GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Int J Pharm. 2020 Apr 30;580:119218. doi: 10.1016/j.ijpharm.2020.119218. Epub 2020 Mar 9.
Excipient-moisture interaction can be a critical attribute in determination of product stability. This study aimed to investigate influence of integrating excipients having different moisture interaction into moisture sensitive drug formulations. Aspirin was formulated with maize starch (MS), microcrystalline cellulose (MCC) and calcium hydrogen phosphate dihydrate (DCP). The excipients were evaluated for their inherent moisture content and water activity. Tablets fabricated at different compression pressures were exposed to 40 °C, 75% relative humidity for a stipulated period before analyzing for aspirin degradation. The results revealed that while MS had higher moisture content, the water activity was relatively low. Consequently, MS tablets had lower aspirin degradation than MCC and DCP tablets. In contrast, high water activity of DCP resulted in greater aspirin degradation. This was despite the low moisture content of DCP. Influence of tablet porosity on aspirin degradation was minimal. This illustrated the fugacity of moisture, possessing high thermodynamic activity and physical spatial delimitation would not suppress its distribution. The findings suggested that excipients possessing high water retentive capacity could potentially be useful as internal tablet desiccants by acting as a moisture scavenger. This study also highlights the importance of water activity in preformulation studies related to the choice of excipients.
辅料-水分相互作用是决定产品稳定性的一个关键属性。本研究旨在考察将具有不同水分相互作用的辅料整合到水分敏感药物制剂中对其的影响。将玉米淀粉（MS）、微晶纤维素（MCC）和磷酸二氢钙二水合物（DCP）与阿司匹林一起配制。评估辅料的固有水分含量和水活度。在规定的时间内，将在不同压缩压力下制备的片剂在 40°C、75%相对湿度下暴露，然后分析阿司匹林的降解情况。结果表明，MS 的水分含量较高，但水活度相对较低。因此，MS 片剂的阿司匹林降解率低于 MCC 和 DCP 片剂。相比之下，DCP 的高水活度导致阿司匹林降解更多。尽管 DCP 的水分含量较低。片剂孔隙度对阿司匹林降解的影响很小。这说明具有高热力学活性和物理空间限制的水分逸度并不能抑制其分布。研究结果表明，具有高水分保持能力的辅料可以作为内部片剂干燥剂，通过作为水分清除剂来潜在地有用。本研究还强调了在与辅料选择相关的制剂前研究中水分活度的重要性。
