Solid State Characterization of E2101, A Novel Antispastic Drug

Kushida, Ikuo; Ashizawa, Kazuhide

doi:10.1002/jps.10211

Cited by 14 publications

(1 citation statement)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1) Polymorphs are known to give rise to significant differences in the physicochemical properties of the compound, which may have impacts on the stability, bioavailability and processability during manufacturing and/or in the final product. [2][3][4][5] In an extreme case, an undesired polymorph can even be toxic. 6) Because polymorphs have different lattice energies, the more energetic ones seek to revert to the most stable form during the kneading and tabletting processes.…”

mentioning

confidence: 99%

Solid State Characterizations and Analysis of Stability in Azelnidipine Polymorphs

Liu

Wang

Yang

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Azelnidipine, a new dihydropyridine calcium ion antagonist, was protected by patent in Japan. In present study, identifications of the crystal phases, including two polymorphic and a pseudopolymorphic crystal forms of azelnidipine, were attempted using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), IR-, Raman-, THz-, and ss-NMR-spectroscopy. PXRD identified three different crystal forms, while, spectroscopy analysis provided the information of crystal structure involving intermolecular interactions. The transition thermodynamics of the azelnidipine polymorphs were extensively investigated by solubility method. The solubility of the two polymorphs of α and β in 50% ethanol at 25, 31, 37, 42, and 49°C was investigated; the values obtained were used to calculate the thermodynamic parameters of the transition reaction. The temperature of polymorphic phase transition in 50% ethanol was 50.78°C, and the values of ΔG α,β θ , ΔH α,β θ , and ΔS α,β θ at 25°C were 1.18 kJ·mol 1 , 14.81 kJ·mol 1 , and 45.73 J·mol 1 ·K 1 , respectively. Form β was proved to be thermodynamic stable form at room temperature and enantiotropically related with form α. The kinetics of the solid-state decomposition, studied using DSC analysis, showed that the activation energies of decomposition of the polymorphs α and β at high temperatures were 148.67 and 151.93 kJ·mol 1 .Key words azelnidipine; polymorph; solid state NMR; THz spectrum; solubility; thermodynamics Polymorphs are different solid crystalline phases of the same drug or compound, which result from at least two different molecular arrangements of the compound in the solid state. In solvatomorphism, the formation of various crystals is the result of solvent molecules being incorporated in the crystal structure. A recent study estimated that 80-90% of organic compounds are capable of existing in polymorphic forms.

show abstract

mentioning

confidence: 99%