A comparison of the physical stability of amorphous felodipine and nifedipine systems.
OBJECTIVE
The objective of this study was to investigate thermodynamic and kinetic factors contributing to differences in the isothermal nucleation rates of two structurally related calcium channel blockers, nifedipine and felodipine, both alone and in the presence of poly(vinylpyrrolidone) (PVP).


METHODS
Thin films of amorphous systems were cast onto glass slides and the nucleation rate was determined using optical microscopy. Enthalpy, entropy, and free energy of crystallization of the pure compounds were measured using differential scanning calorimetery (DSC). Molecular mobility and glass transition temperature of each amorphous system were characterized using DSC and hydrogen bonding patterns were analyzed with infrared spectroscopy. The composition dependence of the thermodynamic activity of the amorphous drug in the presence of the polymer was estimated using Flory-Huggins lattice theory.


RESULTS
Nifedipine crystallized more readily than felodipine from the metastable amorphous form both alone and in the presence of PVP despite having a similar glass transition temperature and molecular mobility. Nifedipine was found to have a larger enthalpic driving force for crystallization and a lower activation energy for nucleation.


CONCLUSIONS
The properties of the metastable form alone did not explain the greater propensity for nifedipine crystallization. When considering the physical stability of amorphous systems, it is important to also consider the properties of the crystalline counterpart.
Marsac
Patrick J
PJ
Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
Konno
Hajime
H
Taylor
Lynne S
LS
D002121:Calcium Channel Blockers / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D019277:Entropy; D015736:Felodipine / Q000737:chemistry*; D006860:Hydrogen Bonding; D007700:Kinetics; D008567:Membranes, Artificial; D009543:Nifedipine / Q000737:chemistry*; D010592:Pharmaceutic Aids / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013696:Temperature; D013816:Thermodynamics
D002121:Calcium Channel Blockers; D008567:Membranes, Artificial; D010592:Pharmaceutic Aids; D011205:Povidone; D009543:Nifedipine; D015736:Felodipine