Amy Miller & Jennifer Riter

Analytical Lab Services

April 09, 2012

Evaluation of residual moisture in lyocakes and corresponding lyophilization stoppers of different rubber formulations

Dr. Heike Kofler, Amy Miller, Jennifer Riter
West Pharmaceutical Services, Inc.

One of the critical success factors for packaging lyophilized drugs is protection against product degradation caused by moisture. Moisture can be introduced into a lyophilized drug product cake from the elastomeric stopper and from the atmospheric headspace; it can also permeate through the stopper, a process known as moisture transmission.

To better understand moisture transmission and retention, West performed a three-year study to determine the effects of autoclave and drying times on residual moisture in lyophilization stoppers. Lyophilized lactose was also evaluated to determine the ability of lyophilization stoppers to protect drug product from moisture absorption.

Lyophilization stoppers have been designed to permit proper lyophilization of drug product in a lyophilization chamber. Prior to packaging the drug product, many of these stoppers are washed and steam sterilized, which may increase moisture content within the stopper, and then dried to drive out the moisture in the stopper. If the drying conditions for the stopper are not optimized, residual moisture can transfer into the lyophilized drug product over time. Lyophilized drug product is often unstable in its aqueous form. Therefore, moisture from the lyophilization stopper may have a detrimental effect on the drug product. This study, conducted by West Analytical Services, was performed to determine the moisture content of lyophilization stoppers exposed to a typical autoclave sterilization cycle and dried for 1, 4, and 8 hours. The lyophilization stoppers were exposed to typical lyophilization parameters to determine if the stopper transfers moisture. The stoppers evaluated were made from two types of chlorobutyl, bromobutyl and butyl base polymers. They were either fluoropolymer laminated (chlorobutyl 1, chlorobutyl 2, bromobutyl, butyl) or non-laminated (chlorobutyl 1). The study should help manufacturers choose a suitable stopper for moisture-sensitive lyophilized drug products.

The data revealed that a 1-hour drying cycle was not enough to remove the moisture driven into the stopper during the autoclave cycle. It was necessary to dry each stopper for at least 4 hours to return the moisture content in the stopper to the amount of moisture prior to steam sterilization. The residual moisture within the stoppers increased over time and leveled off around 18 or 24 months. The moisture content of the lactose increased over time as well and there was a slight increase in the moisture percentage of the lactose from 24 to 36 months. Best results were gained with an 8-hour drying time.

Read the full scientific poster here.