Estudo da inclusão molecular de produtos de interesse farmacologico utilizando ciclodextrinas

AUTOR(ES)
DATA DE PUBLICAÇÃO

1994

RESUMO

Praziquantel is a potent anthelmintic orally. It has a low aqueous solubility (40mg/ 100ml at 25°C), posing problems in the development of a suitable oral formulation and in the biovailabity of these formulations. In order to solve this difficulities, the microencapsulation with cyclodextrin, named molecular inclusion appeared as a suitable solution as cyclodextrins are now currently being used in laboratory and industry in the microencapsulation of pharmaceutical, aromatic and sensitive substances to control their release and biovailability and to extend their shelf life. Praziquantel (PZ) was found to form an inclusion complex with b-cyclodextrin, hydroxypropyl-b-cyclodexrin and g-cyclodextrin in aqueous solution and the solid state. Complex formation in aqueous solution was studied using phase solubility, spectral and H-NMR methods, while, in the solid state differential scanning calorimetry and scanning electron microscopy were the preferred methods. Phase solubility diagrams of praziquantel/ cyclodextrin complexes showed no deviation from linearity, indicating the presence of one-to-one complex between praziquantel and cyclodextrins. Using the spectra method the formation constant for the 1:1 inclusion complexes were determined to be 101.1M (hydroxypropyl-b-cyclodextrin) and 1.4M (g-cyclodextrin). A solid inclusion complex of PZ with b-CD, b-CDHP and g-CD was prepared using techniques of lyphilization, kneading and co-precipitation. These solid complexes, showed improved dissolution profiles in water compared with the free drug. Dissolution profiles of tables with and without the drug were also obtained using a rotaing basket apparatus.Thermal and oxidation stability of these tablets were examined using differential scanning calorimetry. No significant differences were observed in the thermograms obtained before and after the test, demonstraing the complex stability under thermic and oxidizing conditions. Qualitative tests were carried out with two further drugs in order to observe their affinity to cyclodextrin complexation. Chlorambucil, an antineoplastic agent showed good complexation characteristics with hydroxypropyl-b-cyclodextrin while cephradine showed a better comple - xation characteristic in the g-cyclodextrin cavity. These observations were made after studying the differential scanning calorimetry thermograms.

ASSUNTO(S)

farmacologia cidodestrinas drogas - analise

ACESSO AO ARTIGO

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