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J. Phys. Chem. B 2006, 110, 10190-10196
Role of Deliquescence Lowering in Enhancing Chemical Reactivity in Physical Mixtures Adnan K. Salameh and Lynne S. Taylor* Industrial and Physical Pharmacy, School of Pharmacy, Purdue UniVersity, West Lafayette, Indiana 47907 ReceiVed: February 27, 2006; In Final Form: March 31, 2006
Mixtures of deliquescent solids are susceptible to deliquescence lowering, where water vapor condensation occurs in mixtures at a lower critical relative humidity (RH0mix) than individual component critical relative humidities (RH0s). The purpose of this study was to evaluate the effect of deliquescence lowering on chemical reactivity. Sucrose, citric acid and their physical mixtures were characterized using vapor sorption analysis to determine RH0 and RH0mix. Acid-catalyzed sucrose hydrolysis kinetics was determined using polarimetric analysis. Physical mixtures of sucrose and citric acid crystals were prepared and stored at various relative humidities at 22 °C. For these physical mixtures, sucrose hydrolysis was found to occur only when the environmental RH exceeded RH0mix. Degradation kinetics correlated with the storage RH, being fastest at higher RH. In addition, a lag period was initially observed, which was most prominent for samples stored close to RH0mix. With exposure to RHs below RH0mix, no sucrose degradation was detected over the experimental time period. In conclusion, mixtures of deliquescent solids showed increased water sorption at lower RHs, which caused solid dissolution and subsequently led to an increase in the chemical reactivity.
Introduction Many systems of biological relevance including food, pharmaceutical, nutraceutical, and agrochemical products are prone to chemical instabilities where various types of degradation pathways can occur both in solution and in the solid state. Examples of typical reactions include oxidation,1,2 cyclization,3 deamidation,4,5 hydrolysis,6,7 and the Maillard reaction.6,8,9 Molecular mobility is a key parameter in influencing chemical reactivity,3,10 and consequently reactions generally occur more readily in solution and disordered solids than in well-ordered crystalline phases.11 The reactivity of solids can also be affected by atmospheric water,12-15 where water can function as a reactant, as a product, as a reaction medium, or by enhancing molecular mobility at disordered sites.15,16 Deliquescence, a phenomenon exhibited by many highly water soluble crystalline solids, leads to the production of bulk liquid water in solid systems via vapor condensation at relative humidities (RHs) less than 100% RH. At low RHs, deliquescent solids adsorb minimal surface moisture due to hydrogen bonding.17 When the ambient RH exceeds a critical relative humidity that is specific to the compound (RH0), the solid sorbs significant amounts of water and commences dissolution until a saturated solution is reached.18,19 As RH is further increased, more vapor condensation occurs and dilution ensues. It is clear that if a labile organic material undergoes deliquescence, chemical stability is likely to be compromised. Deliquescence is a property exhibited by a variety of diverse compounds including some inorganic salts, sugars, organic acids, vitamins, and drugs.20-24 Since deliquescence can potentially compromise physical and chemical integrity, susceptible compounds need to be shielded from relative humidities that exceed RH0. In this context, it is important to consider the phenomenon of deliquescence lowering whereby the solid-solution transformation occurs at a lower RH when there is physical contact * Address correspondence pharmacy.purdue.edu.
to
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author.
E-mail:
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between two or more deliquescent compounds. Deliquescence lowering is a well-established phenomenon that was first reported to occur in fertilizers composed of inorganic salt mixtures,25 and has also been observed in atmospheric aerosols as well as for food and pharmaceutical systems.24,26-29 The deliquescence point of a mixture (RH0mix) is dependent on the individual RH0 values and can often be approximated by the product of the water activities of a saturated solution of each component.26,30 Despite the widespread use of deliquescent compounds in organic composites (foods, pharmaceuticals, multivitamin preparations, etc.), the consequence of deliquescence lowering on product functionality has received scant attention. The goal of this study was to investigate chemical reactivity in a system that was susceptible to deliquescence lowering. Acid-catalyzed inversion of sucrose was chosen as the model chemical reaction. Sucrose inversion (hydrolysis to glucose and fructose) has been studied extensively6,7,31 in part because of the well-known reaction between the hydrolytic products (which are reducing sugars) and primary and secondary amines (found in foods, proteins, pharmaceuticals, and other bioactive ingredients).6,7,9,31-33 In the presence of acidic species, sucrose hydrolysis is known to proceed even at very low moisture levels.6,7 Preliminary work has shown that mixtures of sucrose and citric acid experience a significant deliquescence lowering effect. It was therefore hypothesized that sucrose inversion kinetics would be enhanced in citric acid:sucrose physical mixtures stored at certain relative humidities because of (1) the presence of citric acid as a source of protons and (2) the increased water sorption at a reduced RH due to deliquescence lowering. Materials and Methods Crystalline sucrose, β-D-fructose, R-glucose monohydrate, and citric acid anhydrous were obtained from Sigma Co. (St. Louis, MO). All compounds were used as supplied except for sucrose which, due to its large crystal size (>600 µm), was lightly ground using a mortar and a pestle. Ground sucrose was sieved,
10.1021/jp0612376 CCC: $33.50 © 2006 American Chemical Society Published on Web 05/04/2006
Deliquescence Lowering and Chemical Reactivity and the mesh fraction between 40 (425 µm) and 50 (300 µm) was used in the studies. Saturated salt solutions were used to control RH. The following saturated salt solutions were used: potassium carbonate (43% RH), magnesium nitrate (54% RH), sodium nitrite (65% RH), strontium chloride (71%), sodium chloride (75% RH), and potassium chloride (85% RH).34 Dynamic Vapor Sorption. The critical relative humidity of deliquescent solids (RH0) and mixtures (RH0mix) can be obtained from their vapor sorption data.24 Gravimetric sorption analysis was performed using a Symmetrical Gravimetric Analyzer (SGA-100) (VTI Corporation, Hialeah, FL) at 25 °C. A sample size of 20-25 mg was used. For the mixtures, which were prepared at a 50:50 wt % ratio, individual components were weighed and mixed in the SGA sample holder and the entire sample was used for analysis. Prior to sorption, samples were dried at 50 °C in the sorption analyzer. No drying step was carried out for samples containing glucose monohydrate. The settings for the sorption analyzer were as follows: equilibrium criterion for the drying step was 0.01% w/w in 2 min, the maximum drying time was 60 min, and the step equilibrium criterion was 0.01% w/w in 15 min with a maximum step time of 90 min. During the experiment, the sample was exposed to increasing RH, and two to three data points were collected below and above RH0. RH0 and RH0mix were determined by extrapolating the linear parts of the moisture sorption data before and after the deliquescence event.24 Water Activity Measurements. Water activities (aws) of saturated solutions of single-component and multicomponent systems were measured at 25 °C using a chilled mirror dewpoint instrument (AquaLab 3TE, Decagon, Pullman, WA). Saturated solutions were prepared by mixing approximately 4 g of the physical mixture (prepared by geometric mixing) with small amounts of double distilled water (∼250-500 µL). To ensure the attainment of a saturated solution with respect to all the solids, aw measurements were obtained after 24 h equilibration time in the AquaLab unit. Sample Preparation and Chemical Reactivity Kinetics Monitoring. Physical mixtures of sucrose and citric acid were prepared by geometric mixing of the crystalline powders in 20 mL glass vials. The total sample weight was 2 g ((1-2% w/w), and the composition was 50:50% w/w sucrose:citric acid. Open sample vials were stored in desiccators at 43, 54, 65, 71, 75, and 85% RH and 22 °C. Sucrose inversion kinetics was studied in solution at two different sucrose:citric acid concentrations: 10% w/v and 33% w/v solutions were prepared by dissolving 10 and 33 g each of sucrose and citric acid anhydrous in double distilled water and the volume was adjusted to 100 mL. Control samples composed only of crystalline sucrose were stored at 71 and 85% RH. Sucrose inversion kinetics was monitored using polarimetry.35 Duplicate samples were removed from each desiccator at various time points, and double distilled water was added to dissolve the solids. When the solids were completely dissolved, the vial contents were transferred to a 10 mL volumetric flask and the volume was adjusted to 10 mL to produce a 10% w/v solution. Sucrose hydrolysis results in glucose and fructose moieties. Upon the addition of water, fructose mutarotates relatively quickly35 and the optical rotation of the solution changes with time until it reaches an equilibrium value after about 2-3 h. Solutions were therefore left on the bench at 22 °C for 2-3 h before analysis to correct for fructose mutarotation.7 To measure optical rotation, a Perkin-Elmer Model 241 Polarimeter (Perkin Elmer, Shelton, CT) was used with a standard cell and sodium lamp as a light source. The amount of sucrose remaining was
J. Phys. Chem. B, Vol. 110, No. 20, 2006 10191
Figure 1. Moisture sorption data of sucrose and citric acid anhydrous, and a 50:50% w/w physical mixture at 25 °C.
measured using the following equation:36
x)
Rs - R Rs - Ri
(1)
where Rs is the specific rotation of a 100% sucrose sample, which is calculated to be 66.4;36 Ri is the specific optical rotation of 100% invert sugar, which is equal to -19.7;37 and R is the specific optical rotation of the test solution, which can be calculated from the equation
R)
100Rc LCs
(2)
where Rc is the polarimeter reading, L is the length of the cell in decimeters, and Cs is the sample concentration in solute grams per 100 mL of the solution.38 Polarimetric analysis showed good repeatability as evidenced by the minimal variability in the extent of sucrose hydrolysis between duplicate samples (
