The aim of this investigation was to develop and optimize bisoprolol fumarate matrix tablets for sustained release application by response surface methodology based on 23 factorial design. The effects of the amounts of calcium alginate, HPMC K4M, and Carbopol 943 in bisoprolol fumarate matrix tablets on the properties of bisoprolol fumarate sustained release matrix tablets like drug release and hardness were analyzed and optimized. The observed responses were coincided well with the predicted values by the experimental design. The optimized bisoprolol fumarate matrix tablets showed prolonged sustained release of bisoprolol fumarate over 6 hours. These matrix tablets followed the first-order model with anomalous (non-Fickian) diffusion mechanism. 1. Introduction Matrix tablets offer a great potential as oral drug delivery system due to their simplicity, cost effectiveness, reduced risk of systemic toxicity, and minimal chance of dose dumping [1, 2]. They exclude complex production procedures such as coating and pelleatization during manufacturing, and drug release rate from the dosage form is controlled mainly by the type and proportion of polymer used in the preparations [3]. Various natural and synthetic hydrophilic polymers have been used in production of matrix tablets for soluble and insoluble drugs for years [1, 4–7]. Hydrophilic matrices are generally made of hydrogels, which have water absorbing capacity and swell to form a gel-like structure [8]. Swollen gel acts as a reservoir which slowly releases the drug dispersed already in the hydrogel matrices. Over the years, the use of polymer combinations as blends to prolong the drug release rate has become more popular, which may allow formulators to develop sustained release dosage forms that may show performance improvements over the individual polymer components [2]. Among various methods of the matrix tablet preparation, direct compression method has attracted much attention due to its technological simplicity and industrial acceptability as it involves simple blending of all ingredients used in formulations followed by compression. Moreover, it requires fewer unit operations, less machinery, reduced number of personnel and reduced processing time, increased product stability, and faster production rate [9]. Bisoprolol fumarate, chemically 1-[4-(2-isopropoxyethoxymethyl)phenoxy]-N-isopropyl-3-aminopropan-2-ol fumarate, is a cardioselective -blocker (Scheme 1) without membrane stabilizing activity or intrinsic sympathomimetic activity [10, 11]. It is used for the treatment of hypertension and
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