ORALS

Lyophilization/Freeze-drying is an essential technology for the production of stable dried pharmaceuticals with longer shelf life. Lyophilization produces porous product with a large surface area and high hygroscopicity. Although most current industrial pharmaceutical lyophilization are carried out in vial with rubber cap, moisture sorption remains a major problem during long-term storage in the range of year [1]. Moisture sorption is governed by the glass-rubber transition of the lyophilized matrix. Since this transition relates to the temperature and moisture content, the onset of transition is influenced by the balance between the fluidity of the matrix and the sorption rate. Therefore, a model strategy that relates the glass transition and moisture sorption kinetics to the humidity-induced-collapse is fundamental for quantitative prediction of the shelf-life of the lyophilized products [2], but such a model has not yet been reported. This study is to develop a new mathematical model of sorption kinetics applicable to glassy lyophilized matrices. By incorporating experimentally obtained moisture sorption isotherms and glass transition lines into the model development, it is shown that the time until the humidity-induced-collapse occurs can be predicted with higher accuracy. Results were visually summarized in stability maps as a function of the storage conditions, such as relative humidity and temperature. The location of the limit line, the border to induce humidity-induced-collapse, was observed to depend on the sorption rate constant, moisture sorption isotherm, and glass transition temperature of the selected material. As expected, matrices with relatively high transition temperatures exhibited a wider stability zone. The mathematical model proposed in this study could be a robust tool for quantitatively predicting product stability against storage conditions that reflect the properties of materials.

References:
[1] Matejtschuk, P., Rafiq, S., Johnes, S., Das, R.G., 2005. A comparison of vials with ampoules for the storage of biological reference materials. Biologicals 33, 63-70.\n[2] Duralliu, A., Matejtschuk, P., Williams, D.R., 2018. Humidity induced collapse in freeze dried cakes: a direct visualization study using DVS. European Journal of Pharmaceutics and Biopharmaceutics 127, 29-36.