A study of amorphous molecular dispersions of indomethacin and its sodium salt

Amorphous solid dispersions of indomethacin (IMC) and sodium indomethacin (NaIMC) over a range of compositions were prepared by physically mixing amorphous IMC and amorphous NaIMC, as well as by coprecipitation from methanol solution. Measurement of glass transition temperatures, T(g), for the physical mixtures revealed two values indicating, as expected, phase separation. In contrast, all samples of coprecipitated materials exhibited one value of T(g), which was greater than that predicted for ideal miscibility in the formation of a molecular dispersion. Such nonideality suggests a stronger acid-salt interaction in the amorphous state than that between acid-acid and salt-salt. FTIR spectroscopic analysis provides evidence for interactions between NaIMC and IMC through a combination of hydrogen bonding and ion-dipole interactions between the carboxylic group of the acid and the carboxylate anion of the salt. The inhibition of isothermal crystallization of IMC by NaIMC only when in molecular dispersion is believed to result from the interaction between the acid and the salt, which prevents the formation of hydrogen-bonded carboxylic acid dimers for IMC, required for the formation of crystal nuclei and crystallization.