Investigation of Physiological Properties of Transglycosylated Stevia with Cationic Surfactant and Its Application To Enhance the Solubility of Rebamipide

Abstract

The poor water solubility of rebamipide was enhanced by the mixed micelles of transglycosylated stevia (Stevia-G) and trimethylammonium chloride with varying carbon chain length (C n TAC, n = 14, 16, and 18). Fluorometry, isothermal titration calorimetry (ITC) and dynamic light scattering techniques examined the aggregation properties of Stevia-G and C n TAC. Synergism was found between Stevia-G and C n TAC using the approaches of Clint and Rubingh. The negative interaction parameter (average β m = −4.17, −5.47, and −7.07) and excess free energy (average ΔG° ex = −2.47, −3.06, and −3.88 kJ mol–1) increased with increasing chain length of C n TAC. The negative B 1 values by the Maeda approach suggested that chain–chain interactions contribute to the formation of a mixed micelle. The solubilization of rebamipide in the mixed micelle was evaluated in the term of the molar solubilization ratio (MSR) and partition coefficient (K m). The K m from the Stevia-G/C16TAC system was highest at a low mole fraction of C n TAC (0.2–0.6). In conclusion, the solubilization of rebamipide was more favorable between Stevia-G and C16TAC, although the stability of the mixed micelle was enhanced by an increase in hydrophobicity of the longer chain lengths used in C n TAC.

Tailoring the Self-Assembly of Steviol Glycoside Nanocarriers with Steroidal Amphiphiles

“…For SDS/Stevia-G and SC/Stevia-G mixed micelles, a composition-independent interaction parameter gave a good fit to the CMCs, whereas for SDC/Stevia-G, RST gave a greater departure from the experimental CMCs, likely because of the broad CMC range of SDC (Figure D–F, Table S2 in the SI). Stevia-G had the strongest synergism with SDS (β m = −3.78), in line with that previously measured between Stevia-G and cationic trimethylammonium chlorides with different alkyl chain lengths (14–18 carbons; β m = −4.17 to −7.07) . The larger interaction parameter absolute value of SDC (β m = −2.37) than of SC (β m = −1.18) indicates that the number of hydroxyl groups was pertinent for determining the extent of synergistic interactions with Stevia-G in these two otherwise structurally similar bile salts, namely, a larger number of OH groups led to lower synergism.…”

“…Stevia-G had the strongest synergism with SDS (β m = −3.78), in line with that previously measured between Stevia-G and cationic trimethylammonium chlorides with different alkyl chain lengths (14−18 carbons; β m = −4.17 to −7.07). 30 The larger interaction parameter absolute value of SDC (β m = −2.37) than of SC (β m = −1.18) indicates that the number of hydroxyl groups was pertinent for determining the extent of synergistic interactions with Stevia-G in these two otherwise structurally similar bile salts, namely, a larger number of OH groups led to lower synergism.…”

“…Stevia-G originates from stevioside, extracted from the plant Stevia rebaudiana, well-known as an artificial sweeter . Controlling the hydrophilic–hydrophobic balance of steviol glycosides by modifying the number of sugar groups can readily be used to tailor their surface activity. , This modification enables Stevia-G to exhibit synergistic interactions with anionic and cationic surfactants and form mixed micelles with improved solubilization properties of poorly water-soluble drugs. − However, understanding of the structural properties of steviol glycosides in mixtures with bile salts is still emerging, and further insights are needed to facilitate the determination of design criteria for their nanocarrier applications.…”

Virtual Issue on Surfactants

“…On the other hand, using several spectroscopic techniques, like fluorometry, isothermal titration calorimetry (ITC), and dynamic light scattering, Uchiyama et al have established the aggregation properties of Stevia-G and C n TAC. Additionally, it was found that the solubilization of rebamipide was more favorable between Stevia-G and C 16 TAC, as was measured through the molar solubilization ratio (MSR) and partition coefficient ( K m ) estimation . In terms of theoretical perspective, on the basis of the simulation study, Sharma et al have estimated the self-assembly of multiheaded surfactants in aqueous solutions .…”

“…Additionally, it was found that the solubilization of rebamipide was more favorable between Stevia-G and C 16 TAC, as was measured through the molar solubilization ratio (MSR) and partition coefficient (K m ) estimation. 2 In terms of theoretical perspective, on the basis of the simulation study, Sharma et al have estimated the self-assembly of multiheaded surfactants in aqueous solutions. 3 It was found that the increase in the number of charged head groups affects the aggregation propensity of surfactants in their aqueous solutions.…”