Using Moisture Sorption Isotherms to Determine the Total Water Content of a Lyophilized Product with Non-Destructive...

Traditional moisture determination methods are time-consuming and destructive. By generating its moisture sorption isotherm, non-destructive headspace water activity measurements can be used to determine the total moisture content for a particular drug product. In this study, a Dynamic Vapor Sorption (DVS) Instrument was used to generate a moisture sorption isotherm by varying the relative humidity (%RH) over the sample for a pre-determined range. The sample sorbs water at each relative humidity step and the change in mass of the sample as the water is sorbed is measured. The sample mass at the end of each relative humidity step is used to generate the isotherm, which is unique to each drug product. To confirm the validity of the moisture sorption isotherm, headspace water activity and Karl Fischer measurements were taken on the same samples and plotted alongside the isotherm. The good correlation that was observed between the isotherm and the corresponding water activity and KF measurements demonstrated that non-destructive water activity measurements can successfully be used to accurately infer the total moisture content of a lyophilized product. Furthermore, the non-destructive nature of the headspace water activity analysis allows rapid acquisition of a statistically relevant number of samples for each production batch.