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左旋多巴和卡比多巴新剂型多颗粒基质的药学及药代动力学评价

Pharmaceutical and pharmacokinetic evaluation of a newly formulated multiparticulate matrix of levodopa and carbidopa.

作者信息

Imbeah Emelia Priscilla, Adi-Dako Ofosua, N'guessan Benoit Banga, Kukuia Kennedy Kwami Edem, Dankyi Benedicta Obenewaa, Adams Ismaila, Ofori-Attah Ebenezer, Appiah-Opong Regina, Amponsah Seth Kwabena

机构信息

Department of Medical Pharmacology, University of Ghana Medical School, Accra, Ghana.

Department of Pharmaceutics and Microbiology, School of Pharmacy, University of Ghana, Accra, Ghana.

出版信息

ADMET DMPK. 2022 Oct 15;11(1):97-115. doi: 10.5599/admet.1474. eCollection 2023.

Abstract

Levodopa is routinely co-administered with carbidopa in the management of Parkinson's disease. Although the aforementioned combination therapy is effective, there may be fluctuating plasma levels of levodopa after oral administration. We formulated and evaluated the kinetic characteristics of the chitosan-pectin-based multiparticulate matrix of levodopa and carbidopa. Pectin was extracted from the cocoa husk, and the chitosan-pectin-based matrix was prepared by wet granulation. Formulations were evaluated for drug-excipient compatibility, drug content, precompression properties and in vitro release. For pharmacokinetic evaluation, rats were put into groups and administered either chitosan-pectin based matrix of levodopa/carbidopa, Sinemet CR or levodopa/carbidopa immediate release powder. Rats were administered the different formulations of levodopa/carbidopa (20/5 mg/kg) per os every 12 hours. The pharmacokinetic parameters of levodopa were estimated for the various treatment groups. The percentage content of levodopa and carbidopa in the various formulations was within the acceptance criteria. The AUC for levodopa/carbidopa multiparticulate matrix (Formulation 3: 484.98 ± 18.70 μg.hr/mL); Formulation 4: 535.60 ± 33.04 μg.hr/mL), and C (Formulation 3: 36.28 ± 1.52 μg/mL; Formulation 4: 34.80 ± 2.19 μg/mL) were higher than Sinemet CR (AUC 262.84 ± 16.73 μg.hr/mL and C 30.62 ± 3.37 μg/mL). The of the new formulation was longer compared to Sinemet CR.

摘要

左旋多巴在帕金森病的治疗中通常与卡比多巴联合使用。尽管上述联合疗法有效,但口服后左旋多巴的血浆水平可能会波动。我们制备并评估了基于壳聚糖-果胶的左旋多巴和卡比多巴多颗粒基质的动力学特征。从可可壳中提取果胶,并通过湿法制粒制备基于壳聚糖-果胶的基质。对制剂进行药物-辅料相容性、药物含量、压片前性质和体外释放评估。为进行药代动力学评估,将大鼠分组并给予基于壳聚糖-果胶的左旋多巴/卡比多巴基质、息宁控释片或左旋多巴/卡比多巴速释粉。每12小时经口给予大鼠不同配方的左旋多巴/卡比多巴(20/5 mg/kg)。估计各治疗组左旋多巴的药代动力学参数。各制剂中左旋多巴和卡比多巴的含量百分比在可接受标准范围内。左旋多巴/卡比多巴多颗粒基质(制剂3:484.98±18.70μg·hr/mL;制剂4:535.60±33.04μg·hr/mL)的AUC以及Cmax(制剂3:36.28±1.52μg/mL;制剂4:34.80±2.19μg/mL)均高于息宁控释片(AUC 262.84±16.73μg·hr/mL和Cmax 30.62±3.37μg/mL)。新制剂的t1/2比息宁控释片更长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7b/9909728/627cfeb56100/ADMET-11-1474-g001.jpg

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