Thermodynamic and kinetic characterization of polymorphic transformation of famotidine during grinding.
Two polymorphs of famotidine were prepared by recrystallization from acetonitrile for form A and methanol for form B, respectively. The effect of grinding process on the polymorphic transformation of famotidine was investigated. Each famotidine sample ground for various grinding times in a ceramic mortar was determined by differential scanning calorimetry (DSC), conventional and thermal Fourier transform infrared (FT-IR) microspectroscopy. The results indicate that the raw material of famotidine was proved to be a form B. A unique IR absorption band at 3505 cm(-1) for famotidine form B gradually decreased its intensity with the grinding time, while two newer IR absorption bands at 3451 and 1671 cm(-1) for famotidine form A slowly appeared. The peak intensity ratio of 3451/350 5 cm(-1) was linearly (r=0.9901) increased with the grinding time, suggesting that the grinding process could induce the polymorphic transformation of famotidine from form B to form A by a zero-order process. The DSC endothermic peaks also confirmed this polymorphic transformation from famotidine form B (167 degrees C, DeltaH: 165J/g) to famotidine form A (174 degrees C, DeltaH: 148J/g) in which the values of enthalpy were linearly reduced with the increase of grinding time (r=0.9943). The phase transition temperature of the different ground famotidine samples could be easily and only evidenced by using thermal FT-IR microspectroscopy, rather than by DSC analysis. These phase transition temperatures of the famotidine form B ground for 5-20 min quickly reduced from 144 to 134 degrees C and maintained a constant at 134 degrees C even after 20-30 min grinding. The grinding process not only decreased the crystallinity of famotidine form B but also reduced the particle size of famotidine form B, resulting in easy induction of the polymorphic transformation of famotidine from form B to form A in ground famotidine sample.
Lin
Shan-Yang
SY
Department of Medical Research & Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. sylin@vghtpe.gov.tw
Cheng
Wen-Ting
WT
Wang
Shun-Li
SL
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004339:Drug Compounding; D005079:Excipients; D015738:Famotidine / Q000737:chemistry*; D006635:Histamine H2 Antagonists / Q000737:chemistry*; D007536:Isomerism; D007700:Kinetics; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
D005079:Excipients; D006635:Histamine H2 Antagonists; D015738:Famotidine