Recrystallization of nifedipine and felodipine from amorphous molecular level solid dispersions containing poly(vinylpyrrolidone) and sorbed water.
OBJECTIVE
To compare the physical stability of amorphous molecular level solid dispersions of nifedipine and felodipine, in the presence of poly(vinylpyrrolidone) (PVP) and small amounts of moisture.


METHODS
Thin amorphous films of nifedipine and felodipine and amorphous molecular level solid dispersions with PVP were stored at various relative humidities (RH) and the nucleation rate was measured. The amount of water sorbed at each RH was measured using isothermal vapor sorption and glass transition temperatures (Tg) were determined using differential scanning calorimetry. The solubility of each compound in methyl pyrrolidone was measured as a function of water content.


RESULTS
Nifedipine crystallizes more easily than felodipine at any given polymer concentration and in the presence of moisture. The glass transition temperatures of each compound, alone and in the presence of PVP, are statistically equivalent at any given water content. The nifedipine systems are significantly more hygroscopic than the corresponding felodipine systems.


CONCLUSIONS
Variations in the physical stability of the two compounds could not be explained by differences in Tg. However, the relative physical stability is consistent with differences in the degree of supersaturation of each drug in the solid dispersion, treating the polymer and water as a co-solvent system for each drug compound.
Marsac
Patrick J
PJ
Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana, 47907 USA.
Konno
Hajime
H
Rumondor
Alfred C F
AC
Taylor
Lynne S
LS
D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D015736:Felodipine / Q000737:chemistry*; D006813:Humidity; D007700:Kinetics; D008956:Models, Chemical; D009543:Nifedipine / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D044366:Transition Temperature; D014867:Water / Q000737:chemistry*; D017155:Wettability
D012997:Solvents; D014867:Water; D011205:Povidone; D009543:Nifedipine; D015736:Felodipine