Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract

Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

摘要 本研究旨在评估越橘叶粉提取物（bilberry leaf powder extract, BLPE）与为制备缓释（sustained-release, SR）片剂处方所遴选的6种药用辅料的相容性。本研究通过添加L-精氨酸与肌醇作为载体制备得到BLPE。采用热重-微分热重（TG-DTG）分析、傅里叶变换红外光谱（FTIR），并结合皮尔逊相关分析，对BLPE与各辅料按1:1比例配制的二元混合物的潜在相互作用进行检测。TG-DTG分析结果显示，BLPE与辅料的混合物的热行为存在一定偏差，但仅硬脂酸镁在混合物中的热行为与单一样品相比存在显著差异，提示该辅料与BLPE发生了化学相互作用。FTIR分析证实，BLPE与聚丙烯酸树脂L100（Eudragit L100）、甲基纤维素K4M（Methocel K4M）、甲基纤维素K100LV（Methocel K100LV）、微晶纤维素PH-101（Avicel PH-101）以及聚维酮S-630（Plasdone S-630）均具有良好相容性；而与硬脂酸镁形成的二元混合物则发生了固态化学相互作用。结合FTIR光谱结果推测，该相互作用会生成硬脂酸并使体系介质碱化。本研究结果不仅证明了TG-DTG分析可作为独立的热分析技术用于药用辅料与活性成分的相容性研究，同时验证了此前已有报道的碱性润滑剂（如硬脂酸盐）与含氨基活性成分之间的相互作用。