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A high-performance liquid chromatography (HPLC) assay has been developed for the determination of flutamide and its degradation products. Using this method, the influence of important formulation factors on the stability of flutamide has been estimated. The stability studies have been carried out in solid state as well as in aqueous solution. The results obtained have shown a good stability for flutamide in solid state. This drug remained practically unchanged after a four-month assay in adverse temperature and humidity conditions. On the other hand, the results obtained from the stability study in solution during 12 days have shown that flutamide in aqueous solution underwent a clear degradation at mean or high temperature (22 degrees C, 37 degrees C) and acidic pH conditions (1.1). With respect to the influence of ionic strength, it has been found that the presence of sodium chloride prevents the degradation of flutamide in aqueous solution. The second-order kinetics model provides the best fit for highly degraded solutions.

The hydrophilic matrices are one of the most used types of Controlled Release Systems in the world. In comparison with other Controlled Release Devices, they have the advantage of their low cost and simple technology, that facilitates their application to an important sector of the population, as well as their safety against the dose dumping (accidental fast release of the whole drug dose).1) Another advantage of these matrices concerns the drug release kinetics. Using these systems, it is possible to obtain a variety of release kinetics, including in some cases zero-order release kinetics.2)The study of hydrophilic matrices is a difficult task due to its complex and disordered structure. A number of publications have reported studies about the mechanisms of drug release from hydrophilic matrices. [3][4][5][6][7][8][9][10][11] In recent works, our research group has applied the percolation theory to study the release and hydration rate of hydrophilic matrices, in order to contribute to the rationalization of the design of these controlled release systems and to obtain a better knowledge of the processes that occur during the release of the drug. [12][13][14] Percolation Theory is a statistical theory that studies disordered or chaotic systems where the components are randomly distributed in a lattice. This theory has wide application in many scientific disciplines and was introduced by Leuenberger et al. in the pharmaceutical field in 1987 to improve the characterization of solid dosage forms. [15][16][17][18][19] Our research group is employing the percolation theory in order to describe solid forms, in concrete controlled release inert matrix systems. 15,16,[20][21][22][23][24][25][26] One of the most important parameters of percolation theory is the percolation threshold, where there is a maximum probability of appearance of an infinite or percolating cluster of a substance and some properties of the system change suddenly. A cluster is defined as a group of neighboring occupied sites in the lattice and is considered infinite or percolating when it extends from one side to the rest of the sides of the lattice, i.e. percolates the whole system. 27)The application of this theory to study the release and hydration rate of hydrophilic matrices allowed for first time to explain the changes in release and hydration kinetic of swellable matrices type controlled delivery systems. [12][13][14] According to this theory, the critical points observed in dissolution and water uptake studies can be attributed to the existence of excipient percolation thresholds. The knowledge of these thresholds is very important to optimize the design of swellable matrix tablets. Above the excipient percolation threshold an infinite cluster of this component is formed, controlling the hydration and release rate. Below this threshold the excipient does not percolate the system and, as a consequence, the drug release can not be controlled. It has to be emphasized that the infinite cluster of excipient responsible for the drug release contro...