Process control in freeze drying: determination of the end point of sublimation drying by an electronic moisture sensor.

Abstract

The end point of sublimation drying, or primary drying, is an important control point in the freeze drying process. Traditionally, the end of sublimation drying is determined by product temperature response, the rapid rise in product temperature after the temperature sensor loses thermal contact with ice being taken as evidence of the complete removal of ice from that container. However, the product temperature is measured by temperature sensors placed in a relatively small number of vials, and product in these vials can behave differently than the batch as a whole. There is clearly a need for an alternate method for end point detection which depends on a property of the batch as a whole. The partial pressure of water vapor in the drying chamber could serve as such a property. During sublimation drying, the partial pressure of water vapor in the drying chamber is high (close to the total pressure), but when the rapid evolution of water vapor ceases with the conclusion of sublimation drying, the partial pressure of water sharply decreases. In this research, an electronic moisture sensor is employed to monitor the partial pressure of water during the freeze drying process. The moisture sensor response provides a convenient and reliable method for determination of the end point of sublimation drying for the batch as a whole. The moisture sensor method has sufficient sensitivity to detect the presence of as few as 0.3% of the vials in a batch having residual ice.(ABSTRACT TRUNCATED AT 250 WORDS)