Chikhalia V, Forbes R T, Storey R A, Ticehurst M
Drug Delivery Group, School of Pharmacy, University of Bradford, Bradford BD7 1DP, UK.
Eur J Pharm Sci. 2006 Jan;27(1):19-26. doi: 10.1016/j.ejps.2005.08.013. Epub 2005 Oct 24.
Milling is a key process in the preparation of many solid dosage forms. One possible milling induced change is the production of small levels of disorder or amorphous material found predominantly at the surface of a powder, which could lead to significant chemical and physical instability. The influence of crystal habit on this change was investigated using beta-succinic acid, in plate like and needle like morphologies. beta-Succinic acid crystals with these habits were processed in a ball mill and a jet mill. SEM images indicated jet milled material was finer than the ball milled product. Powder X-ray diffraction of the milled powders revealed an amorphous halo at lower angles and peak broadening suggesting disorder though this could not be quantified accurately. In addition, a partial conversion during milling to the alpha form was noted. Quantitation of the alpha form in the milled powders indicated it was present at <2% (w/w). Plate and needle shaped particles had similar heats of solution pre-milling, however, all milled powders had lower heats of solution compared to the unmilled powers. The contribution of the alpha polymorph to the lower heats of solution was calculated to be insignificant. Therefore, the reduced heat of solution is attributed to a loss in crystallinity. The largest decreases were seen in the plate like morphology. These findings suggest that beta-succinic acid crystals with plate like morphology are more prone to crystallinity loss on milling compared to the needle like morphology. The mill type has also been shown to influence the final crystallinity.
研磨是许多固体剂型制备过程中的关键环节。研磨可能导致的一种变化是产生少量无序或无定形物质，主要存在于粉末表面，这可能会导致显著的化学和物理不稳定性。使用片状和针状形态的β-琥珀酸研究了晶体习性对这种变化的影响。将具有这些习性的β-琥珀酸晶体在球磨机和气流粉碎机中进行处理。扫描电子显微镜图像表明，气流粉碎后的物料比球磨后的产品更细。研磨后粉末的粉末X射线衍射显示在较低角度出现无定形晕圈且峰变宽，表明存在无序状态，不过无法准确量化。此外，研磨过程中还观察到部分转化为α晶型。研磨后粉末中α晶型的定量分析表明其含量<2%（w/w）。片状和针状颗粒在研磨前具有相似的溶解热，然而，与未研磨的粉末相比，所有研磨后的粉末溶解热都较低。计算得出α多晶型对较低溶解热的贡献微不足道。因此，溶解热的降低归因于结晶度的损失。片状形态的结晶度损失最大。这些发现表明，与针状形态相比，片状形态的β-琥珀酸晶体在研磨时更容易发生结晶度损失。研磨类型也已被证明会影响最终的结晶度。
