Statistical evaluation of vial design features that influence sublimation rates during primary drying.

PURPOSE

Understanding tubing vial design features that influence sublimation rate provides insight into the development of a more time and cost efficient lyophilization cycle.

METHODS

A Plackett-Burman screening experiment was initially used in evaluating multiple design features to predict those that have a statistically significant effect on sublimation rate. Sublimation rates of vials with intentional nominal and extreme dimensions were measured and directly correlated to glass vial design features using conservative and aggressive lyophilization parameters to amplify subtle differences in rates. Purified water, USP was used to alleviate the inhibition to mass transfer due to the presence of excipient and drug substances. Further studies quantified the effect of bottom concavity on sublimation rate while using model preparations to illustrate the impact of processing crystalline and amorphous material.

RESULTS

The results from the Plackett-Burman statistical screening experiment indicate that sublimation rate is influenced by glass type, vial diameter, bottom radius, and fill volume. Results from further studies verify that the influence of concavity on sublimation rate is statistically insignificant.

CONCLUSIONS

The results from the Plackett-Burman screening experiment reflect that vial diameter has the greatest impact on sublimation rate. Further studies confirm that various bottom concavities do not substantially influence sublimation rate.