Kuwata Aya, Ishikawa Agata, Ono Tetsuo, Yonemochi Etsuo
Research & Development Headquarters Self-Medication, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-Cho, Kita-ku, Saitama 331-9530, Japan.
Department of Physical Chemistry, Hoshi University, 2-4-41 Ebara, Tokyo 142-0063, Japan.
Pharmaceutics. 2025 Apr 1;17(4):455. doi: 10.3390/pharmaceutics17040455.
We investigated the compression mechanisms for loxoprofen sodium (LXP), which is known to occur as a dihydrate, and identified parameters that influence the tablet hardness of LXP tablets prepared by the wet granulation method. LXP granules were prepared with water or ethanol as the solvent, dried under various conditions and sieved for particle size control, with 1% Mg-st added before tablet compression. : The findings indicated that both the granulation solvent and drying temperature significantly impacted the tablet hardness. Granules prepared with ethanol exhibited higher hardness as compared with those prepared with water. The tablet hardness varied with varying drying temperatures. Principal component analysis (PCA) identified positive correlations between the tablet hardness and the surface free energy (SFE), polar component (γ(p)), and cohesion, and a negative correlation with the dispersive component (γ(d)). Granules prepared with ethanol exhibited a higher γ(p), likely due to the differing solubility in ethanol and water, leading to enhanced interparticle binding. This study confirmed that use of the eutectic mixture of LXP and Mg-st exerted no significant influence. Crystal structure analysis indicated that the hydration states varied according to the drying temperature, suggesting the higher γ(p) in anhydrous forms, due to the lower hydrophobicity, contributed to increased tablet hardness. This research offers insights for optimizing the formulation conditions to improve the LXP tablet hardness. Appropriate selection of the solvent and drying temperature mitigates tablet hardness issues, while assessment of SFE can help in the selection of suitable additives.
我们研究了已知以二水合物形式存在的洛索洛芬钠（LXP）的压缩机制，并确定了影响通过湿法制粒法制备的LXP片剂硬度的参数。以水或乙醇为溶剂制备LXP颗粒，在各种条件下干燥并筛分以控制粒径，在压片前添加1%的硬脂酸镁。研究结果表明，制粒溶剂和干燥温度均对片剂硬度有显著影响。与用水制备的颗粒相比，用乙醇制备的颗粒表现出更高的硬度。片剂硬度随干燥温度的变化而变化。主成分分析（PCA）确定片剂硬度与表面自由能（SFE）、极性成分（γ(p)）和内聚力之间呈正相关，与分散成分（γ(d)）呈负相关。用乙醇制备的颗粒表现出较高的γ(p)，这可能是由于在乙醇和水中的溶解度不同，导致颗粒间结合增强。本研究证实，使用LXP与硬脂酸镁的低共熔混合物没有显著影响。晶体结构分析表明，水合状态随干燥温度而变化，这表明无水形式中较高的γ(p)由于较低的疏水性而有助于提高片剂硬度。本研究为优化配方条件以提高LXP片剂硬度提供了见解。适当选择溶剂和干燥温度可缓解片剂硬度问题，而评估SFE有助于选择合适的添加剂。
