An Investigation into the Polymorphism and Crystallization of Levetiracetam and the Stability of its Solid Form.
Levetiracetam (LEV) crystals were prepared using different solvents at different temperatures. The LEV crystals were systematically characterized by X-ray powder diffraction (XRPD) and morphological analysis. The results indicated that many kinds of crystal habits exist in a solid form of LEV. To investigate the effects of LEV concentration, crystallization temperature, and crystallization type on crystallization and solid phase transformation of LEV, multiple methods were performed for LEV aqueous solution to determine if a new solid form exists in solid-state LEV. However, XRPD data demonstrate that the LEV solid forms possess same spatial arrangements that are similar to the original solid form. This result indicates that the LEV concentration, crystallization temperature, and crystallization type in aqueous solution have no influence on the crystallization and solid phase transformation of LEV. Moreover, crystallization by sublimation, melt cooling, and quench cooling, as well as mechanical effect, did not result in the formation of new LEV solid state. During melt cooling, the transformation of solid form LEV is a direct process from melting amorphous phase to the original LEV crystal phase, and the conversion rate is very quick. In addition, stability investigation manifested that LEV solid state is very stable under various conditions.
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Kailin
K
Xu
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Xinnuo
X
Xiong
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Liuqi
L
Guo
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Lili
L
Wang
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Shanshan
S
Li
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Peixiao
P
Tang
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Jin
J
Yan
College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Di
D
Wu
College of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address: lihuilab@sina.com.
Hui
H
Li
D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D004355:Drug Stability; D000077287:Levetiracetam; D044367:Phase Transition; D010889:Piracetam / Q000031:analogs & derivatives* / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D014961:X-Ray Diffraction / Q000379:methods
D011208:Powders; D012997:Solvents; D000077287:Levetiracetam; D010889:Piracetam
X-ray powder diffractometry; crystals; levetiracetam; morphology; solid state; stability