Biodegradation of pharmaceuticals active compounds (PACs) in secondary effluents by using B. subtilis 2012WTNC as a function of β-lactamase was optimized using response surface methodology (RSM) designed by central composite design (CCD). Four factors including initial concentration of bacteria (1-6 log10 CFU mL-1), incubation period (1-14 days), incubation temperature (20-40 °C) and initial concentration of PACs (1-5 mg L-1) were investigated. The optimal operating factors for biodegradation process determined using response surface methodology (RSM) was recorded with 5.57 log10 CFU mL-1 of B. subtilis, for 10.38 days, at 36.62 °C and with 4.14 mg L-1 of (cephalexin/amoxicillin) with R2 coefficient of 0.99. The biodegradation was 83.81 and 93.94% respectively. The relationship among the independent variables was significant (p
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