584 (Fig. 11), which is more stable as CBZ alone. Energy optimization of carbamazepine resulted in −6.84 kcal/mol. In this complex H of amide of CBZ
has an H-bond with OH of HA. Carbamazepine is see more practically insoluble in water, aqueous saturation solubility of carbamazepine was found to be 12.65 μg/ml. Complexation of carbamazepine greatly increased the solubility (Table 1). Again by all the methods, freeze drying turns out to be a better technique and 1:2 ratio a better option. It was assumed that size of the complexes was less than 0.22 μm as it was the size of “Millipore” filter. Better performance of 1:2 ratios may be credited to the development of CMC in the aqueous media. Because in a similar study [33], CMC of humic acid like substances was found to form micelles at a concentration of 2 g/L. This work also reports the amount of drug solubilized by per gram of HA like substances, which is in accordance with our findings. Here fulvic acid appears to leave a more pronounced effect on the solubility of the drug. GSK1120212 in vitro Humic substances offer both types of interaction like metal ion interaction due to the presence of various functional groups and inclusion of hydrophobic moieties [34] and [35]. Regarding the different binding capacities of HA in comparison
with FA, it is evident from literature that HA binds the model chemicals more than FA. There is roughly a tenfold decrease moving from humic acid samples to fulvic acid samples [25]. But our finding regarding the increased solubility Selleckchem Abiraterone of a hydrophobic substance shows a different result. The reason may be the fact that the sorption/complexation of humic substances is not its intrinsic property; it generally depends on pH values [36] and [37] and on the presence of other ions [38]. As on different pH ranges these
behave differently. The release profiles of pure carbamazepine and complexes, prepared by different methods studied for 60 min, are shown in Fig. 12A and B. Active pharmaceutical ingredients have an intrinsic dissolution rate that is dependent on its solubility and particle size [39], which was showing 34% in 60 min and attaining plateau then after. Among all the methods freeze drying and kneading were performing the best release (∼80%). Maintaining the results of previous findings 1:2 ratio bestowed better. Release profile of humic acid complex was little better than that of fulvic acid. Among the different techniques employed the physical mixture method appears to be complexing the least. We could conclude that better complexing interaction resulted in higher aqueous concentration in a given time period. The result corroborates the data obtained from solubility analysis and different instrumental analyses (Figs. 3–6). From all the previous mentioned studies it was very much obvious that the complexes developed by kneading and freeze-drying methods showed promising results. So, these were chosen for further pharmacodynamic study (Table 2).