Department of Pharmaceutical Chemistry, University of Medical Sciences, Poznan, Poland.
Drug Dev Ind Pharm. 2013 Jan;39(1):51-61. doi: 10.3109/03639045.2012.657644. Epub 2012 Feb 20.
The compatibility studies of moexipril hydrochloride (MOXL), imidapril hydrochloride (IMD), enalapril maleate, (ENA) and lisinopril (LIS) in solid state with magnesium stearate and glyceryl behenate were performed.
The aim of this study was to detect any possible drug-excipient interactions in order to optimize technological process conditions by the selection of the most adequate lubricant.
Reversed-phase high-performance liquid chromatography was employed for studying drug-excipient binary mixtures in 1:1 ratio and pure drugs under forced ageing test conditions: temperature 318K (45 °C) and relative humidity range of 50.9%-75.4%. The method had been revalidated prior to use. The degradation rate constants for the binary mixtures and pure substances were calculated.
The experimental results evidenced that moexipril and enalapril degradation accorded with autocatalytic-second-order kinetics, imidapril degradation followed first-order reaction mechanism, and LIS followed reversible first-order reaction mechanism. A degradation pathway for each substance was proposed to account for the observed decomposition products. It was determined that moexipril stability decreased threefold in the presence of magnesium stearate indicating an incompatibility--(4.15 ± 0.12) 10(-3) compared to (1.43 ± 0.32) 10(-6) for moexipril in pure. No interaction between magnesium stearate and the remaining studied compounds was observed. The stability studies of MOXL-glyceryl behenate binary mixture revealed no interaction.
Magnesium stearate and increased relative humidity induce MOXL instability, while glyceryl behenate is an optimal lubricant, and therefore, it is recommended for moexipril-containing solid formulations. However, for the formulations containing moexipril and magnesium stearate, it is suggested to minimize the humidity level during storage.
对盐酸莫昔普利（MOXL）、盐酸依那普利（ENA）、盐酸咪达普利（IMD）和赖诺普利（LIS）与硬脂酸镁和山嵛酸甘油酯在固态下的相容性进行了研究。
本研究旨在检测任何可能的药物-赋形剂相互作用，以便通过选择最合适的润滑剂来优化工艺条件。
采用反相高效液相色谱法研究了 1:1 比例的药物-赋形剂二元混合物和在强制老化试验条件下的纯药物：温度 318K（45°C）和相对湿度范围为 50.9%-75.4%。在使用前对该方法进行了重新验证。计算了二元混合物和纯物质的降解速率常数。
实验结果表明，莫昔普利和依那普利的降解符合自催化二级动力学，咪达普利的降解遵循一级反应机制，而赖诺普利遵循可逆一级反应机制。提出了每种物质的降解途径来解释观察到的分解产物。结果表明，莫昔普利在硬脂酸镁存在下的稳定性降低了三倍，表明不兼容-（4.15±0.12）×10（-3）与莫昔普利在纯品中的（1.43±0.32）×10（-6）相比。未观察到硬脂酸镁与其余研究化合物之间的相互作用。莫昔普利-山嵛酸甘油酯二元混合物的稳定性研究表明没有相互作用。
硬脂酸镁和相对湿度的增加会导致莫昔普利不稳定，而山嵛酸甘油酯是一种理想的润滑剂，因此建议用于含有莫昔普利的固体制剂。然而，对于含有莫昔普利和硬脂酸镁的制剂，建议在储存过程中尽量降低湿度水平。
