Shelf drying is a common unit operation for reducing the liquid solvent content of solid cakes prior to material storage or downstream processing. Where the use of high temperatures could result in product stability issues, shelf dryers may employ vacuum to evaporate volatiles at low temperatures. Pharmaceutical manufacturing, for one, often requires efficient drying at less than ambient temperatures. The combination of shelf drying and sub-atmospheric pressure allows for efficient volatile material evaporation while maintaining the solid cake at relatively low temperatures. Determining the drying endpoint using in-process conditions that accurately predict the solid-cake moisture content minimizes the potential for a need to stop and restart the operation. We have found in a case study that the absolute pressure during a vacuum shelf drying operation correlates closely with the volatiles’ content of solid cake and, thus, can serve to regulate drying time.
In this case, we must dry a crystalline solid product to a specified solvent content prior to storage and shipping for downstream processing. Technicians load a batch of wet solids that contain 20–40-wt.% solvent into stainless steel pans. The pans then are placed on jacketed shelves within the dryer and thermocouples are inserted into thermowells installed on the pans to measure cake temperature. The dryer is connected to a vacuum pump separated by a block valve that controls the start and end of drying. The vacuum pump runs at capacity throughout drying, with a flow rate of 40–82 acfm depending upon the operating pressure. The dryer shelf contains recirculated water that is temperature controlled to a specified set point to regulate heat transfer to the pans. Figure 1 shows the dryer and Figure 2 depicts the equipment layout.
Drying starts once the dryer door is sealed and the vacuum supply valve is opened. The shelf transfers conductive heat to the cake. Pressure is measured on piping connecting the dryer to the vacuum pump. The pump runs at full capacity, both removing solvent vapors and continually decreasing the pressure within the dryer. Initial pressure is as high as 7 mm Hg abs., but typically falls to 0.1–0.5 mm Hg abs. by the end of the drying operation. The thermocouples installed into the trays continuously monitor the solid cake temperature. It drops quickly at the start of drying from ambient temperature to between -10°C and -25°C as a result of evaporative cooling. The rate of evaporative cooling is greatest at the start of the drying operation when the cake has its highest volatiles’ content. Temperature soon levels off and then slowly increases for the majority of the process due to the ever-decreasing rate of heat transfer from the solids to the vapor as the drying rate falls. By the end of drying, the cake temperature typically is 5–11°C when controlling the jacket to 12°C.
Control of the drying operation endpoint historically has been based on either a fixed time or a final cake temperature within a fixed time range. Both strategies heavily rely upon a defined time or time range to estimate when drying ends. A time-based approach poses inherent issues because factors that impact the drying rate vary from batch to batch and are difficult to control. The most influential factors are batch size or cake thickness, and initial moisture content.
Additionally, the temperature endpoint strategy has proven ineffective for several reasons. The level of leak rate into the dryer can impact the efficiency of solvent removal but is undetectable by the cake temperature alone. The placement of the temperature sensor within the cake also adds variability because the cake temperature changes as a function of its distance from the shelf. In addition, the cake isn’t uniform in initial moisture content, so a single-point temperature measurement within the cake isn’t always representative of the average of the entire cake due to lower or higher rates of localized evaporative cooling. These factors result in unacceptably high variability of endpoint moisture content.
In our case, prior to the vacuum dryer operation, the cake undergoes a forced nitrogen convection process that removes excess liquid solvent. As a result, the solvent contents observed in the process always start and end within the falling rate period of drying; therefore, the drying rate always is a function of the moisture content in the cake as mass transfer laws dictate. For this operation, batches enter the dryer with variable initial solid weights and liquid solvent contents. Batch size and the initial solvent content contribute to the volume of volatiles to be removed; larger or wetter batches generally require longer times to dry in the falling rate period of drying. Bigger batch sizes and, thus, thicker cakes also increase resistance to flow because diffusing vapor must travel a more torturous path to the surface. In addition, higher initial solvent content increases drying times because a greater ratio of initial solvent content to solid mass results both in a larger volume of solvent to remove and more-extensive evaporative cooling heat transfer occurring from the solids to the vapor. A higher extent of evaporative cooling removes heat from the solids and generates a lower temperature profile throughout the drying process, slowing the drying rate and extending the drying time.