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.
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