GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Airlangga University, Kampus C Mulyorejo, Surabaya 60115, Indonesia.
Mol Pharm. 2024 May 6;21(5):2484-2500. doi: 10.1021/acs.molpharmaceut.4c00031. Epub 2024 Apr 22.
Excipients are ubiquitous in pharmaceutical products, and often, they can also play a critical role in maintaining product quality. For a product containing a moisture-sensitive drug, moisture can be deleterious to the product stability during storage. Therefore, using excipients that interact with moisture in situ can potentially alleviate product stability issues. In this study, the interactive behavior of starch with moisture was augmented by coprocessing maize starch with sodium chloride (NaCl) or magnesium nitrate hexahydrate [Mg(NO)·6HO] at different concentrations (5 and 10%, w/w). The effect of the formulation on drug stability was assessed through the degradation of acetylsalicylic acid, which was used as the model drug. The results showed that coprocessing of the starch with either NaCl or Mg(NO)·6HO impacted the number of water molecule binding sites on the starch and how the sorbed moisture was distributed. The coprocessed excipients also resulted in lower drug degradation and lesser changes in tablet tensile strength during post-compaction storage. However, corresponding tablet formulations containing physical mixtures of starch and salts did not yield promising outcomes. This study demonstrated the advantageous concomitant use of common excipients by coprocessing to synergistically mitigate the adverse effects of moisture and promote product stability when formulating a moisture-sensitive drug. In addition, the findings could help to improve the understanding of moisture-excipient interactions and allow for the judicious choice of excipients when designing formulations containing moisture-sensitive drugs.
辅料在药物产品中无处不在，而且往往在维持产品质量方面也起着至关重要的作用。对于含有对湿度敏感药物的产品来说，水分在储存过程中会对产品稳定性造成损害。因此，使用能够与水分原位相互作用的辅料，可能有助于缓解产品稳定性问题。在这项研究中，通过在不同浓度（5%和 10%，w/w）下将玉米淀粉与氯化钠（NaCl）或六水合硝酸镁[Mg（NO）·6HO]共加工，增强了淀粉与水分的相互作用行为。通过乙酰水杨酸的降解来评估配方对药物稳定性的影响，乙酰水杨酸被用作模型药物。结果表明，淀粉与 NaCl 或 Mg（NO）·6HO 共加工会影响淀粉上结合水分子的数量以及被吸附水分的分布方式。共加工的辅料还会导致药物降解率降低，以及在压实后储存期间片剂拉伸强度变化更小。然而，含有淀粉和盐的物理混合物的相应片剂配方并未产生令人满意的结果。本研究通过共加工有利地结合了常见辅料的使用，以协同减轻水分的不利影响，并在制定对湿度敏感药物的配方时促进产品稳定性。此外，这些发现有助于提高对水分-辅料相互作用的理解，并在设计含有对湿度敏感药物的配方时合理选择辅料。
