Advances in Control of Production Freeze Dryers

Abstract

During the past decade, rapid changes in microelectronic technology have made the use of computers economically justifiable in processing applications which could not be justified previously. The concept of dedicated micro-computer control has become particularly attractive for small batch operations which require high lot-to-lot uniformity. Most pharmaceutical unit operations fall into this category, including lyophilization. Potential advantages of computer control are increased productivity, more consistent product quality, and improved process documentation. This presentation discusses methods of control of production freeze drying with emphasis on recent advances in instrumentation and control methodology. The concept of pressure control during freeze drying will be discussed, including a brief theoretical development, examples of the effect of pressure control on drying rate, and an overview of instrumentation for pressure measurement and control. The development of inexpensive microprocessor technology has caused a trend in production lyophilization control from manual cycle sequencing to total “hands-off” operation. A pilot freeze dryer which has been modified to operate under computer control is described. The system allows the operator to enter all parameters on a keyboard at the beginning of a cycle, thus permitting a complete freeze-dry cycle without operator intervention. The system stores pertinent process variables and events during the run for analysis and plot display following the cycle. The application of product electrical resistance as a method of characterizing formulations, developing freeze dry cycles, and its use in closed-loop control of production freeze drying is discussed.