CONICET | Buscador de Institutos y Recursos Humanos

Cyclodextrins are cyclic oligosaccharides capable of include poorly soluble drugs in their hydrophobic cavity. Thus, inclusion complexes are formed and help to increase the water solubility of drugs and their bioavailability. Chitosan (CHT) is a natural polymer widely used in the preparation of delivery systems to achieve a controlled and targeted administration of active ingredients. Moreover CHT liquid solution responds to temperature changes: near to human body temperature a CHT liquid solution turns into a gel state. Progesterone (PGT) is a natural hormone with low aqueous solubility that is used in hormonal therapies, both in animals and humans. To improve the drug application a ternary system consisting of PGT-methylated β-cyclodextrin-CHT gel was prepared and characterized. PGT-randomly methylated β-cyclodextrin inclusion complexes were obtained by freeze-dried method. Complex formation was verified by IR and H-RMN experiments. In addition, apparent stability constant and complexation efficiency were estimated (35504 M-1 and > 90%, respectively). Subsequently, CHT gels containing free and complexed PGT were prepared. In vitro drug release experiments were performed in PBS-SDS (pH: 7.4) at 37 ºC. Aliquiots were withdrawn at predetermined times intervals and assayed by HPLC. An equal amount of fresh medium was added to maintain a constant volume. The transition of CHT solutions from liquid to gel state was not affected by the presence of free or complexed PGT, since the gelling time was not modified in comparison with CHT solution without drug. In addition, the gel with drug presented a good macroscopic consistency. Results demonstrated that complexed PGT is more water soluble than free PGT. In addition, controlled release of PGT from CHT gels can be reached by using inclusion complexes with cyclodextrin.