Solid-State Characteristics of Amorphous Sodium Indomethacin Relative to Its Free Acid |
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Authors: | Tong Ping Zografi George |
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Institution: | (1) School of Pharmacy, University of Wisconsin-Madison, 425 N. Charter St., Madison, Wisconsin, 53706 |
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Abstract: | Purpose. Having previously studied the amorphous properties of indomethacin (IN) as a model compound for drugs rendered amorphous during processing, we report on the formation and characterization of its sodium salt in the amorphous state and a comparison between the two systems.
Methods. Sodium indomethacin (SI) was subjected to lyophilization from aqueous solution, rapid precipitation from methanol solution, and dehydration followed by grinding to produce, in each case, a completely amorphous form. The amorphous form of SI was analyzed using DSC, XRD, thermomicroscopy and FTIR. The method of scanning rate dependence of the glass transition temperature, Tg, was used to estimate the fragility of the SI system. Enthalpy relaxation experiments were carried out to probe the molecular mobility of the SI system below Tg.
Results. The amorphous form of SI formed by different methods had a Tg equal to 121°C at a scanning rate of 20°C/min. This compares with a Tgfor indomethacin of 45°C. Estimation of fragility by the scanning rate dependence of Tg indicates no significant differences in fragility between ionized and unionized forms. Enthalpy relaxation measurements reveal very similar relaxation patterns between the two systems at the same degree of supercooling relative to their respective Tg values.
Conclusions. The amorphous form of SI made by various methods has a Tg that is about 75°C greater than that of IN, most likely because of the greater density and hence lower free volume of SI. Yet, the change of molecular mobility as a function of temperature relative to Tgis not very different between the ionized and unionized systems. |
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Keywords: | glass transition temperature amorphous systems molecular mobility fragility enthalpy relaxation |
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