Global Pharmaceutical Research & Development, Abbott Laboratories, 1401 Sheridan Road, North Chicago, Illinois, 60064, USA.
Pharm Res. 2012 Oct;29(10):2806-16. doi: 10.1007/s11095-012-0842-1. Epub 2012 Aug 8.
Milling and micronization of particles are routinely employed in the pharmaceutical industry to obtain small particles with desired particle size characteristics. The aim of this study is to demonstrate that particle shape is an important factor affecting the fracture mechanism in milling.
Needle-shaped crystals of the β polymorph of D-mannitol were prepared from recrystallization in water. A portion of the recrystallized materials was ball-milled. Unmilled and milled sieved fractions of recrystallized D-mannitol were analyzed by dynamic image analysis (DIA) and inverse gas chromatography (IGC) at finite concentration to explain the breakage/fracture behavior.
In the process of ball-milling, D-mannitol preferentially fractured along their shortest axis, exposing (011) plane with increased hydrophilicity and increased bounding rectangular aspect ratio. This is in contrary to attachment energy modeling which predicts a fracture mechanism across the (010) plane with increased hydrophobicity, and small change in particle shape.
Crystal size, and more importantly, crystal shape and facet-specific mechanical properties, can dictate the fracture/cleavage behavior of organic crystalline materials. Thorough understanding of the crystal slip systems, combining attachment energy prediction with particle shape and surface characterization using DIA and IGC, are important in understanding fracture behavior of organic crystalline solids in milling and micronization.
制药行业通常采用颗粒的粉碎和微粉化来获得具有所需粒径特征的小颗粒。本研究旨在证明颗粒形状是影响粉碎断裂机制的一个重要因素。
从水中重结晶制备 D-甘露醇β多晶型的针状晶体。一部分重结晶材料进行球磨。通过动态图像分析（DIA）和有限浓度下的反气相色谱（IGC）对未研磨和研磨过筛的重结晶 D-甘露醇进行分析，以解释断裂/破碎行为。
在球磨过程中，D-甘露醇优先沿着最短轴断裂，暴露具有增加亲水性和增加边界矩形纵横比的（011）面。这与附着能模型相反，该模型预测在增加疏水性和颗粒形状变化较小的情况下，断裂机制将穿过（010）面。
晶体尺寸，更重要的是晶体形状和特定晶面的机械性能，可以决定有机结晶材料的断裂/裂解行为。彻底了解晶体滑移系统，将附着能预测与使用 DIA 和 IGC 进行的颗粒形状和表面特性相结合，对于理解有机结晶固体在粉碎和微粉化过程中的断裂行为非常重要。
