Kunjir Sakshi, Pathare Prajakta, Sharma Sonam, Deoriya Jyoti, Natesan Subramanian, Malayandi Rajkumar
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hajipur, Export Promotion Industrial Park (EPIP), Zandaha Road, NH322, Hajipur, Bihar, 844102, India.
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, 700054, India.
Pharm Res. 2025 Jul 23. doi: 10.1007/s11095-025-03891-7.
The low aqueous solubility limits the therapeutic potential of both new and existing drug molecules. Mesalamine (MES), a primary therapeutic agent for inflammatory bowel diseases, has low aqueous solubility and incomplete dissolution in the colon; hence, it requires a high administered dose (maximum daily dose of 4.8 g/day). This study attempts to improve the dissolution velocity and solubility by designing MES nanocrystals.
MES nanocrystals were prepared using the dry ball milling (BM) process. MES nanocrystals (NCs) were prepared using Soluplus as stabilizer, and milling parameters were optimized to obtain the desirable particle size and other pharmaceutical attributes.
The prepared MES NCs were characterized to understand the influence of key milling parameters like time, speed, and stabilizer concentration. Variations in these parameters resulted in diverse morphologies, including rectangular bars, elongated hexagons, spheroids, and plates. Batch 29 (40/1/400) exhibited a plate-like crystal habit with a particle size of 435 nm and a PDI of 0.39, demonstrating an improved dissolution efficacy (84% in 60 min). Spectroscopic, microscopic, and thermal analyses confirmed the influence of ball milling on solubility, dissolution rate, particle size, and crystal habits.
The study outcomes could be useful for the successful scale-up and commercialization of drug products based on the dry BM platform technology.
低水溶性限制了新的和现有的药物分子的治疗潜力。美沙拉嗪（MES）是治疗炎症性肠病的主要药物，其水溶性低且在结肠中溶解不完全；因此，它需要高给药剂量（最大日剂量为4.8克/天）。本研究试图通过设计MES纳米晶体来提高溶解速度和溶解度。
采用干球磨（BM）工艺制备MES纳米晶体。以固体分散体聚合物Soluplus作为稳定剂制备MES纳米晶体（NCs），并优化研磨参数以获得所需的粒径和其他药物属性。
对制备的MES NCs进行表征，以了解关键研磨参数如时间、速度和稳定剂浓度的影响。这些参数的变化导致了不同的形态，包括矩形棒、细长六边形、球体和平板。第29批（40/1/400）呈现出片状晶体习性，粒径为435纳米，多分散指数（PDI）为0.39，显示出改善的溶解效果（60分钟内溶解84%）。光谱、显微镜和热分析证实了球磨对溶解度、溶解速率、粒径和晶体习性的影响。
该研究结果对于基于干球磨平台技术的药品成功放大生产和商业化可能是有用的。
