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X-ray powder diffraction data for levetiracetam

Published online by Cambridge University Press:  10 October 2013

Kai Lin Xu ,
Bing Liang ,
Xiao Qing Wu ,
Li Li Zhang ,
Pei Xiao Tang  and
Hui Li
Kai Lin Xu
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Bing Liang
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Xiao Qing Wu
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Li Li Zhang
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Pei Xiao Tang
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
Hui Li*
Affiliation:
College of Chemical Engineering, Sichuan University, Chengdu 610065, China
*
a) Author to whom correspondence should be addressed. Electronic mail: lihuilab@sina.com
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Abstract

Experimental X-ray powder diffraction data, unit-cell parameters, and space group for levetiracetam, C8H14N2O2, are reported [a = 9.197(5) Å, b = 8.006(0) Å, c = 6.289(3) Å, β = 108.457(3)°, unit-cell volume V = 439.261 Å3, Z = 2, and space group P21]. All measured lines were indexed and are consistent with the P21 space group. No detectable impurity was observed.

Keywords

X-ray powder diffractionlevetiracetam
Type
New Diffraction Data
Information
Powder Diffraction , Volume 29 , Issue 1 , March 2014 , pp. 51 - 52
Copyright
Copyright © International Centre for Diffraction Data 2013 

I. INTRODUCTION

Levetiracetam (LEV, Figure 1), chemical name (S)-2-(2-oxopyrrolidin-1-yl) butanamide, an active single enantiomer (Haria et al., Reference Haria and Balfour1997), is an ethyl analog of the nootropic drug piracetam and used to treat certain types of seizures in people with epilepsy. It works by decreasing abnormal excitement in the brain and has minimal interactions with other anticonvulsants (Gualtieri et al., Reference Gualtieri, Manetti, Romanelli and Ghelardini2002). Compared with other antiepileptic drugs, levetiracetam has a unique mechanism for the treatment of epilepsy, satisfactory pharmacokinetic characteristics and efficiency with minimal side effects. Therefore, levetiracetam has been widely used in many countries at present.

Figure 1. Structural formula of levetiracetam.

The single-crystal structure of levetiracetam (a = 9.199 Å, b = 7.993 Å, c = 6.272 Å, β = 108.65°, unit-cell volume V = 436.962 Å3, Z = 2 and space group P21) was first reported by Song et al. (Reference Song, Lou, Li, Wu and Feng2003). But detailed X-ray powder diffraction data for levetiracetam have not been reported in the literature. In this report, the X-ray powder diffraction data of levetiracetam were collected, analyzed, and evaluated using the software package Material Studio 4.2 (Accelrys Co., Ltd. USA).

II. EXPERIMENTAL

A. Sample preparation

The title compound, levetiracetam (99% purity), in powder form was obtained from Zhejiang Jingxin Pharmaceutical Co., Ltd. The compound was re-crystallized in methanol (analytical grade) to obtain a single-crystal sample suiting for single-crystal measurement. The levetiracetam sample was also characterized by melting point and IR measurements.

B. Powder diffraction data collection and reduction

The diffraction pattern for the levetiracetam powder was collected at room temperature using an X'Pert PRO diffractometer (PANalytical) with an PIXcel 1D detector and CuKα 1 radiation (λ = 1.540 56 Å, generator setting: 40 kV and 40 mA). The diffraction data were collected in the angular range from 5 to 50° 2θ with a step size of 0.013 13° 2θ and a counting time of 30 s/step. Data evaluation was performed using the software package Material Studio 4.2 (Accelrys Co., Ltd. USA).

Through analyzing the peak positions in the powder XRD pattern by X-Cell method from “Powder Indexing”, the preliminary unit-cell parameters were obtained. The indexing results were then refined with the type of Pawley (Zhang et al., Reference Zhang, Pan, Xiao, Wu, Wang and Li2013), which involves assigning the Miller indices (h, k, l) to each observed peak in the experimental powder XRD pattern (Harris, Reference Harris2012). The conformation, position, and orientation of the trial model in a unit cell of levetiracetam were continuously regulated by MC/SA search algorithm in the Powder Solve package (Engel et al., Reference Engel, Wilke, König, Harris and Leusen1999). In order to obtain an optimal structure, variables defining the structural model and the powder diffraction profiles from the results of Powder Solve were refined by Rietveld refinement (Young, Reference Young1993) techniques based on the least squares methods. After Rietveld refinement, the final R wp of the structure was converged to 9.66%.

III. RESULTS

The experimental powder diffraction pattern is depicted in Figure 2. Indexing results confirmed that levetiracetam is monoclinic with space group P21 and unit-cell parameters: a = 9.197(5) Å, b = 8.006(0) Å, c = 6.289(3) Å, β = 108.457(3)°, unit-cell volume V = 439.261 Å3, Z = 2 and space group P21 (Table I). Using Rietveld refinement, the powder structure of levetiracetam was successfully determined.

Figure 2. X-ray powder diffraction pattern of the levetiracetam, using CuKα 1 radiation (λ = 1.540 56 Å).

Table I. Indexed X-ray powder diffraction data of levetiracetam, C8H14N2O2. Only the peaks with I ob s of 1 or greater are presented [a = 9.19(7) Å, b = 8.005(7) Å, c = 6.289(4) Å, β = 108.456(7)°, unit-cell volume V = 439.261 Å3, Z = 2, and space group P21]. All measured lines were indexed and are consistent with the P21 space group. The d-values were calculated using CuK α 1 radiation (λ = 1.540 56 Å).

Single-crystal data were also collected by Oxford Diffraction Xcalibur Nova system with MoKα radiation (λ = 0.710 73 Å) at room temperature and θ from 3.05 to 28.77°. The final results of the single-crystal levetiracetam were obtained and are in good agreement with those obtained by our X-ray powder diffraction analysis.

References

Engel, G. E., Wilke, S., König, O., Harris, K. D. M., and Leusen, F. J. J. (1999). “Powder Solve–a complete package for crystal structure solution from powder diffraction patterns,” J. Appl. Crystal. 32, 1169–1179.Google Scholar
Gualtieri, F., Manetti, D., Romanelli, M., and Ghelardini, C. (2002). “Design and study of piracetam-like nootropics, controversial members of the problematic of cognition-enhancing drugs,” Curr. Pharm. Des. 8, 125–138.Google Scholar
Haria, M., and Balfour, J. A. (1997). “Levetiracetam,” CNS Drugs. 7, 159–164.Google Scholar
Harris, K. D. M. (2012). “Powder diffraction crystallography of molecular solids,” Top. Curr. Chem. 315, 133–178.Google Scholar
Song, J., Lou, K. X., Li, X. J., Wu, X. P., and Feng, R. X. (2003). “2-(2-Oxopyrrolidin-1-yl) butyramide,” Acta Crystallogr., Sect. E (structure Rep. Online). 59, 1772.Google Scholar
Young, R. A. (1993). The Rietveld Method, IUCr Monographies of Crystallography (Wiley, Oxford).Google Scholar
Zhang, L. L., Pan, Q. Q., Xiao, D., Wu, X. Q., Wang, Q., and Li, H. (2013). “X-ray powder diffraction data for deoxyschisandrin,” Powder Diffr. 28, 231–233.Google Scholar
Figure 0

Figure 1. Structural formula of levetiracetam.

Figure 1

Figure 2. X-ray powder diffraction pattern of the levetiracetam, using CuKα1 radiation (λ = 1.540 56 Å).

Figure 2

Table I. Indexed X-ray powder diffraction data of levetiracetam, C8H14N2O2. Only the peaks with Iobs of 1 or greater are presented [a = 9.19(7) Å, b = 8.005(7) Å, c = 6.289(4) Å, β = 108.456(7)°, unit-cell volume V = 439.261 Å3, Z = 2, and space group P21]. All measured lines were indexed and are consistent with the P21 space group. The d-values were calculated using CuK α1 radiation (λ = 1.540 56 Å).