Fabrication of Electrospun Levodopa-Carbidopa Fixed-Dose Combinations

Haitham Bukhary,Mine Orlu,Gareth R Williams

doi:10.1007/s42765-020-00031-1

Haitham Bukhary, Mine Orlu + Show 1 more

Open Access

https://doi.org/10.1007/s42765-020-00031-1

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Abstract

We report in this work coaxial electrospun fibers with potential applications in the treatment of Parkinson’s disease. The fibers comprise a fixed dose combination (FDC) containing the active ingredients levodopa and carbidopa, loaded in a fast dissolving polyvinylpyrrolidone (PVP) shell and an insoluble but swellable Eudragit® RLPO core. Under appropriate processing conditions we are able to prepare fibers with distinct core/shell architectures and diameters of approximately 400 nm. X-ray diffraction and differential scanning calorimetry analyses revealed that the drugs are dispersed on the molecular level within the polymer carriers, and IR spectroscopy indicated the presence of intermolecular interactions. At pH 1, the composite fibers yields extended release over more than 8 h, with an initial loading dose being freed from the PVP shell and then a sustained release phase following from the insoluble core. This is markedly extended over the release period of the commercial FDC product, and thus the fibers generated here have the potential to be used to reduce the required dosing frequency.Graphic

Highlights

Parkinson’s disease (PD) is a disabling disorder that significantly affects a patient’s quality of life [1]
Two model drugs (LD and CD) were loaded, resulting in an FDC which could be used for the treatment of PD
Scanning electron microscopy (SEM) images showed the production of cylindrical fibers with smooth surfaces

Summary

Introduction

Parkinson’s disease (PD) is a disabling disorder that significantly affects a patient’s quality of life [1]. Treatments are available, but only 10% of PD patients fully adhere to their treatment regimens [2]. Non-adherence is a serious problem linked to worsening symptoms and increased motor fluctuations [3,4,5]. Levodopa (LD) remains the most effective treatment for PD [6]. A single dosing treatment is only effective in the early phase of the disease. 4–5 years after diagnosis, the therapeutic window of dopamine becomes narrow, and due to its short half-life of between 0.7 and 1.4 h dosing of LD will be required every 2 h [7,8,9]. One way to ameliorate this issue is to co-administer LD with carbidopa (CD), which can increase LD’s oral bioavailability to 40–70% [10]

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