Modeling of Parenteral Container Headspace Pressure

Abstract

When containers and related closure systems holding fluids are heated, internal pressures are generated. Depending upon conditions, surprisingly high pressures can be developed. These pressures are often sufficient to break system integrity. Numerous factors combine to determine the pressure generated within the container and closure system. Each of these factors can vary during the manufacture and service life of the product. Prudent pharmaceutical design seeks to set and control all the factors in such a manner that container and related closure integrity are maintained from the time of assembly to the time of use. Answers can be obtained by pure experimentation (“cut, try, recut, and retry until it comes out right”) or by predicting performance with a good mathematical model and testing once to verify the model. Pure experimentation requires extensive prototype parts and testing thereof. The mathematical model approach is more exact and produces a better product quicker and at lower cost. This paper uses a simple tubing vial to demonstrate the two approaches to controlling internal pressures from assembly to use. A mathematical model with experimental verification produces high confidence that the system integrity will be maintained as desired. The model used to predict the headspace pressure of the tubing vial is of significance in estimating performance of similar containers and related closures. It can rapidly produce product with predictable behavior. As such, the model is an excellent tool for designers of pharmaceutical products.