Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455; Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46225.
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455; Characterization Facility, University of Minnesota, Minneapolis, Minnesota 55455.
J Pharm Sci. 2019 Jan;108(1):476-484. doi: 10.1016/j.xphs.2018.09.015. Epub 2018 Sep 21.
Our goals were to evaluate the effects of (i) hydrostatic pressure alone and (ii) its combined effect with shear stress during compaction, on the polymorphic transformation (form C → A) of a model drug, chlorpropamide. The powder was either subjected to hydrostatic pressure in a pressure vessel or compressed in a tablet press, at pressures ranging from 25 to 150 MPa. The overall extent of phase transformation was determined by powder X-ray diffractometry, whereas 2D-X-ray diffractometry enabled quantification of the spatial distribution of phase composition in tablets. Irrespective of the pressure, the extent of transformation following compaction was higher than that because of hydrostatic pressure alone, the difference attributed to the contribution of shear stress experienced during compaction. At a compression pressure of 25 MPa, there was a pronounced gradient in the extent of phase transformation when monitored from radial tablet surface to core. This gradient decreased with increase in compression pressure. Four approaches were attempted to minimize the effect of compression-induced phase transformation: (a) site-specific lubrication, (b) use of a viscoelastic excipient, (c) ceramic-lined die, and (d) use of cavity tablet. The ceramic-lined die coupled with site-specific lubrication was most effective in minimizing the extent of compression-induced phase transformation.
我们的目的是评估（i）静压单独作用和（ii）其与压缩过程中的切应力联合作用对模型药物氯苯丙脲多晶型转变（形式 C→A）的影响。粉末要么在压力容器中承受静压，要么在压片机中在 25 至 150 MPa 的压力下压缩。粉末 X 射线衍射法用于确定相转变的整体程度，而 2D-X 射线衍射法则能够定量评估片剂中相组成的空间分布。无论压力如何，压缩后发生的转变程度都高于单纯静压引起的转变程度，这种差异归因于压缩过程中经历的切应力的贡献。在压缩压力为 25 MPa 时，从径向片剂表面到核心监测到的相转变程度存在明显的梯度。随着压缩压力的增加，该梯度减小。为了最小化压缩诱导的相转变的影响，我们尝试了四种方法：（a）定点润滑，（b）使用粘弹性赋形剂，（c）陶瓷衬里模具，和（d）使用腔式片剂。陶瓷衬里模具与定点润滑相结合是最小化压缩诱导相转变程度最有效的方法。
