Maria Vikmon

Interaction of Hydroxy Acids with β-Cyclodextrin

The solubility of β-cyclodextrin (β-CD) was studied in aqueous solutions of various organic acids. The hydroxy acids, especially citric and tartaric acid were found to increase the solubility of β-CD, while some other carboxylic acids reduced it. From solubility data the apparent complex association constants were calculated.

Induced circular-dichroism spectra of complexes of cyclomalto-oligosaccharides and azobenzene derivatives

Abstract The circular-dichroism spectra of the inclusion complexes of 9 types of cyclodextrin (CDs) with 6 kinds of azobenzene derivatives generally show a single peak, but sometimes form a splitting pattern in the first π → π* region. All single patterns show a positive sign; indicating that the long and slim azobenzene derivatives are incorporated into the cavity from the long-axis side. The splitting patterns change in sign and magnitude according to the substitution on the component molecules and establish the formation of various stacking modes. Plots of the lengths of the azo dyes vs. the molar circular-dichroism coefficients suggest that the substituent on the CD torus is an important factor in causing splitting and deciding the sign of the split-type Cotton effects. The foregoing splitting may arise from exciton interaction of two molecules of the chromophoric dye each in the form of a 1:1 complex and in the cyclomaltooctaose (γCD) complex.

The terfenadine/β-cyclodextrin inclusion complex

Terfenatine (TFN) is a very hydrophobic antiallergic drug. It exists in three polymorphic and two solvated forms and is practically insoluble in water. These properties make a pharmaceutical formulation with acceptable biopharmaceutical characteristics difficult to prepare. Inclusion complexation with β-cyclodextrin (βCD) may eliminate such problems. The properties of the TFN/βCD system have been studied in liquid, gaseous and solid phases by1H and13C NMR spectroscopy, powder X-ray diffractometry, differential scanning calorimetry and fast atom bombardment mass spectrometry. The solubility phase diagram was also recorded. In solution and in the gaseous phase the 1∶1 complex prevails, whereas a 1∶2 TFN/βCD complex has been isolated by precipitation from homogeneous solution.

Induced circular-dichroism spectra of complexes of cyclomalto-oligosaccharides and azo dyes containing naphthalene nuclei☆

Abstract In the circular-dichroism spectra of inclusion complexes of 7 types of cyclodextrin (CDs) with 6 kinds of azo dyes containing the naphthalene nucleus, the direction of inclusion and the stacking mode may be elucidated from patterns in the u.v. and the first π→π * regions. The patterns in the former region indicate that the naphthalene fragment in almost all of complexes is incorporated equatorially into the cavity. Those azo dyes that have a tight fit in the CD cavity exhibit exciton interaction between two molecules of the chromophoric dye included in the complexes. The spectral pattern changes in sign according to the inclusion mode of the guest molecules and the angle between the chromophores. For example, the spectral pattern of the Orange II-cyclomaltoheptaose (β CD) complex indicates that the naphthalene nucleus is included axially, and that the angle between two molecules of the azo dye is >90°. On the other hand, the spectral pattern of the Croceine Orange-DM-β CD complex indicates equatorial inclusion and a stacking angle of

Complexation of Manidipine with Cyclodextrins and their Derivatives

Manidipine (MDP,(±)-2-[-(diphenylmethyl)-1-piperazinyl]ethylmethyl-1,4-dihydro-2,6-dimethyl-4(m-nitrophenyl)-3,5-pyridinedicarboxylate methyl-ester) is a poorlysoluble (<1 μg/mL) long acting antihypertensive drug. Salt formingwith citric or tartaric acid results in a 400 to 600 fold solubilityenhancement, respectively, which can be further increased by an order ofmagnitude with cyclodextrins. Dimethyl-βCD alone results in a more than8000 fold solubility enhancement. Besides the strongly enhanced solubility1HNMR spectroscopy also proves the inclusion-type interactionbetween Manidipine and cyclodextrins. From the attained 5-8 mg/mL solubilityof the drug in water an improved bioavailability and pharmacokinetics isexpected.

The association of inclusion complexes of cyclodextrins with azo dyes

OrangeII (4) and γ cyclodextrin (CD) form 2 : 1 and 2 : 2 complexes. The complexes self-associate and microscopy indicates the formation of a fibroid aggregate. In the induced c.d. spectrum, the π → π* band of this complex appears at ∼500 nm in solution, but in the aggregate it changes to aJ-band due to the head-to-tail stacking of4 and aH-band due to its parallel stacking; this indicates that the aggregation expands not only in the direction of the symmetry axis of the CD, but also in the other two dimensions.2H-NMR spectroscopy from deuteron exchange and solvation between the aggregate and deuterium oxide exhibits quadrupole splitting in the region of 0–0.2 KHz. The orientation behavior obtained from this splitting suggests the formation of a liquid-crystaloid substance.13C-T1 NMR indicates that molecules4 and γ CD show the sameT1 values even at 333 K; this complex behaves like a single molecule. The behaviors of other azo dye-CD complexes are also discussed.