New solid modifications of nateglinide.
New modifications of the antidiabetic drug nateglinide were found and characterized by means of thermal analysis, vibrational spectroscopy and X-ray powder diffractometry. In particular it has been verified that the product obtained during the final steps of the nateglinide synthesis is the hemihydrate form which melts at about 86 degrees C provided that the adopted experimental conditions hinder the removal of the crystallization water. Otherwise, if the crystallization water is removed, the hemihydrate transforms to a new anhydrous polymorph that melts at 102.8 degrees C. The anhydrous polymorph, if stored at room temperature and humidity, gradually changes to H polymorph while, if stored in water vapour saturated atmosphere, it gets back water and reverts to the hemihydrate form. On the contrary, both an isothermal treatment at 80 degrees C and melt cooling bring to the B polymorph.
Bruni
G
G
C.S.G.I.-Dipartimento di Chimica Fisica M. Rolla, Università degli Studi di Pavia, Viale Taramelli 16, 27100 Pavia, Italy. giovanna.bruni@unipv.it
Berbenni
V
V
Milanese
C
C
Girella
A
A
Cardini
A
A
Lanfranconi
S
S
Marini
A
A
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D003510:Cyclohexanes / Q000138:chemical synthesis*; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D033362:Powder Diffraction; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D013818:Thermogravimetry; D044366:Transition Temperature; D014867:Water / Q000737:chemistry
D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D014867:Water; D000077715:Nateglinide; D010649:Phenylalanine