Chem. Pharm. Bull. 54(5) 598—602 (2006)

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). 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. 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. 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. 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. Our research group is employing the percolation theory in order to describe solid forms, in concrete controlled release inert matrix systems. 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. 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. 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 control must be present before the matrix is placed in the dissolution medium, i.e., before the swelling process starts. Lobenzarit disodium is a drug conceived for the treatment of rheumatoid arthritis. This drug produces an improvement of immunologic abnormalities and has a regulatory effect upon the antibody producing system. Its is administered orally in form of tablets and its daily dosage is 240 mg (80 mg three doses per day). According to its pharmacokinetic and dosage characteristics and to the results obtained from the preformulation study carried out by our research team, it is a suitable candidate for the design of controlled release delivery systems. The design of oral controlled release systems of lobenzarit disodium would present the advantage of less frequent dosing. This fact is very important in the case of a chronic disease, as is the rheumatoid arthritis. 598 Vol. 54, No. 5 Chem. Pharm. Bull. 54(5) 598—602 (2006)