Solid-state study of mepivacaine hydrochloride.
Different crystalline forms of the local anaesthetic mepivacaine hydrochloride (MH) were revealed by Fourier transform infrared spectroscopy (FT-IR), not by conventional differential scanning calorimetry (DSC). The existence of two polymorphic anhydrous modifications was discovered and further characterized by X-ray powder diffraction and thermal analysis: Form II, the commercial one, and the more stable Form I, obtained by re-crystallization from Form II. Two pseudopolymorphs were also obtained: Form III, a solvate crystallized from ethanol and Form IV, a solvate crystallized from methanol. Single crystal X-ray diffraction data for both solvates were collected and their structures were determined. Form II, metastable and monotropically related to Form I, generates through desolvation of Form III, very often present in industrial processing, where crystallization from ethanol solution is a common practice. For the sake of clarity, the presence of polymorphic forms should be reported in the drug master files of MH. However, since MH is readily water soluble, the observed polymorphism has no relevance to its typical clinical use as aqueous solutions.
Giannellini
V
V
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via U. Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italia. valerio.giannellini@unifi.it
Bambagiotti-Alberti
M
M
Bartolucci
G
G
Bruni
B
B
Coran
S A
SA
Costantino
F
F
Di Vaira
M
M
D000779:Anesthetics, Local / Q000032:analysis / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002627:Chemistry, Physical; D006358:Hot Temperature; D008619:Mepivacaine / Q000032:analysis / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013696:Temperature; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D000779:Anesthetics, Local; D012997:Solvents; D008619:Mepivacaine