Influence of Milling Parameters on Crystal Morphology, Thermal Behavior, and Dissolution of Mesalamine Nanocrystals.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-07-23 DOI:10.1007/s11095-025-03891-7

Sakshi Kunjir, Prajakta Pathare, Sonam Sharma, Jyoti Deoriya, Subramanian Natesan, Rajkumar Malayandi

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引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: The study outcomes could be useful for the successful scale-up and commercialization of drug products based on the dry BM platform technology.

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铣削参数对美沙拉胺纳米晶形貌、热行为和溶解的影响。

目的：低水溶性限制了新药和现有药物分子的治疗潜力。美沙拉明（Mesalamine， MES）是炎症性肠病的主要治疗剂，在结肠中溶解度低且不完全溶解；因此，它需要高剂量给药（最大日剂量为4.8 g/天）。本研究试图通过设计MES纳米晶来提高溶解速度和溶解度。方法：采用干球磨法制备MES纳米晶。以Soluplus为稳定剂制备了MES纳米晶体（NCs），并优化了研磨参数以获得理想的粒径和其他药物属性。结果：对制备的MES nc进行表征，了解铣削时间、铣削速度、稳定剂浓度等关键参数对其的影响。这些参数的变化导致了不同的形态，包括矩形条，细长六边形，椭球体和板。第29批（40/1/400）显示出片状晶体习惯，粒径为435 nm， PDI为0.39，显示出提高的溶解效率（60分钟内84%）。光谱、微观和热分析证实了球磨对溶解度、溶解速率、粒度和晶体习性的影响。结论：本研究结果可为基于干燥BM平台技术的药品的成功规模化和商业化提供参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.