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Introduction: Generally, the development of microemulsions (MEs) is based on trial and error methods. To obtain the appropriate MEs for transdermal drug delivery with simultaneously desirable physicochemical characteristics including high skin permeation, high stability and high safety. Therefore an optimization process based on computer program is an alternative method to apply in the development of MEs. Materials and Method: The model MEs were prepared according to the ME region obtained from the pseudo-ternary phase diagram. Using simplex lattice design as a model experimental design, the MEs were experimentally formulated and investigated. The ME systems were formulated with oleic acid, Cremophor® RH40, ethanol, water and meloxicam, and their physicochemical characteristics (e.g., droplet size, charge, conductivity, pH, drug loading capacity) and skin permeation flux were evaluated. The ME’s compositions and the physicochemical characteristics were defined as formulation factors (Xn) and response variables (Yn), respectively. The relationship between formulation factor and physicochemical characteristics was investigated using Design Expert® program. Results: The response surfaces estimated by Design Expert® program exhibited obvious relationship between formulation factor and physicochemical characteristics. The formulation factor directly affected the physicochemical characteristics of MEs. The complicated relationship between formulation factor and physicochemical characteristics was clarified using the response surface method. Conclusion: The response surface method was beneficial for the development of MEs for transdermal drug delivery. Using the response surfaces, the physicochemical characteristics of MEs can be predicted without experimentally formulated and characterization.
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