Modhave Dattatray, Barrios Brenda, Paudel Amrit
Research Center Pharmaceutical Engineering GmbH (RCPE), 8010 Graz, Austria.
Institute of Process and Particle Engineering, Graz University of Technology, 8010 Graz, Austria.
Pharmaceutics. 2019 Sep 3;11(9):457. doi: 10.3390/pharmaceutics11090457.
Reactive impurities, such as hydrogen peroxide in excipients, raise a great concern over the chemical stability of pharmaceutical products. Traditional screening methods of spiking impurities into solid drug-excipient mixtures oversimplify the micro-environment and the physical state of such impurities in real dosage form. This can lead to an inaccurate prediction of the long-term product stability. This study presents the feasibility of using a polyvinylpyrrolidone-hydrogen peroxide complex (PVP-HO) as an oxidative agent for the solid state forced degradation of a selected drug, vortioxetine HBr. The PVP-HO complex was prepared and characterized using FT-IR spectroscopy. The tablet compacts were made using a mixture of solid PVP-HO complex and crystalline vortioxetine HBr powder. The compacts were exposed to 40 °C/75% RH condition in open and closed states for different time intervals. The extent and the type of drug degradation were analysed using LC and LC-MS. The extent of degradation was higher in the samples stored at the open state as compared to the close state. The solution state forced oxidation was conducted to verify the peroxide induced degradation reactions. The results evidence the utility of the proposed solid-state stressor and the method for screening the sensitivity of drugs to the excipient reactive impurities involving peroxides in solid-state.
辅料中的活性杂质，如过氧化氢，引起了人们对药品化学稳定性的极大关注。传统的将杂质加入固体药物 - 辅料混合物中的筛选方法过度简化了实际剂型中此类杂质的微环境和物理状态。这可能导致对产品长期稳定性的预测不准确。本研究提出了使用聚乙烯吡咯烷酮 - 过氧化氢复合物（PVP - HO）作为氧化剂对选定药物氢溴酸伏硫西汀进行固态强制降解的可行性。制备了PVP - HO复合物并用傅里叶变换红外光谱进行了表征。片剂由固体PVP - HO复合物和结晶氢溴酸伏硫西汀粉末的混合物制成。将这些片剂在40°C/75%相对湿度条件下，分别在开放和封闭状态下放置不同时间间隔。使用液相色谱（LC）和液相色谱 - 质谱联用（LC - MS）分析药物降解的程度和类型。与封闭状态相比，开放状态下储存的样品降解程度更高。进行了溶液状态的强制氧化以验证过氧化物诱导的降解反应。结果证明了所提出的固态应激源以及用于筛选药物对固态中涉及过氧化物的辅料活性杂质敏感性的方法的实用性。
