Abstract
The purpose of this study was to evaluate the effect of processing and storage on the moisture content of two commercially available, 13-mm lyophilization stoppers designated as low moisture (LM) and high moisture (HM) uptake stoppers. The stopper moisture studies included the effect of steam sterilization time, drying time and temperature, equilibrium moisture content, lyophilization and moisture transfer from stopper to a model-lactose lyophilized cake. Results indicated that both stoppers absorbed significant amounts of moisture during sterilization and that the HM stopper absorbed significantly more water than the LM stopper. LM and HM stoppers required approximately 2 and 8 h drying at 105 °C, respectively, to achieve final moisture content of not more than 0.5 mg/stopper. Following drying, stopper moisture levels equilibrated rapidly to ambient storage conditions. The apparent equilibrium moisture level was approximately 7 times higher in the HM versus LM stopper. Freeze-drying had minimal effect on the moisture content of dried stoppers. Finally, moisture transfer from the stopper to the lyophilized product is dependent on the initial stopper water content and storage temperature. To better quantify the ramifications of stopper moisture, projections of moisture uptake over the shelf life of a drug product were calculated based on the product-contact surface area of stoppers. Attention to stopper storage conditions prior to use, in addition to processing steps, are necessary to minimize stability issues especially in low-fill, mass lyophilized products.
Footnotes
- Copyright © Parenteral Drug Association. All rights reserved.
PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.
If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.
Full issue PDFs are for PDA members only.
Note to pda.org users
The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.