Markeev Vladimir B, Blynskaya Evgenia V, Alekseev Konstantin V, Dorofeev Vladimir L, Marakhova Anna I, Vetcher Alexandre A
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 8 Baltiyskaya Str., 125315 Moscow, Russia.
Institute of Pharmacy and Biotechnology, Peoples' Friendship University of Russia n.a. P. Lumumba (RUDN), 6 Miklukho-Maklaya Str., 117198 Moscow, Russia.
Materials (Basel). 2025 Jan 6;18(1):203. doi: 10.3390/ma18010203.
Amorphous solid dispersion (ASD) technology is often used as a promising strategy to improve the solubility of active pharmaceutical ingredients (APIs). ASDs allow APIs to be dispersed at the molecular level in a polymer carrier, destroying the crystalline structure of the APIs and, thanks to the polymer, providing long-term supersaturation in solution. However, stability issues are an obstacle to the development of new medications with ASD. In addition to the molecular mobility at elevated temperatures leading to the crystallization of APIs, moisture affects the physical stability of ASD, leading to fractional separation and recrystallization. N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3) is an original API with both anxiolytic and antidepressant activity, but its insolubility in water can negatively affect (influence) bioavailability. Our study aims to create ASD GML-3 with moisture-resistant polymers (Soluplus, HPC) and assess the stability of the amorphous state of ASD after storage in high humidity conditions. As a result, HPC Klucel FX was revealed to be more stable than the brand, providing a high level of API release into the purified water environment and stability after 21 days (3 weeks) of storage in high humidity conditions.
无定形固体分散体（ASD）技术常被用作一种有前景的策略来提高活性药物成分（API）的溶解度。ASD能使API在聚合物载体中以分子水平分散，破坏API的晶体结构，并且借助聚合物在溶液中提供长期过饱和状态。然而，稳定性问题是ASD新型药物开发的一个障碍。除了高温下的分子运动导致API结晶外，水分也会影响ASD的物理稳定性，导致分层分离和重结晶。N-丁基-N-甲基-1-苯基吡咯并[1,2-a]吡嗪-3-甲酰胺（GML-3）是一种具有抗焦虑和抗抑郁活性的原创API，但其在水中的不溶性会对生物利用度产生负面影响。我们的研究旨在用防潮聚合物（固体分散体、羟丙基纤维素）制备GML-3的ASD，并评估在高湿度条件下储存后ASD无定形状态的稳定性。结果表明，羟丙基纤维素Klucel FX比该品牌更稳定，在高湿度条件下储存21天（3周）后，能在纯化水环境中实现高水平的API释放并保持稳定。
