Employment of Sequential Simplex Method of Optimization in the Development of Fast Dissolving Tablets of Clozapine

Among the various optimization techniques used, one of the simplest is the sequential simplex design. This approach has the in-built advantage of adjusting the levels of the factors to achieve the desired target. This method of optimization uses the results of previous experiments in a mathematically rigorous fashion to define the parameters (i.e. independent variables) for the next experiment in the search for optimum response. The present work aims at employing this technique to develop fast dissolving tablets of clozapine. The tablets were prepared by direct compression which has the advantage of simplicity and efficiency. Microcrystalline cellulose and polyplasdone were selected as the two variables and the formulations were evaluated for responses such as disintegration time, hardness and friability. The success of the formulations was evaluated in terms of a total response equation generated in accordance with the priority of the response parameters. Based on the ranking, the sequence was continued by different approaches such as reflection, expansion or contraction. The sequence was continued until a desirable disintegration time of less than 10 second with adequate hardness was achieved.