Mechanism of the intrinsic mechanism of the inflection point-the exploration of a "liquid film" hypothesis

The critical relative humidity (CRH) is an important indicator for measuring the hygroscopicity of solid drugs. The intrinsic mechanism of rapid moisture absorption of water-soluble drugs under CRH is not fully understood, and we conducted preliminary exploration on this topic. Firstly, the newly developed model tablet moisture absorption method and the traditional powder moisture absorption method were employed to determine the CRH values, an equivalence test between the two methods was conducted by a two-tailed t test. Then a conductivity meter was employed to measure the conductivity values of drug model tablets under different relative humidity (RH) conditions. As we know, anhydrous copper sulfate is a grayish white powder, which is easy to turn blue after absorbing water, based on this, this salt was selected as a model drug, and its CRH value was measured. Furthermore, anhydrous copper sulfate was compressed into tablets, then placed under different RH conditions. A series of photos were taken to record the formation process of the liquid film. The reason for the inflection point of the moisture absorption equilibrium curve was postulated based on changes in conductivity and color. The results showed that the CRH values of sucrose powders and tablets were 85.05% and 85.01%, respectively; and the CRH values of sodium citrate powders and tablets were 77.14% and 76.93% individually; the results of the two-tailed t test indicated that the two methods are equivalent. At RH of 75%, the conductivity of sodium citrate changed slightly, while at RH of 79% greater than the CRH, the conductivity underwent a sudden change. Sucrose and anhydrous copper sulfate showed a similar trend of change. In addition, the process of blue dots of anhydrous copper sulfate changing from discrete to continuous was successfully captured during the observation of moisture absorption. In summary, the aforementioned results suggest that the mechanism of the rising rapidly in moisture absorption curve of water-soluble drugs at CRH is probably attributed to the formation of a continuous aqueous "liquid film" on the drug surface during the process of moisture absorption.