pH-solubility profiles of a model drug in salt form was established and the mechanism of salt-to-free base form transformation was investigated by increasing pH of the system. Wet massing experiments along with suspension experiments were used to investigate the effects of excipients on the stability of the salt form. It was found that nucleation of the free base did not occur at pHmax but that instead, a new boundary, the pHmetastable had to be reached before transformation occurred. It was also shown that some excipients impact the stability of the drug, this can help find excipients that previously would have been excluded on basis of a pH higher than pHmax but still lower than pHmetastable.
Chemical Engineering and Technology, 2014, Vol 37, Issue 8, p. 1347-1353
Pharmaceutical products; Drugs in salt form; Raman; Phase transformation; Excipient effects