Campbell Roberts Sarra N, Williams Adrian C, Grimsey Ian M, Booth Steven W
Drug Delivery Group, School of Pharmacy, University of Bradford, West Yorkshire Bradford, UK.
J Pharm Biomed Anal. 2002 Jun 15;28(6):1149-59. doi: 10.1016/s0731-7085(02)00053-5.
Mannitol is a polymorphic parmaceutical excipient, which commonly exists in three forms: alpha, beta and delta. Each polymorph has a needle-like morphology, which can give preferred orientation effects when analysed by X-ray powder diffractometry (XRPD) thus providing difficulties for quantitative XRPD assessments. The occurrence of preferred orientation may be demonstrated by sample rotation and the consequent effects on X-ray data can be minimised by reducing the particle size. Using two particle size ranges (<125 and 125-500 microm), binary mixtures of beta and delta mannitol were prepared and the delta component was quantified. Samples were assayed in either a static or rotating sampling accessory. Rotation and reducing the particle size range to <125 microm halved the limits of detection and quantitation to 1 and 3.6%, respectively. Numerous potential sources of assay errors were investigated; sample packing and mixing errors contributed the greatest source of variation. However, the rotation of samples for both particle size ranges reduced the majority of assay errors examined. This study shows that coupling sample rotation with a particle size reduction minimises preferred orientation effects on assay accuracy, allowing discrimination of two very similar polymorphs at around the 1% level.
甘露醇是一种多晶型药物赋形剂，通常以三种形式存在：α型、β型和δ型。每种多晶型都具有针状形态，在用X射线粉末衍射仪（XRPD）分析时会产生择优取向效应，从而给XRPD定量评估带来困难。择优取向的出现可以通过样品旋转来证明，并且通过减小粒径可以将其对X射线数据的影响降至最低。使用两个粒径范围（<125和125 - 500微米），制备了β型和δ型甘露醇的二元混合物，并对δ组分进行了定量。样品在静态或旋转采样附件中进行分析。旋转并将粒径范围减小到<125微米，检测限和定量限分别减半至1%和3.6%。研究了许多潜在的分析误差来源；样品填充和混合误差是最大的变异来源。然而，两个粒径范围的样品旋转都减少了所研究的大部分分析误差。本研究表明，将样品旋转与粒径减小相结合可将择优取向对分析准确性的影响降至最低，从而能够在约1%的水平上区分两种非常相似的多晶型。
