Bates Simon, Zografi George, Engers David, Morris Kenneth, Crowley Kieran, Newman Ann
SSCI, Inc, 3065 Kent Ave, West Lafayette, Indiana 47906, USA.
Pharm Res. 2006 Oct;23(10):2333-49. doi: 10.1007/s11095-006-9086-2. Epub 2006 Sep 22.
The purpose of this paper is to provide a physical description of the amorphous state for pharmaceutical materials and to investigate the pharmaceutical implications. Techniques to elucidate structural differences in pharmaceutical solids exhibiting characteristic X-ray amorphous powder patterns are also presented.
The X-ray amorphous powder diffraction patterns of microcrystalline cellulose, indomethacin, and piroxicam were measured with laboratory XRPD instrumentation. Analysis of the data were carried out using a combination of direct methods, such as pair distribution functions (PDF), and indirect material modeling techniques including Rietveld, total scattering, and amorphous packing.
The observation of X-ray amorphous powder patterns may indicate the presence of amorphous, glassy or disordered nanocrystalline material in the sample. Rietveld modeling of microcrystalline cellulose (Avicel PH102) indicates that it is predominantly disordered crystalline cellulose Form Ibeta with some amorphous contribution. The average crystallite size of the disordered nanocrystalline cellulose was determined to be 10.9 nm. Total scattering modeling of ground samples of alpha, gamma, and delta crystal forms of indomethacin in combination with analysis of the PDFs provided a quantitative picture of the local structure during various stages of grinding. For all three polymorphs, with increased grinding time, a two-phase system, consisting of amorphous and crystalline material, continually transformed to a completely random close packed (RCP) amorphous structure. The same pattern of transformation was detected for the Form I polymorph of piroxicam. However, grinding of Form II of piroxicam initially produced a disordered phase that maintained the local packing of Form II but over a very short nanometer length scale. The initial disordered phase is consistent with continuous random network (CRN) glass material. This initial disordered phase was maintained to a critical point when a transition to a completely amorphous RCP structure occurred.
Treating X-ray amorphous powder patterns with different solid-state models, ranging from disordered nanocrystalline to glassy and amorphous, resulted in the assignment of structures in each of the systems examined. The pharmaceutical implications with respect to the stability of the solid are discussed.
本文旨在对药物材料的无定形状态进行物理描述，并研究其药学意义。还介绍了用于阐明呈现特征性X射线无定形粉末图谱的药物固体结构差异的技术。
使用实验室X射线粉末衍射仪（XRPD）测量微晶纤维素、吲哚美辛和吡罗昔康的X射线无定形粉末衍射图谱。采用直接方法（如对分布函数（PDF））和间接材料建模技术（包括Rietveld法、全散射和无定形堆积）相结合的方式对数据进行分析。
X射线无定形粉末图谱的观察结果可能表明样品中存在无定形、玻璃态或无序纳米晶材料。微晶纤维素（Avicel PH102）的Rietveld建模表明，它主要是无序的Iβ型结晶纤维素，有一些无定形成分。确定无序纳米晶纤维素的平均微晶尺寸为10.9nm。将吲哚美辛α、γ和δ晶型的研磨样品的全散射建模与PDF分析相结合，提供了研磨各阶段局部结构的定量图像。对于所有三种多晶型物，随着研磨时间的增加，由无定形和结晶材料组成的两相系统不断转变为完全随机密堆积（RCP）无定形结构。吡罗昔康I型多晶型物也检测到相同的转变模式。然而，吡罗昔康II型的研磨最初产生了一个无序相，该相在非常短的纳米长度尺度上保持了II型的局部堆积。初始无序相与连续随机网络（CRN）玻璃材料一致。当转变为完全无定形的RCP结构时，这个初始无序相一直保持到临界点。
用从无序纳米晶到玻璃态和无定形的不同固态模型处理X射线无定形粉末图谱，得到了所研究的每个系统中的结构归属。讨论了关于固体稳定性的药学意义。
