An Investigation into the Polymorphism and Crystallization of Levetiracetam and the Stability of its Solid Form

Crystallization of Elusive Polymorphs of Meloxicam Informed by Crystal Structure Prediction

“…For every new molecule, solid form screening involving a series of long and costly crystallization experiments is a prerequisite for the development of a drug product, , yet it still does not guarantee that all possible polymorphic forms will be discovered and properly characterized. ,, On our road to fully govern the process of crystallizing a desired polymorphic form, we need to recognize the relationship between the crystal structure, crystal morphology, and energetics of a given form with crystallization conditions needed for its preparation . Meanwhile, especially among pharmaceutical patents, the literature is rich in polymorphic forms, posing serious difficulties in their crystallization, including reproducing experiments disclosed in patents’ examples or experimental protocols of scientific articles (see, for example, the cases of levetiracetam, meloxicam, and curcumin form III).…”

“…2,5,6 On our road to fully govern the process of crystallizing a desired polymorphic form, we need to recognize the relationship between the crystal structure, crystal morphology, and energetics of a given form with crystallization conditions needed for its preparation. 7 Meanwhile, especially among pharmaceutical patents, the literature is rich in polymorphic forms, posing serious difficulties in their crystallization, including reproducing experiments disclosed in patents' examples or experimental protocols of scientific articles (see, for example, the cases of levetiracetam, 8 meloxicam, 9 and curcumin form III 10 ).…”

Effect of Chirality on the Compression of 2-(2-Oxo-1-pyrrolidinyl)butyramide: A Tale of Two Crystals

“… 26 Form I (monoclinic, P 2 1 / c ) is stable below 303.5 K, and form II (monoclinic, P 2 1 / c ) is formed via a suspension of form I in methanol above 313 K. In contrast, despite several crystallization attempts, only one crystalline structure has been reported for the enantiopure S form, levetiracetam (Lev). 27 , 28 Given the extensive crystallization behavior of piracetam, it is possible that Lev and Eti show equally rich diagrams at high pressure.…”

“…Our inspiration to investigate this system was the extensive polymorphic behavior of piracetam (2-oxopyrrolidineacetamide, an analogous compound without the ethyl group). , It possesses three polymorphic forms at atmospheric pressure and two high-pressure forms as well as two hydrates. − 2-(2-Oxo-1-pyrrolidinyl)­butyramide crystallizes in two racemic polymorphs at atmospheric pressure (etiracetam, Eti) . Form I (monoclinic, P 2 1 / c ) is stable below 303.5 K, and form II (monoclinic, P 2 1 / c ) is formed via a suspension of form I in methanol above 313 K. In contrast, despite several crystallization attempts, only one crystalline structure has been reported for the enantiopure S form, levetiracetam (Lev). , Given the extensive crystallization behavior of piracetam, it is possible that Lev and Eti show equally rich diagrams at high pressure.…”