目的 探究异烟肼口服溶液剂处方工艺对有关物质的影响,提高异烟肼口服溶液剂的稳定性。方法 建立有关物质检查方法并进行方法学验证,并以有关物质为指标,探究山梨醇、山梨酸钾和枸橼酸3种主要辅料在高温和光照条件下对异烟肼稳定性的影响,探究不同辅料添加顺序对制剂性状和有关物质的影响。结果 异烟肼有关物质检查方法能实现主药和杂质良好的分离,高温光照实验提示可相对性提升山梨醇浓度并控制pH在5~6,以降低异烟肼在液体分散体系中的降解;在制备过程中,将山梨酸钾、枸橼酸和异烟肼混合后再加入山梨醇,能够降低制备过程中异烟酸的产生。结论 本实验建立了异烟肼口服溶液剂有关物质检查方法,并通过处方和工艺的优化,为儿童结核病患者的治疗提供了1种潜在的选择。
Abstract
OBJECTIVE To study the effect of formulation and preparation on related substances and improve the photothermal stability of isoniazid oral solution. METHODS The self-control method without correction factor was used to establish the related substances test method, and which was verified. The related substances were used as indicators to study the effects of sorbitol, potassium sorbate and citric acid on the stability of isoniazid under thermal and photonic conditions. The different adding order of excipients was studied to get optimal preparation. RESULTS The good separation between isoniazid and impurities was performed by verified isoniazid related substances method. The photothermal condition experiment indicated that relative concentration of sorbitol can be increased, and the pH can be controlled at 5-6 to reduce the degradation of isoniazid in liquid dispersion system. In the preparation process, potassium sorbate, citric acid and isoniazid were mixed before adding sorbitol, which can reduce the production of isonicotinic acid. CONCLUSION The related substances test method is established and verified, and a potential choice is provided for the treatment of childhood tuberculosis by optimization of formulation and preparation.
关键词
儿童结核 /
异烟肼 /
口服溶液剂 /
有关物质 /
处方 /
制备工艺
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Key words
childhood tuberculosis /
isoniazid /
oral solution /
related substance /
formulation /
preparation process
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中图分类号：
R944
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参考文献
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脚注
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基金
十三五国家“重大新药创制”科技重大专项资助(2018ZX09721003-009-003;2018ZX09721003-007-007)
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