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The purpose of the present study was to apply a D-optimal generated response-surface mixture design to the development of extended-release matrix tablets, in order to obtain a specifically targeted drug release, where formulation constraints exist. Bumetanide (CAS 28395-03-1) and magnesium stearate were incorporated into matrix tablets with other ingredients, whose proportions were varied according to D-optimal run specifications. The design-specified powder blends were compressed on a Manesty D3B rotary tablet press. The resultant tablets were dissolution tested and the percent bumetanide release at 1, 4, 8, and 12 h were evaluated as the model responses. Statistical models describing the effects of the causal formulation factors on bumetanide release were developed, and a computer-generated for-mulation prediction based on the constructed models was used to determine which type and proportion of excipients would be required to obtain the targeted release profile. The designed tablet formulation was dissolution tested and the amount of bumetanide released at 1, 4, 8, and 12 h was determined. Employing the model-independent approach using the similarity factor (f2), the optimized dissolution profile was found to be similar to the targeted dissolution profile. It was concluded that D-optimal response-surface mixture experiments could be applied to obtain specific extended-release profiles.