Photon Factory Activity Report 2016 #34 (2017)

BL-4B2/2015G660

PXRD Structure Analysis of Polymorphic Transformation ofMetoclopramide Crystals
1

Yuda Prasetya Nugraha1,* Haruki Sugiyama1, Hidehiro Uekusa1,*Tokyo Institute of Technology, Ookayama 2, Meguro-ku, Tokyo 152-8551, Japan

1 Introduction
Active pharmaceutical ingredients (APIs) often exist in
various crystalline forms such as polymorph, hydrates,and solvates. Understanding these crystalline forms arevery important because they commonly have different
physicochemical properties such as stability, compaction
properties, solubility, dissolution rate, and therefore
bioavailability. Furthermore, transformations between
different crystalline forms may occur during drug
manufacturing process or during storage of the final
dosage form. Hence, characterization of the structuralfeatures of each crystal form, their thermodynamic
relationship and physicochemical properties is essential
for pharmaceutical industry.
Single crystal X-ray diffraction is the most powerful
technique to reveal the structural properties in order tounderstand the mechanistic aspect of polymorphictransformation. However, in many cases, single crystalsof the parent compound tend to lose their integrity duringsolid-solid transformations, yielding a polycrystalline
product. Techniques to determine the crystal structure
directly from powder X-ray diffraction data have beendeveloped for organic materials in the last decades. These
techniques have been proved to be useful for establishing
the mechanism of polymorphic transformation.
Metoclopramide (MCP) is a substituted benzamide
medication mostly used for treatment of nausea andvomiting, gastroparesis, and gastroesophageal reflux
disease. MCP undergo transformation from the stableform I into the metastable form II by heating. Crystalstructure of form I of MCP has been reported. [1] In ourpresent work, we determined the crystal structure of form
II of MCP from high-resolution powder x-ray diffraction
data to understand the transformation process of MCP.

collection time was ~2h. The PXRD pattern of MCP form
II was indexed using X-Cell in Materials Studio 7.0(BIOVIA) and the space group was determined by
DICVOL06 in DASH package followed by the structure
solution. Rietveld refinement was performed in GSAS.
3 Results and Discussion
The profile fitting after final Rietveld refinement isshown in Figure 2.

Fig. 2: Profile fit of powder pattern after final Rietveld
refinement of form II of MCP.
The final Rietveld refinement gave the following
parameters: a=25.5766(11) Å, b=8.91631(19) Å,c=14.4337(3) Å, β=104.392(3)°, V=3188.3(2) Å3, C2/c,
Z=8, and Rwp=0.0924.
From the crystal structure, form II of MCP has
identical hydrogen bond chain with those observed inform I leading to a similar packing arrangement along baxis. These similar crystal packing is responsible for theease of the transformation of form II to the more stableform I in ambient condition.

References[1] M. Cesario et al., Eur. J. Med. Chem. 16, 13 (1981).
* uekusa@chem.titech.ac.jp
Fig. 1: Chemical Structure of Metoclopramide.
2 Experiment
Powder x-ray diffraction data of MCP form II wererecorded under ambient condition at Photon Factory BL4B2 multiple detector system (MDS) diffractometer(λ=1.197459(11) Å). Form II sample was prepared byheating the powder crystals of form I and packed into 2mm diameter borosilicate glass capillary tube. The data