Interaction of Native Cyclodextrins and Their Hydroxypropylated Derivatives with Carbamazepine in Aqueous Solution. Evaluation of Inclusion Complexes and Aggregates Formation.

ABSTRACT: A detailed comprehensive study on how the formation of soluble and insoluble carbamazepine/cyclodextrins (CBZ/CD) complexes (with consequent changes in the solid-phase composition) depends on the CD structure is not yet available. Moreover, the study of possible influence of this drug on the tendency of CDs and their complexes to self-aggregate is still lacking. Phase-solubility studies demonstrated that CDs and CBZ form a range of soluble (AL-type: ?CD, ?CD, and hydroxypropylated CDs) and insoluble (BS-type: ?CD) complexes depending on CD used. HP?CD proved to be the best CD solubilizer for CBZ forming the most stable complex with highest apparent solubility, whereas ?CD was shown to be the best native CD. For the native CDs, CBZ solubilization increases with increasing CD cavity diameter (?CD ? ?CD < ?CD). Solid phases collected from phase-solubility studies were characterized by Fourier-transformed infrared spectroscopy, differential scanning calorimetry, and X-ray powder diffraction to elucidate their composition and crystalline structure. They provided similar conclusions being overall supportive of phase-solubility, osmolality, and permeation studies results. Solid CBZ was the only detected component for AL-type profiles over the CD concentration range studied, whereas precipitation of poorly soluble CBZ/?CD complexes (BS-type) was observed (i.e., at and beyond plateau region). Osmometry and permeation studies were applied to evaluate the effect of CBZ on the aggregate formation and also to elucidate their influence on CD complex solubility and permeation profile. Permeation method was shown to be the most effective method to detect and evaluate aggregate formation in aqueous ?CD and HP?CD solutions containing CBZ. CBZ did not affect the HP?CD tendency to self-aggregate but CBZ did modify the aggregation behavior of ?CD decreasing the apparent critical aggregation concentration value from 4.2% (w/v) (in pure aqueous ?CD solution) to 2.5% (w/v) (when CBZ was present).

SUBMITTER: Rodrigues Sa Couto A 

PROVIDER: S-EPMC6648831 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature