(T0930-02-13) Influence of Temperature, Vacuum, and Humidity on Drying Kinetics of Citric Acid Monohydrate

Purpose: Vacuum drying is a widely used technique in the pharmaceutical and food industries for processing materials that are heat-sensitive, hygroscopic, or susceptible to oxidative degradation [1,2]. This method enables enhanced moisture removal at lower temperatures due to operation under reduced pressure, making it ideal for delicate compounds. However, the effects of specific process variables on the overall drying kinetics remain insufficiently characterized. This work examines the influence of temperature, pressure, and humidity on cake drying kinetics for citric acid monohydrate (CAM), a compound extensively used in pharmaceuticals and food, that transitions between monohydrate and anhydrous forms and is sensitive to heat [3].

Methods: Drying kinetics studies were carried out using a gravimetric device (Surface Measurement Systems, UK), a high-resolution instrument that precisely controls the pressure of vapours and gases around a small ( < 30 mg) amount of sample. The drying experiments were conducted under different conditions of temperature (25 °C and 40 °C), relative humidity (0% and 50 %) and pressure (1 atm and 0.5 atm). Nitrogen was used as the sample environment gas in all experiments. 10-20 mg of the samples were loaded in the sample pan of the DVS Vacuum and the mass change was recorded continuously until the mass of the sample remained constant. The rate of drying was then obtained by fitting linear region of mass loss percent vs time. The percent experimental mass loss of the sample was calculated from the mass difference between the start and end of experiment when no further mass loss occurred. The extent of drying of CAM was then calculated from the ratio of experimental mass loss to calculated mass loss for 100 % dehydration.

Results: Figure 1 shows the impact of temperature on drying under atmospheric pressure. Clearly, temperature has a predominant effect on the drying kinetics as well as extent of drying. The calculations indicate that raising the temperature from 25 °C to 40 °C (at 1 atm) increased the drying rate by a factor of 17.3 and improved dehydration extent from 32% to 91%. Figure 2 shows the impact of vacuum at different temperatures. At 25 °C the vacuum of 0.5 atm enhanced the drying rate by 1.78× and increased extent to 92%, versus 32% at atmospheric pressure. At 40 °C, vacuum contributed minimal further improvement. Figure 3 shows the impact of humidity on drying kinetics. At both 25 °C and 40 °C, increasing RH to 50% slowed drying rates by 3.5 to 4 times. The extent of dehydration also decreased at higher humidity, especially at 40 °C.

Conclusion: The drying behaviour of CAM is strongly influenced by environmental conditions. Temperature emerges as the most critical factor, with drying at 40 °C under dry atmospheric pressure achieving rates nearly 17 times higher than those at 25 °C, and also fully converting to the anhydrous phase. The use of vacuum at 25 °C also substantially enhances both the rate and extent of drying, although the relative benefit diminishes at elevated temperatures. Conversely, the presence of humidity markedly slows the drying process, reducing rates by approximately fourfold across all tested conditions. These findings highlight the necessity of carefully balancing temperature, vacuum, and humidity to optimize drying efficiency. Using milligram levels of the material, the instrument DVS Vacuum can provide such information critical to modelling vacuum drying process optimization at higher scales.

References: 1. Aigner, Isabella, et al. "Industrial-Scale Continuous Vacuum Drying of Active Pharmaceutical Ingredient Paste: Determination of the Process Window." Organic Process Research & Development 26.2 (2022): 323-334.
2. Tan, Choon Hui, et al. "Valorization of fruits, vegetables, and their by-products: Drying and bio-drying." Drying Technology 40.8 (2022): 1514-1538.
3. Lambros, Maria, et al. "Citric acid: A multifunctional pharmaceutical excipient." Pharmaceutics 14.5 (2022): 972.

Figure 1. Drying of CAM at 1 atm Nitrogen Flow and different temperatures.

Figure 2. Drying of CAM at 1 and 0.5 atm and (a) 25 oC (b) 40 oC

Figure 3. Drying of CAM at 0 and 50 % RH and temperature of (a) 25 oC (b) 40 oC