the significant impact of peripheral decarboxylase are the most limiting factors in maintaining prolonged and smooth plasma concentration in patients with Parkinson’s disease (PD). Therefore, this study aims to design a novel gastroretentive carbidopa-levodopa three-layer tablet, which consists of an expansion layer, an immediate-release layer, and a sustained-release layer. The expansion layer rapidly expanded with sufficient structural strength and stayed in the beagle’s stomach for more than 10 h, delineating excellent gastric retention effects. The immediate-release layer quickly released the drug and the sustained-release layer maintained a stable drug concentration. Importantly, pharmacokinetic data obtained under fed conditions demonstrated that the duration of efficacy of the three-layer tablets was significantly superior to that of the commercially available product Sinemet® CR, with effective levodopa blood levels remaining for up to 12 h. This is expected to offer more convenient clinical medication options for patients with PD.

Abstract Image

查看原文本刊更多论文

一种改善左旋多巴药代动力学的新型左旋多巴卡比多巴三层胃保留片。

左旋多巴的狭窄吸收窗口和外周脱羧酶的显著影响是帕金森病患者维持长时间平稳血药浓度的最大限制因素。因此，本研究旨在设计一种新型胃保性卡比多巴-左旋多巴三层片剂，该片剂由膨胀层、速释层和缓释层组成。膨胀层迅速膨胀，结构强度充足，在小猎犬胃内停留时间超过10 h，胃潴留效果极佳。速释层快速释放药物，缓释层维持稳定的药物浓度。重要的是，在饲喂条件下获得的药代动力学数据表明，三层片的药效持续时间明显优于市售产品Sinemet®CR，有效左旋多巴血药浓度可维持12 h。这有望为帕金森病患者提供更方便的临床用药选择。

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分钟内获得全文求助全文

来源期刊

European Journal of Pharmaceutics and Biopharmaceutics 医学-药学

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.