Kajian Sistematis tentang Peptida Parenteral: Instabilitas, Mekanisme Degradasi, dan Strategi Formulasinya

Primawan Putra Nugrahadi, Christina Avanti
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Abstract

Abstract: The trend of using peptides, short chains of amino acids, as therapeutic agents has been increasing in recent decades. Therapeutic peptides usually use the parenteral route as systemic delivery system, requiring an aqueous formulation. However, in aqueous formulation, peptides are often unstable. The most stable form of therapeutic peptide is a lyophilized powder. Unfortunately, for tropical and developing countries such as Indonesia, as well as from pharmaco-economic point of view, if stable, peptide formulations in aqueous solution are preferred. This systematic literature review provides the various degradation pathways potentially experienced by therapeutic peptides available in Indonesia in aqueous solution. Then present various known strategies to prevent peptide degradation based on recent research. Article were searched on the PubMed, ScienceDirect, Wiley Online Library, and Google Scholar databases. Search results with keywords: therapeutic peptide OR peptide drug AND stability OR stabilization AND degradation OR degradation pathway found 20 articles that met the inclusion and exclusion criteria. Results showed that aggregation is the most common degradation pathway, followed by deamidation, hydrolysis, β-elimination, and disulphide exchange. The main strategies to improve peptide stability in solution are buffer selection and/or pH adjustment, addition of antioxidants/preservatives, combination of buffer with divalent metal ions, avoiding light exposure, and storage in cold temperature.
多孔肽的系统研究:其安装、降解机制和其配方策略
摘要:近几十年来,利用短链氨基酸肽作为治疗剂的趋势日益增加。治疗性多肽通常使用肠外途径作为全身给药系统,需要水制剂。然而,在水溶液中,多肽往往是不稳定的。最稳定的治疗肽形式是冻干粉。不幸的是,对于热带和发展中国家,如印度尼西亚,以及从药物经济学的角度来看,如果稳定,水溶液中的肽制剂是首选。这一系统的文献综述提供了各种降解途径可能经历治疗肽在水溶液中可用印度尼西亚。然后根据最近的研究提出了各种已知的防止肽降解的策略。文章在PubMed, ScienceDirect, Wiley Online Library和Google Scholar数据库中搜索。关键词:治疗性多肽或多肽药物,稳定性或稳定化,降解或降解途径,检索结果中有20篇文章符合纳入和排除标准。结果表明,聚合是最常见的降解途径,其次是脱酰胺、水解、β-消除和二硫交换。提高肽在溶液中的稳定性的主要策略是选择缓冲液和/或调整pH值、添加抗氧化剂/防腐剂、缓冲液与二价金属离子结合、避免光暴露和低温储存。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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