ABSTRACT
The implantation of controlled drug release devices represents a new strategy in the treatment of neurodegenerative disorders. Sol-gel titania implants filled with valproic acid, have been used for this purpose to treat induced epilepsy in rats. The kinetics of the drug release depend on: (a) porosity, (b) chemical interactions between valproic acid and surface hydroxyl groups of titania, (c) particle size, and (d) particle size agglomerates. The concentration of water used in the hydrolysis reaction is an important variable in the degree of porosity, hydroxylation, and structural defects of the nanostructured titanium oxide reservoir. The titanium n-butoxide/water ratio was systematically varied during the sol-gel synthesis, while maintaining the amount of valproic acid constant. Characterization studies were performed using DTA-TGA, FTIR, Raman, TEM, SEM, BET, and in vitro release kinetic measurements. The particle agglomerate size and porosity were found to depend on the amount of water used in the sol-gel reaction.
Subject(s)
Anticonvulsants/chemistry , Infusion Pumps, Implantable , Titanium , Valproic Acid/chemistry , Water/chemistry , Anticonvulsants/pharmacology , Particle Size , Porosity , Valproic Acid/pharmacologyABSTRACT
In this study four types of SBAs were synthesized and then impregnated with hydrocortisone. One is a straight SBA-15, obtained using Pluronics P123 as structuring agent; two others were modified using 1,3,5-trimethylbenzene as additive, and the fourth one was prepared using sodium iodide as additive. Three of these have in common a p6 mm symmetry with nanotubes packed hexagonally, yet they differ in their functional groups. The fourth sample is basically disordered. The drug release kinetics showed two stages: a fast-rate early stage dominated by the controlled release of the hydrocortisone adsorbed in the macropores of the reservoir, followed by a slow-rate delivery that we assume is controlled by the hydrocortisone diffusion through the nanopores. It is shown that the release kinetics can be strongly influenced by using different co-additives.