Rasmy Hanan E, Abouelmagd Sara A, Ibrahim Elsayed A
Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Institute for Drug Development and Innovation Research, Assiut University, Assiut, Egypt.
AAPS PharmSciTech. 2025 Jan 8;26(1):27. doi: 10.1208/s12249-024-03023-1.
Isoniazid (INH) and rifampicin (RIF) are the two main drugs used for the management of tuberculosis. They are often used as a fixed drug combination, but their delivery is challenged by suboptimal solubility and physical instability. This study explores the potential of active pharmaceutical ingredient-ionic liquids (API-ILs) to improve the physicochemical and pharmaceutical properties of INH and RIF. Antitubercular drugs, INH, or RIF, were paired with different counter ions (ascorbic acid (AsA), citric acid (CA), tartaric acid (TA), benzoic acid (BA), salicylic acid (SA), and p-amino salicylic acid (PAS)) using the solvent evaporation method. INH and RIF API-ILs were formed successfully using AsA and CA counter ions. IL formation was examined and analyzed using Fourier transform infrared (FTIR) spectroscopy, x-ray powder diffraction (XRPD), and polarized optical microscopy (POM). XRPD and POM confirmed their amorphous nature, while FTIR analysis demonstrated the contribution of hydrogen bonding to IL formation. IL formation enhanced the storage stability of the INH + RIF mixture in the presence of CA. Moreover, RIF-CA IL significantly increased the rate and extent of RIF dissolution. An effect that is unattainable with the RIF/CA physical mixture. Thus, API-IL formation not only enhances RIF dissolution but also facilitates the preparation of stable, compatible INH-RIF combinations.
异烟肼（INH）和利福平（RIF）是用于治疗结核病的两种主要药物。它们常以固定药物组合的形式使用，但其给药受到溶解度欠佳和物理稳定性的挑战。本研究探讨了活性药物成分 - 离子液体（API - ILs）改善INH和RIF的物理化学及药学性质的潜力。采用溶剂蒸发法将抗结核药物INH或RIF与不同的抗衡离子（抗坏血酸（AsA）、柠檬酸（CA）、酒石酸（TA）、苯甲酸（BA）、水杨酸（SA）和对氨基水杨酸（PAS））配对。使用AsA和CA抗衡离子成功形成了INH和RIF的API - ILs。使用傅里叶变换红外（FTIR）光谱、X射线粉末衍射（XRPD）和偏光显微镜（POM）对离子液体的形成进行了检测和分析。XRPD和POM证实了它们的非晶态性质，而FTIR分析表明氢键对离子液体形成的贡献。在CA存在的情况下，离子液体的形成增强了INH + RIF混合物的储存稳定性。此外，RIF - CA离子液体显著提高了RIF的溶解速率和程度。这是RIF/CA物理混合物无法实现的效果。因此，API - IL的形成不仅增强了RIF的溶解，还促进了稳定、相容的INH - RIF组合的制备。
