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The use of optimization techniques employing design of experiments (DoE), however, permeated the field of pharmaceutical product/process development around four decades ago. The first literature report on the rational use of optimization appeared in 1967, when a tablet of sodium salicylate was optimized using a factorial designs (FD). Since then, these systematic approaches have been put into practice in the development of drug formulations at steady pace. Despite tremendous advancements in diverse drug delivery approaches, the oral route remains the most “natural” route of drug administration. In addition, because of the low cost of oral therapy, ease of administration, and improved patient compliance associated with oral route, more than 50% of drug delivery systems available commercially are oral ones.