Hygroscopic Study of Glucose, Citric Acid, and Sorbitol Using an Electrodynamic Balance: Comparison with UNIFAC Predictions

Abstract

The equilibrium water sorption and desorption characteristics of three pharmaceutical excipients, namely, glucose, citric acid, and sorbitol, were investigated at 25 ± C using an electrodynamic balance (EDB). The mass fraction of solute (mfs), de ned as the ratio of the dry solute mass to the solution mass, of the additives was measured as a function of relative humidity (RH) at equilibrium. Bulk measurements and literature data suggest that these three additives all crystallize at their respective saturation conditions. However, crystallization or deliquescence was not observed for the suspended particles of the three additives. They behave as nondeliquescent materials and sorb and desorb water reversibly. At RH = 5%, citric acid particles still contain » 8 wt% residual water, which corresponds to a stoichiometry of citric acid monohydrate. Glucose and sorbitol particles are essentially water-free. Universal Functional Activity Coef cient (UNIFAC) model predicts the water activities of glucose, citric acid, and sorbitol (expressed as mfs of the particles) to within § 16%, 24%, and 6% of those determined by the EDB, respectively.

Properties of Citric Acid and Its Solutions

“…Water activities of citric solutions were determined by the isopiestic and isotenoscopic methods [89,93] and recently by applying the electronic hygrometer [144][145][146][147][148], the electrodynamic balance (EDB) [144] and the hygroscopicity tandem differential mobility analyzer (HTDMA) [149]. By using EDB and HTDMA equipment, the hygroscopicity cycles including hydration and dehydration of solid particles can be observed.…”

“…Such measurements were performed in the context of hygroscopic properties of pharmaceutical solids, atmospheric aerosols and foodrelated solutions. Vapour pressures of water over citric acid solutions at 25 °C are known for different concentration ranges from investigations of Levien [89], Apelblat et al [93], Velezmoro and Meirelles [145,146], Peng et al [144], Maffia [147,148] and Zardini et al [149]. Velezmoro [146] measured water activities at 30 and 35 °C, Apelblat et al [93] from 30 to 45 °C, and few results exist also at 26.5 °C which were determined by Chirife and Fontan [150].…”

“…Vapour pressures of water over citric acid solutions, based on measurements from [89,93,144,149] can be represented by the following correlations The corresponding water activities a w can be calculated using Eqs. (2.84).…”

Water activity and activation diameters from hygroscopicity data - Part II: Application to organic species

“…We also show data for glucose and fructose for comparison with our HTDMAderived estimates. Peng et al (2001b) suspended drops of aqueous solutions of glucose at controlled RH in an electrodynamic balance and deduced composition from particle mass measurements. Bhandari and Bareyre (2003) used a water activity meter with a sensitivity of 0.001.…”

“…12. The fit for water activity for glucose solutions suggested by Peng et al (2001b) is not used, as the reported water activity polynomials are only valid for a w <0.98.…”