Solvent Effects on Chemical Processes. 10. Solubility of α-Cyclodextrin in Binary Aqueous-Organic Solvents: Relationship to Solid Phase Composition

Leiterman, Rachel V.; Mulski, Michael J.; Connors, Kenneth A.

doi:10.1002/jps.2600841103

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…While urea is a well-established co-solute for enhancing CD dissolution, the other neutral species in ethaline or glyceline are not. EG is not a good solvent for β-CD (solubility of ∼20 mg/mL), and only water/EG (20:80) mixtures reach a β-CD solubility of 29 mg/mL (α-CD shows a solubility in EG of ∼70 mg/mL); analogously, GLY has been reported to be a poor solvent for both α- and β-CD . On the other hand, the addition of urea to water (a poor β-CD solvent) allows the β-CD solubility to reach 250 mg/mL (solubility in neat water of 18 mg/mL) and disrupts CD’s aggregates .…”

Section: Resultsmentioning

confidence: 99%

Structural Features of β-Cyclodextrin Solvation in the Deep Eutectic Solvent, Reline

2020

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The inherently amphiphilic nature of native cyclodextrins (CDs) determines their peculiar molecular encapsulation features, enabling applications such as targeted drug nanodelivery, aroma protection, etc. On the contrary, it may also lead to poor solubility in water and other organic solvents and to potentially detrimental flocking in these media, thus posing limitations to more extensive usage. Here we use small angle X-ray scattering to show that deep eutectic solvent reline (1:2 choline chloride:urea) succeeds in dissolving large amounts of β-CD (at least 800 mg/mL, compared with the solubility in water of 18 mg/mL), without aggregation phenomena occurring. At the microscopic level, molecular dynamics simulations highlight the complex interplay of hydrogen bonding-mediated hydrophilic interactions and hydrophobic force mitigation occurring between β-CD and reline components, leading to energetically favorable β-CD solvation. The possibility of achieving very high concentration conditions for unaggregated β-CD in an environmentally responsible media, such as reline, can open the way to new, so far unpredictable applications, addressing multiple societal challenges.

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Section: Resultsmentioning

confidence: 99%

Structural Features of β-Cyclodextrin Solvation in the Deep Eutectic Solvent, Reline

2020

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“…Samples of the solid phase were dried at room temperature to prevent the removal of solvent loosely bound that may affect the thermal behavior. 11 The existence of more than one stable solid phase was observed for R-cyclodextrin in water-ethylene glycol solvent mixtures 12 whereas the crystal form of other drugs remained unchanged in cosolvent-water mixtures. 11 The literature reports two polymorphs for paracetamol, 13,14 form I (mp 168-170°C) and form II (mp 160-161°C).…”

Section: Resultsmentioning

confidence: 99%

Enthalpy–entropy compensation for the solubility of drugs in solvent mixtures: Paracetamol, acetanilide, and nalidixic acid in dioxane–water

Bustamante

Romero

Peña

et al. 1998

Journal of Pharmaceutical Sciences

240

115

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In earlier work, a nonlinear enthalpy-entropy compensation was observed for the solubility of phenacetin in dioxane-water mixtures. This effect had not been earlier reported for the solubility of drugs in solvent mixtures. To gain insight into the compensation effect, the behavior of the apparent thermodynamic magnitudes for the solubility of paracetamol, acetanilide, and nalidixic acid is studied in this work. The solubility of these drugs was measured at several temperatures in dioxane-water mixtures. DSC analysis was performed on the original powders and on the solid phases after equilibration with the solvent mixture. The thermal properties of the solid phases did not show significant changes. The three drugs display a solubility maximum against the cosolvent ratio. The solubility peaks of acetanilide and nalidixic acid shift to a more polar region at the higher temperatures. Nonlinear van't Hoff plots were observed for nalidixic acid whereas acetanilide and paracetamol show linear behavior at the temperature range studied. The apparent enthalpies of solution are endothermic going through a maximum at 50% dioxane. Two different mechanisms, entropy and enthalpy, are suggested to be the driving forces that increase the solubility of the three drugs. Solubility is entropy controlled at the water-rich region (0-50% dioxane) and enthalpy controlled at the dioxane-rich region (50-100% dioxane). The enthalpy-entropy compensation analysis also suggests that two different mechanisms, dependent on cosolvent ratio, are involved in the solubility enhancement of the three drugs. The plots of deltaH versus deltaG are nonlinear, and the slope changes from positive to negative above 50% dioxane. The compensation effect for the thermodynamic magnitudes of transfer from water to the aqueous mixtures can be described by a common empirical nonlinear relationship, with the exception of paracetamol, which follows a separate linear relationship at dioxane ratios above 50%. The results corroborate earlier findings with phenacetin. The similar pattern shown by the drugs studied suggests that the nonlinear enthalpy-entropy compensation effect may be characteristic of the solubility of semipolar drugs in dioxane-water mixtures.

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“…It is important to underline that those tripartite interactions differ from those most studied with host-guest systems (8). In the typical ␤-CD-mediated host-guest complexing, the guest molecules inhabit the cavities of the cyclodextrin host, most often in a 1:1 stoichiometric ratio (10,16). Because free dendrimers or dendrimer/DNA complexes are larger than the diameter of the ␤-CD cavity, dendrimer-DNA-␤-CD interactions are mainly electrostatic and involve charged groups on the surface of the respective molecules.…”

Section: Characterization Of Dendrimer-dna Complexes In the Presence mentioning

confidence: 99%

Substituted β-Cyclodextrins Interact with PAMAM Dendrimer–DNA Complexes and Modify Transfection Efficiency

Roessler

Bielinska

Janczak

et al. 2001

Biochemical and Biophysical Research Communications

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Solvent Effects on Chemical Processes. 10. Solubility of α-Cyclodextrin in Binary Aqueous-Organic Solvents: Relationship to Solid Phase Composition

Cited by 12 publications

References 19 publications

Structural Features of β-Cyclodextrin Solvation in the Deep Eutectic Solvent, Reline

Structural Features of β-Cyclodextrin Solvation in the Deep Eutectic Solvent, Reline

Enthalpy–entropy compensation for the solubility of drugs in solvent mixtures: Paracetamol, acetanilide, and nalidixic acid in dioxane–water

Substituted β-Cyclodextrins Interact with PAMAM Dendrimer–DNA Complexes and Modify Transfection Efficiency

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