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. 2021 Jun 15;603:120690. doi: 10.1016/j.ijpharm.2021.120690. Epub 2021 May 7.
Physicochemical and mechanical properties of tablets are largely dictated by formulation compositions. Different excipients possess different tableting and moisture sorption behaviors. Therefore, this study was designed to elucidate the relative influence of the proportion of components in formulations on tablet properties. Acetylsalicylic acid (ASA) tablets containing different proportions of starch, microcrystalline cellulose (MCC) and calcium hydrogen phosphate dihydrate (DCP) were prepared. The excipients were evaluated for their moisture sorption properties. Mechanical strength of the tablets was determined alongside with ASA stability, by storing the tablets at 75% RH, 25 °C. The stability study showed the importance of drug loading level on its stability. For a fixed ASA proportion, formulations with more starch were able to absorb more moisture and possessed larger areas of hysteresis loop in their moisture sorption isotherms. The presence of starch contributed positively to ASA stability although increasing proportions of starch compromised the tablet mechanical properties. Contrastingly, MCC produced mechanically stronger tablets as its plastically deforming and fibrous properties contributed to a good structural network. The findings provide a deeper understanding of the dichotomous effect by the proportion of components in formulations containing a moisture sensitive drug on drug stability and mechanical strength of the resultant tablets.
片剂的物理化学和机械性能在很大程度上取决于配方组成。不同的赋形剂具有不同的压片和吸湿行为。因此，本研究旨在阐明配方中各成分比例对片剂性质的相对影响。制备了含有不同比例淀粉、微晶纤维素（MCC）和磷酸二氢钙二水合物（DCP）的阿司匹林（ASA）片。评估了赋形剂的吸湿性能。通过将片剂储存在 75%RH、25°C 下，测定了片剂的机械强度和 ASA 的稳定性。稳定性研究表明药物载药量对其稳定性的重要性。对于固定的 ASA 比例，含有更多淀粉的配方能够吸收更多的水分，并在其吸湿等温线上具有更大的滞后环面积。淀粉的存在对 ASA 的稳定性有积极的影响，尽管淀粉的比例增加会损害片剂的机械性能。相比之下，MCC 产生了机械强度更高的片剂，因为其塑性变形和纤维特性有助于形成良好的结构网络。研究结果深入了解了含有水分敏感药物的配方中各成分比例对药物稳定性和所得片剂机械强度的双重影响。
