Grânulos de Alginato de cálcio como sistema de liberação para um candidato a fármaco derivado do tiofeno

Abstract

The use of biodegradable polysaccharides in development of new drug delivery systems has gained much acceptance. The granules of hydrogels containing a therapeutic agent formed from the sodium alginate polymer in the presence of divalent ions are studied as a multiparticulate system for controlled release site specific, to protect the drug from adverse conditions and to improve its manufacture. The great majority of the substances used in actual therapeutic derived from the utilization of molecular modification, and the heterocyclic compounds that present sulfur atoms in its composition are the target of this strategy, since they exhibit antibacterial, antifungal, antiviral and antitumor activities. The thiophene derivatives containing the cycloalkyl group linked to the ring thiophenic present important pharmacological activities, mainly antifungal activities, being considered important molecules due the increasing demand for new drugs with this activity, but they have limited pharmacokinetic properties owing to its highly hydrophobic character. This study aimed to obtain a multiparticulate system of calcium alginate beads containing 2-[(2, 4-dichlorobenzylidene)-amino]-5,6-dihydro-4H-cyclopentyl[b]thiophene-3-carbonitrile

(5CN06LSVM),

a derivative thiophenic, by ionotropic gelation method from aqueous solution of sodium alginate 3% and O / W emulsion drug 0.1%, mixed in 5 different ratios (A, B, C, D and E) with solution of calcium chloride 10%. The morphology, the scanning electron microscopy (SEM), the yield of the granules, the loading rate, swelling and erosion and the thermal analysis were evaluated. The resulting granules, with the exception of sample B, were oval, not agglomerated and with a surface fissures. The yield ranged between 82% and 107%. The highly hydrophobic compound can be entrapped within the granules. The granules showed low degree o swelling in the simulation solution of gastric juice, but in phosphate buffer pH 7.4 swelled quickly with complete erosion of the polymer network in 60 minutes. The thermo gravimetric analyses showed that thermal stability of the drug was better when incorporated into the granules. I was concluded from this study, it is possible to obtain multiparticulate system using a simple, easy, and reproducible method, can be used for oral administration of hydrophobic drugs.