Maclean Natalie, Khadra Ibrahim, Mann James, Williams Helen, Abbott Alexander, Mead Heather, Markl Daniel
Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Macclesfield, UK.
Int J Pharm X. 2021 Dec 9;4:100106. doi: 10.1016/j.ijpx.2021.100106. eCollection 2022 Dec.
Stability studies are an integral part of the drug development process for any drug product. In addition to monitoring chemical degradation, the physical stability of a drug product must also be evaluated to ensure that the drug release and performance is not affected by storage. In this study, directly compressed tablets of 16 different formulations were exposed to an accelerated stability program to quantify changes in tablet breaking force, porosity, contact angle and disintegration time. Tablets were exposed to five different storage conditions from 37 /30% relative humidity (RH) to 70 /75%RH with testing after 2 and 4 weeks of storage. Each formulation contained two different fillers (47% /w each), a disintegrant (5% /w) and magnesium stearate (1% w/w). The results show that tablets stored at high humidity show increases in porosity and decreases in tensile strength, particularly if they contain a highly hygroscopic filler such as microcrystalline cellulose (MCC). For tablets stored at high temperature, the most commonly affected property was the tablet wettability, measured by sessile drop contact angle measurements. These results are considered in combination with the performance-controlling disintegration mechanism (Maclean et al., 2021) to identify the critical properties which influence the performance after storage.
稳定性研究是任何药品研发过程中不可或缺的一部分。除了监测化学降解外,还必须评估药品的物理稳定性,以确保药物释放和性能不受储存的影响。在本研究中,将16种不同配方的直接压片置于加速稳定性试验中,以量化片剂的断裂力、孔隙率、接触角和崩解时间的变化。片剂在从37℃/30%相对湿度(RH)到70℃/75%RH的五种不同储存条件下放置,并在储存2周和4周后进行测试。每种配方包含两种不同的填充剂(各47%/w)、一种崩解剂(5%/w)和硬脂酸镁(1%w/w)。结果表明,储存在高湿度环境下的片剂孔隙率增加,拉伸强度降低,特别是当它们含有微晶纤维素(MCC)等高度吸湿的填充剂时。对于储存在高温下的片剂,最常受到影响的性质是片剂润湿性,通过静滴接触角测量来测定。结合性能控制崩解机制(Maclean等人,2021年)对这些结果进行考虑,以确定影响储存后性能的关键性质。