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Development, Optimization, and Evaluation In Vitro/In Vivo of Oral Liquid System for Synchronized Sustained Release of Levodopa/Benserazide

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Abstract

To enhance efficiency, convenience, and safety of Parkinson’s disease (PD) treatment for geriatric patients, an advanced suspension of Levodopa/Benserazide hydrochloride (LD/BH) has been prepared by cation-exchange resin and used to synchronize sustained release of LD and BH by optimizing coating parameters and prescription. For the purpose, LD and BH were immobilized on the surface of cation-exchange resin, respectively. Based on HPLC results, the cation-exchange resin showed high loading capacity. The studies on drug loading mechanism indicated that both drugs were immobilized by electrostatic interaction rather than physical adsorption. After PEG modification, pretreated drug-resin complexes were coated by emulsion–solvent evaporation method. In order to control drug release in a sustained manner, coating parameters of drug-resin microcapsules were optimized respectively by single-factor analysis. Further, coating prescription of the microcapsules was optimized to synchronize sustained release of LD and BH in vitro by orthogonal design. Utilizing optimal LD-resin microcapsules and BH-resin microcapsules, LD/BH suspension, containing both of them, was prepared by an optimal formulation and characterized by accelerated test and pharmacokinetic study in vivo. The accelerated test confirmed high stability of LD/BH suspension. According to pharmacokinetic results in vivo, in contrast with LD/BH commercial tablets, LD/BH suspensions did not only synchronize sustained release of both drugs but also show good bioequivalence. As LD/BH sustained release suspension can synchronize sustained release of multiple active ingredients by oral administration, the suspension presents promising oral dosage forms for geriatric patients with PD.

An advanced Levodopa/Benserazide hydrochloride (LD/BH) suspension, prepared by cation-exchange resin and optimized microencapsulation, synchronizes sustained releases of LD and BH in vivo to benefit Parkinson’s disease treatment for geriatric patients.

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Funding

This manuscript has been sponsored by the National Natural Science Foundation of China [No. 51602656 and No. 21707053], Nature Science Foundation of Jiangsu Province [No. BK20140577 and No. BK20160546], Postdoctoral Science Foundation of Jiangsu Province [No. 2018K272C and No. 2018K057C], China Postdoctoral Science Foundation [No. 2017M610309 and 2019M651730], the Scientific Research Foundation of Jiangsu University [No. 16JDG054 and No.11JDG122], the Training Project of Jiangsu university for Young Key Teachers [No. 5521290003], Suzhou Gusu Technology Angels Project [No. CYTS2017016], the Zhenjiang key research and development plan [No. SH2017003], the Jurong City Blessed Land Excellence Program [No. 201607], and Jiangyin Industry Prospective Technology Research and Development Program [No. JY0602A010101180020PB].

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Authors and Affiliations

  1. College of Pharmacy, Jiangsu University, No.301, Xuefu Road, Zhenjiang, 212013, China

    Yang Qu, Wen-Long Lai, Yuan-Rong Xin, Yuan Zhu, Li Wang, Ying Xu & Hong-Fei Liu

  2. Chia Tai Qingjiang Pharmaceutical Industry Co., Ltd, Huaian, 223001, China

    Yang Qu

  3. Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing, 210023, China

    Fei-Qin Zhu

  4. Jiangsu Sihuan biopharmaceutical Co., Ltd, Wuxi, 214000, China

    Yue-ping Ding

  5. Zhangjiagang Xinchuang Biological Technology Co., Ltd, Zhenjiang, 212013, China

    Hong-Fei Liu

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  1. Yang Qu
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  2. Wen-Long Lai
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  4. Fei-Qin Zhu
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  5. Yuan Zhu
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  8. Ying Xu
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Correspondence to Ying Xu or Hong-Fei Liu.

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Qu, Y., Lai, WL., Xin, YR. et al. Development, Optimization, and Evaluation In Vitro/In Vivo of Oral Liquid System for Synchronized Sustained Release of Levodopa/Benserazide. AAPS PharmSciTech 20, 312 (2019). https://doi.org/10.1208/s12249-019-1511-z

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