Development, Optimization, and Evaluation In Vitro/In Vivo of Oral Liquid System for Synchronized Sustained Release of Levodopa/Benserazide
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.
KEY WORDSlevodopa benserazide hydrochloride sustained release suspension cation-exchange resin prescription optimization
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].
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
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