All the complexes have shown 75% inhibition to electroshock. The data obtained in this study are in accordance with previous findings and permeation study. FA and HA were also given to mice to check the antiepileptic potential and found zero inhibition. Thus, our optimized complexes were exhibiting

better performance in crossing blood brain barrier (BBB), which may be attributed to increased solubility, passive diffusion gradient and lesser ionic character. Formation of aggregates in humic material is also well known [40], which may lead to increased local concentration of drug. The permeability of optimized complexes across gut sac was significantly increased (∼2.9–3.8 times) as compared to carbamazepine suspension in water in 24 h (Fig. 13). KU-57788 clinical trial The permeation profile of complex shows two patterns, i.e. in initial 10 h there was a sharp increase in permeation but after that a plateau was observed. Considering the permeation of complexes across the intestinal membrane, two opposing forces (concentration gradient and aggregation of humic substances) act against each other. The one that predominates influences the

result. Initially, permeation increased steeply because there was an increasing concentration gradient across the sac but after sometime (10 h) it attains plateau, as the gradient falls. In spite of having larger size, HA was showing a better permeability in both the methods of complexation because of its structure. In aqueous media HA is less charged [41] and more hydrophobic GSK J4 purchase [31], which aids in its permeation across intestinal mucosa. After ageing freeze dried complexes of HA–CBZ complex (1:1 and 1:2)

and FA–CBZ complex (1:1 and 1:2) showed only single spots. But the position of spots was variable, which may be due to different polarities [25] of complexing agents (HA and FA). Pure CBZ showed the Rf value of 0.5 while the average Rf values for fulvic acid Immune system complexes (1:1 and 1:2) were around 0.6. Average Rf values for humic acid complexes (1:1 and 1:2) were around 0.45. This study indicates the stability of developed complexes during the study. TBARS levels were significantly elevated in PTX-treated group (1.13±0.064 vs. 4.49±0.14) (p<0.01). TBARS levels were also significantly elevated in the CBZ treated group. TBARS levels were significantly decreased to the normal in all the groups treated with the carbamazepine complexes (groups 4–7). F (8, 45)=245.21. Among the entire complexed groups the TBARS levels were effectively normalized with the CBZ–HA (1:2 KD) treated group ( Table 3). Picrotoxin (PTX) treatment significantly enhances the TBARS level compared with the saline control group. This finding is in agreement with earlier findings, which point to the development of oxidative stress in epilepsy.