1 research outputs found
Improved Biopharmaceutical Properties of Oral Formulations of 1,2,4-Thiadiazole Derivative with Cyclodextrins: in Vitro and in Vivo Evaluation
The synthesized 1,2,4-thiadiazole
derivative displaying biological
activity has low aqueous solubility and dissolution rate. Novel oral
formulations of thiadiazole with β- and hydroxypropyl-β-cyclodextrins
were obtained by grinding and freeze-drying methods with the purpose
to improve the aqueous solubility. Complex formation of 1,2,4-thiadiazole
derivative with cyclodextrins was confirmed by means of solid-state <sup>13</sup>C MAS CP/TOSS NMR. Solubility, dissolution rate and permeability
of the solid inclusion complexes were evaluated in different biorelevant
media (SGF, FaSSGF, FaSSIF) simulating the conditions in the gastrointestinal
tract. It was demonstrated that the content of biorelevant media affects
the properties of the inclusion complexes. In particular, solubilizing
effect of cyclodextrins became less pronounced when the micelles of
taurocholic acid and lecithin are formed in the dissolution media.
The inclusion of thiadiazole into cyclodextrin cavity is in competition
with its partitioning into the micelles and this should be taken into
account when the in vivo behavior is predicted. The results of in
vitro and in vivo experiments were found to be in agreement and showed
the highest solubility, dissolution rate and bioavailability of the
freeze-dried complexes of thiadiazole with hydroxypropyl-β-cyclodextrin.
These complexes can be proposed as more effective dosage forms for
oral administration