FAILURE OF GLASS VIALS DURING LYOPHILIZATION

Abstract

Lyophilization is a commonly used and often preferred method for the preparation of certain drug products. In this process, the liquid pharmaceutical product is packaged in glass vials, frozen and then dried via sublimation at low pressures. One of the problems that can be encountered during lyophilization is the occasional failure of the glass vial, a condition that will be referred to in this paper as “lyo-breakage”. Lyo-breakage, while relatively rare, can be a serious problem as it results in lost product, additional costs to remediate any spillage, and inspection time to ensure that all of the broken vials are discarded. Some companies have suggested that lyo-breakage is related to thermal stress and subsequently, can be reduced through changes to the thermal properties of the vials. It will be shown in this paper that when the most common form of lyo-breakage occurs, the stresses in the glass are caused by an internal force from product expansion during freezing and not due to thermal stress from processing temperatures.