Estimation
of physical stability of amorphous solid dispersion using differential scanning
calorimetry |
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Authors: | Y Yoshihashi H Iijima E Yonemochi K Terada |
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Institution: | (1) Faculty of Pharmaceutical Sciences, Toho University, Chiba Japan, 274-8510, Miyama 2-2-1, Funabashi |
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Abstract: | The physical
stability of amorphous drug in solid dispersion was estimated using differential
scanning calorimetry (DSC). Tolbutamide (TB) and flurbiprofen (FBP) were selected
as insoluble drugs in water. Polyvinylpyrrolidone (PVP) was selected as a
polymer for solid dispersion. Solid dispersions of various ratios of TB or
FBP and PVP-K25 were prepared by solvent evaporation method and the induction
period of crystallization from amorphous drug in solid dispersion was measured
by DSC. Compared with FBP, the induction period of crystallization from TB
was delayed by an addition of PVP. The improvement of the physical stability
by the addition of PVP-K25 was estimated from the activation energy of diffusion
of drug molecules and the interfacial free energy between drug crystal and
supercooled liquid of drug in solid dispersion. From thses results, the hindrance
of the diffusivity of the drug molecule might be mainly affected the delay
of the induction period of crystallization of TB and FBP. |
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Keywords: | amorphous DSC flurbiprofen nucleation physical stability polyvinylpyrrolidone solid dispersion tolbutamide |
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