## 3 Results  
### Degradation of Individual Pharmaceutical Compounds by the Ascomyce P. oxalicum at Flask-Scale  
Figure 1 represents the results of the individual elimination of each drug tested in this work expressed as global removal rate considering the final time and final residual concentration (the data have a normal distribution according to the normality test, \(p>0.05\)). Under the selected experimental conditions _P. oxalicum_ completely degraded APAP and IBU (4.17 uM/h both, 100%), as well as DFC (2.08 uM/h, 100%) at 24-48 h, corroborating our previous DFC report [19]. In addition, partial degradation of NPX (0.58 uM/h, 70%) and KET was observed, with the latter compound being the most recalcitrant of the evaluated compounds (approximately \(<\)15% of the removal rate in 120 h). The statistical analysis corroborated the results. The biomass, pH and glucose concentration did not show significant changes. Figure 1: Individual degradation at flask-scale: pH and glucose concentration of the tested pharmaceutical compounds by _Pentiillium oxalicum_ in relation to biodegradation of the drugs. (**a**) Diclofenac (DFC); (**b**) ibuprofen (IBU); (**c**) ketoprofen (KET); (**d**) naproxen (NPX); and (**e**) acetaminophen (APAP). Biotic control corresponds to a heat-killed biomass control. The values are presented as the average of three independent experiments \(\pm\) standard deviation (\(n=3\)). Asterisks (*) indicates statistical significance differences using Tukey’s test (\(p<0.05\)). Analysis of Biodegradation Rates from a Complex Mix of NSAIDs/Analgesic Drugs by Penicillin oxalicum under Increasing Glucose Concentration  
NSAIDs and analgesic removal from a complex mix is shown in Figure 2. According to the previous results, we hypothesized that degradation of a complex mixture would require supplementation of glucose to reach 100% of elimination. In this context, the biodegradation of APAP and IBU as part of this mixture were not affected by the addition of glucose into the media and were similar to the results in Section 3.1 (Figure 1). However, a significant decrease of DFC removal rate was observed in the system without glucose supplementation compared to the results observed in individual biotransformation, with total elimination of this compound in the complex mix not achieved, even by 168 h. NPX and KET removal rates had similar results. In contrast, an improvement in the removal rate of DFC, NPX and KET was observed in the feed system, suggesting that glucose concentration has a key role in the biodegradation of mixtures of pharmaceutical compounds by this fungus. The changes in pH and glucose depletion can be observed in the supplementary material (Figure S1). The statistical analysis (Table 1) demonstrated that the supplementation of 3 g/L of glucose positively influences the biodegradation of DFC, KET and NPX and not affected the degradation of IBU and APAP, as previously mentioned. The comparison was made to determine the effect of the addition of glucose in each pharmaceutical compound, no comparison was made between them. Pellets of P. oxalicum Degrade a Complex Mix of NSAIDs/Analgesic in a Batch Fluidized Bioreactor with Glucose Supplementation  
The results of scaling-up the transformation of NSAIDs/analgesic at bioreactor bench scale by the selected model fungus are shown in Figure 3. At bioreactor scale, almost all of the pharmaceutical compounds were eliminated at 192 h, with traces of KET at this time. Deviations in the concentration of the compounds in the initial stage of the experiment can be caused by phenomena of biosorption and desorption due to the stabilization of the system. According to the results shown in Section 3.2, glucose addition was necessary for the treatment of the medium added with a mixture of drugs: the reason why only the feed system was scaled-up. Increases of glucose consumption were observed  
Figure 2: Biodegradation of a complex mix of non-steroidal anti-inflammatory drugs (NSAIDs)/analgesic by _Penicillin oxalicum_ at flask-scale.