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it was calculated using the following equation: where, Q s is the cumulative drug permeation per unit area (μg·cm −2 ), C sn is the drug concentration measured in the receptor fluid at n sampling intervals (μg·m·L −1 ), V S is the volume of the receptor pool (13 mL), is the cumulative drug concentration in the receptor fluid, S is the sampling volume (2 mL), and A S is the effective diffusion area (1.0 cm 2 )

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When this happens, the nerve ends become very irritable and can cause severe pain