Investigation of the milling-induced thermal behavior of crystalline and amorphous griseofulvin.
OBJECTIVE
To gain a better understanding of the physical state and the unusual thermal behavior of milled griseofulvin.


METHODS
Griseofulvin crystals and amorphous melt quench samples were milled in a vibrating ball mill for different times and then analyzed using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Modulated DSC (mDSC) and annealing studies were done for the milled amorphous samples to further probe the effects of milling.


RESULTS
Milling of griseofulvin crystals results in decrease in crystallinity and amorphization of the compound. A double peak is seen for crystallization in the DSC, which is also seen for the milled melt quench sample. Both enthalpy and temperature of crystallization decrease for the milled melt quenched sample. Tg is visible under the first peak with the mDSC, and annealing shows that increasing milling time results in faster crystallization upon storage.


CONCLUSIONS
Milling of griseofulvin results in the formation of an amorphous form and not a mesophase. It increases the amount of surface created and the overall energy of the amorphous griseofulvin, which leads to a decreased temperature of crystallization. The two exotherms in the DSC are due to some particles having nuclei on the surface.
Trasi
Niraj S
NS
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, USA.
Boerrigter
Stephan X M
SX
Byrn
Stephen Robert
SR
D003460:Crystallization; D004355:Drug Stability; D006118:Griseofulvin / Q000737:chemistry*; D015394:Molecular Structure; D010316:Particle Size; D011208:Powders; D013696:Temperature; D014961:X-Ray Diffraction
D011208:Powders; D006118:Griseofulvin